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Aim: Aging is related to deterioration of bodily and neural functions, leading to various disorders and symptoms, including the development of dementia, hearing loss, or tinnitus. Understanding how these phenomena are intertwined and how aging affects those is crucial for prevention and the future development of interventions., Methods: We utilized the UK Biobank which includes a total of 502,382 participants between 40 and 70 years old. We used logistic regression models and cox proportional hazard models and compared hazard ratios., Results: The odds of reporting tinnitus in the older age group (i.e., older than 58 years) were increased by 53.6 % and a one decibel increase in the speech-reception thresholds enhanced the odds for tinnitus by 13.0 %. For our second analysis regarding hearing loss, the risk of dementia increased by 14.0 % with an increase by one decibel in the speech-reception threshold score. In terms of aging, each additional year increased the risk by 17.3 %. Tinnitus alone showed a significant influence with a hazard ratio of 52.1 %, however, when adding hearing loss, age and various covariates, the effect vanished., Conclusion: Findings confirm that tinnitus is indeed related to aging, but presumably independent of the aging processes accompanying the development of dementia. This highlights the urge to further investigate the impact of aging on neural processes that are relevant for alterations in the auditory systems (e.g., leading to the development of tinnitus or hearing loss) as well as for increased vulnerability in terms of neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and endocrine glands on the brain, accumulating data suggest that dysfunction of other organs, such as gut, liver, kidney and lung, substantially affects the development and clinical manifestation of age-related brain pathologies. In this Review, a framework is provided to indicate how organ dysfunction can alter brain homeostasis and promote neurodegeneration, with a focus on dementia. We delineate the associations of subclinical dysfunction in specific organs with dementia risk and provide suggestions for public health promotion and clinical management., (© 2024. Springer Nature Limited.)

Parvalbumin-positive (PV+) basket neurons are fast-spiking, non-adapting inhibitory interneurons whose oscillatory activity is essential for regulating cortical excitation/inhibition balance. Their dysfunction results in cortical hyperexcitability and gamma rhythm disruption, which have recently gained substantial traction as contributing factors as well as potential therapeutic targets for the treatment of Alzheimer's Disease (AD). Recent evidence indicates that PV+ cells are also impaired in Frontotemporal Dementia (FTD) and Dementia with Lewy bodies (DLB). However, no attempt has been made to integrate these findings into a coherent pathophysiological framework addressing the contribution of PV+ interneuron dysfunction to the generation of cortical hyperexcitability and gamma rhythm disruption in FTD and DLB. To fill this gap, we epitomized the most recent evidence on PV+ interneuron impairment in AD, FTD, and DLB, focusing on its contribution to the generation of cortical hyperexcitability and gamma oscillatory disruption and their interplay with misfolded protein accumulation, neuronal death, and clinical symptoms' onset. Our work deepens the current understanding concerning the role of PV+ interneuron dysfunction across neurodegenerative dementias, highlighting commonalities and differences among AD, FTD, and DLB, thus paving the way for identifying novel biomarkers and potential therapeutic targets for the treatment of these diseases., Competing Interests: Declaration of Competing Interest ES and GK are scientific co-founders and SR is in the scientific advisory board of Sinaptica Therapeutics. ES is a scientific advisor for BottNeuro AG. HH declares no competing financial interests related to the present article. This work was initiated during his academic appointment at Sorbonne University, Paris, France, and reflects his opinion entirely and exclusively. He is an employee of Eisai Inc. The present article has been initiated and prepared as part of his academic position at Sorbonne University, Paris, France, and reflects his opinion entirely and exclusively. He served as Senior Associate Editor and currently as Reviewing Editor for the Journal Alzheimer’s & Dementia., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Cognitive impairment in Parkinson's disease (PD) can show a very heterogeneous trajectory among patients. Here, we explored the mechanisms involved in the expression and prediction of different cognitive phenotypes over 4 years., Methods: In 2 independent cohorts (total n = 475), we performed a cluster analysis to identify trajectories of cognitive progression. Baseline and longitudinal level II neuropsychological assessments were conducted, and baseline structural magnetic resonance imaging, resting electroencephalogram and neurofilament light chain plasma quantification were carried out. Linear mixed-effects models were used to study longitudinal changes. Risk of mild cognitive impairment and dementia were estimated using multivariable hazard regression. Spectral power density from the electroencephalogram at baseline and source localization were computed., Results: Two cognitive trajectories were identified. Cluster 1 presented stability (PD-Stable) over time, whereas cluster 2 showed progressive cognitive decline (PD-Progressors). The PD-Progressors group showed an increased risk for evolving to PD mild cognitive impairment (HR 2.09; 95% CI 1.11-3.95) and a marked risk for dementia (HR 4.87; 95% CI 1.34-17.76), associated with progressive worsening in posterior-cortical-dependent cognitive processes. Both clusters showed equivalent clinical and sociodemographic characteristics, structural magnetic resonance imaging, and neurofilament light chain levels at baseline. Conversely, the PD-Progressors group showed a fronto-temporo-occipital and parietal slow-wave power density increase, that was in turn related to worsening at 2 and 4 years of follow-up in different cognitive measures., Interpretation: In the absence of differences in baseline cognitive function and typical markers of neurodegeneration, the further development of an aggressive cognitive decline in PD is associated with increased slow-wave power density and with a different profile of worsening in several posterior-cortical-dependent tasks. ANN NEUROL 2024;96:981-993., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these outcomes., Methods: The Sydney Memory and Aging Study included 1037 community-dwelling individuals aged 70-90 years, recruited from Sydney, Australia. Baseline data was collected in 2005-2007 and the cohort was followed for seven waves until 2021. cSBP load was calculated as the area under the curve (AUC) for SBP ≥140 mmHg divided by the AUC for all SBP values. Cumulative diastolic BP (cDBP) and pulse pressure (cPP) load were calculated using thresholds of 90 mmHg and 60 mmHg. Cox and mixed linear models were used to assess associations., Results: Of 527 participants with both seated and standing BP data (47.7% men, median age 77), 152 (28.8%) developed dementia over a mean follow-up of 10.5 years. Higher cPP load was associated with a higher risk of all-cause deaths, and cSBP load was associated with a higher risk of cardiovascular deaths in multivariate models ( P for trend < 0.05). Associations between cPP load, dementia and cognitive decline lost statistical significance after adjustment for age. Differences between sitting and standing BP load were not associated with the outcomes., Conclusion: Long-term cPP load was associated with a higher risk of all-cause deaths and cSBP load associated with a higher risk of cardiovascular deaths in older Australians., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Three-dimensional (3D) T1-weighted MRI sequences such as the magnetization prepared rapid gradient echo (MPRAGE) sequence are important for assessing regional cortical atrophy in the clinical evaluation of dementia but have long acquisition times and are prone to motion artifact. The recently developed Scout Accelerated Motion Estimation and Reduction (SAMER) retrospective motion correction method addresses motion artifact within clinically-acceptable computation times and has been validated through qualitative evaluation in inpatient and emergency settings., Methods: We evaluated the quantitative accuracy of morphometric analysis of SAMER motion-corrected compared to non-motion-corrected MPRAGE images by estimating cortical volume and thickness across neuroanatomical regions in two subject groups: (1) healthy volunteers and (2) patients undergoing evaluation for dementia. In part (1), we used a set of 108 MPRAGE reconstructed images derived from 12 healthy volunteers to systematically assess the effectiveness of SAMER in correcting varying degrees of motion corruption, ranging from mild to severe. In part (2), 29 patients who were scheduled for brain MRI with memory loss protocol and had motion corruption on their clinical MPRAGE scans were prospectively enrolled., Results: In part (1), SAMER resulted in effective correction of motion-induced cortical volume and thickness reductions. We observed systematic increases in the estimated cortical volume and thickness across all neuroanatomical regions and a relative reduction in percent error values compared to reference standard scans of up to 66 % for the cerebral white matter volume. In part (2), SAMER resulted in statistically significant volume increases across anatomical regions, with the most pronounced increases seen in the parietal and temporal lobes, and general reductions in percent error relative to reference standard clinical scans., Conclusion: SAMER improves the accuracy of morphometry through systematic increases and recovery of the estimated cortical volume and cortical thickness following motion correction, which may affect the evaluation of regional cortical atrophy in patients undergoing evaluation for dementia., Competing Interests: Declaration of competing interest Authors Wei-Ching Lo and Bryan Clifford are employees of Siemens Medical Solutions USA. Authors Daniel Polak and Daniel Nicolas Splitthoff are employees of Siemens Healthineers., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In this paper, we use the Health and Retirement Study (HRS) to examine the relationship between an estimated measure of pulse wave velocity (ePWV) and cognitive impairment with no dementia and dementia, respectively., Methods: We modeled the relationship between ePWV and cognitive status in 2006/2008 using data from 8,492 men and women (mean age 68.6 years) controlling for age, blood pressure, sociodemographic, and socioeconomic characteristics (sex, race and ethnicity, education, income, wealth), health behaviors (smoking and physical activity), body mass index (BMI), health status and related medication use (history of cardiovascular disease, diabetes, and stroke), and cerebrovascular disease (CVD)-related biomarkers (C-reactive protein, cystatin-C, hemoglobin A1c, total cholesterol, high-density lipoprotein [HDL] cholesterol). We assess cognitive function with the 27-item Langa-Weir Telephone Interview for Cognitive Status (TICS) scale. ePWV is derived from an equation based on participant age and resting blood pressure., Results: In a model that controlled for the constituent components of ePWV (age, age squared, systolic and diastolic blood pressure), ePWV is associated with increased odds of having cognitive impairment with no dementia (OR = 2.761) and dementia (OR = 6.344) relative to a group with no cognitive impairment or dementia. After controlling for the constituent components of ePWV, sociodemographic and socioeconomic characteristics, health behaviors, BMI, health status and medication use, and CVD-related biomarkers, ePWV remains significantly associated with dementia (OR = 3.969) but not cognitive impairment with no dementia (OR = 1.782)., Conclusions: These findings suggest that ePWV may be a novel research tool and biomarker of vascular aging that can be used in large, population-representative studies to examine cognitive aging and dementia risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Vision impairment is a potentially modifiable risk factor for dementia. Although few prior studies have estimated the contribution of vision impairments to dementia, none have reported on multiple objectively measured vision impairments (eg, distance and near visual acuity and contrast sensitivity) in a nationally representative sample of older adults., Objective: To quantify population attributable fractions of dementia from objective vision impairments in older adults, stratified by age, self-reported sex, self-reported race and ethnicity, and educational attainment., Design, Setting, and Participants: This was a population-based cross-sectional analysis in the National Health and Aging Trends Study, which gathers nationally representative information on Medicare beneficiaries aged 65 years and older in the US. A total of 2767 community-dwelling adults eligible for vision and cognitive testing in 2021 were included. Data were analyzed from April to August 2023., Exposures: Near and distance visual acuity impairments were each defined as >0.30 logMAR. Contrast sensitivity impairment was defined as <1.55 logCS. At least 1 vision impairment was defined as impairment to either near acuity, distance acuity, or contrast sensitivity., Main Outcomes and Measures: Adjusted population attributable fractions of prevalent dementia, defined using a standardized algorithmic diagnosis (≥1.5 SDs below mean on 1 or more cognitive domains, self- or proxy-reported dementia diagnosis, or the Ascertain Dementia-8 Dementia Screening Interview Score of probable dementia)., Results: The survey-weighted prevalence of vision impairment among participants aged 71 and older (1575 [54.7%] female and 1192 [45.3%] male; 570 [8.0%] non-Hispanic Black, 132 [81.7%] Hispanic, 2004 [81.7%] non-Hispanic White, and 61 [3.3%] non-Hispanic other) was 32.2% (95% CI, 29.7-34.6). The population attributable fraction of prevalent dementia from at least 1 vision impairment was 19.0% (95% CI, 8.2-29.7). Contrast sensitivity impairment yielded the strongest attributable fraction among all impairments (15.0%; 95% CI, 6.6-23.6), followed by near acuity (9.7%; 95% CI, 2.6-17.0) and distance acuity (4.9%; 95% CI, 0.1-9.9). Population attributable fractions from at least 1 impairment were highest among participants aged 71 to 79 years (24.3%; 95% CI, 6.6-41.8), female (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White (22.3%; 95% CI, 9.6-34.5) subpopulations, with estimates consistent across educational strata., Conclusions and Relevance: The population attributable fraction of dementia from vision impairments ranged from 4.9%-19.0%. While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia.

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose of the Review: In this review, we attempt to summarize the most updated studies that applied resting-state functional magnetic resonance imaging (rs-fMRI) in the field of Parkinsonisms and related dementia., Recent Findings: Over the past decades, increasing interest has emerged on investigating the presence and pathophysiology of cognitive symptoms in Parkinsonisms and their possible role as predictive biomarkers of neurodegenerative brain processes. In recent years, evidence has been provided, applying mainly three methodological approaches (i.e. seed-based, network-based and graph-analysis) on rs-fMRI data, with promising results. Neural correlates of cognitive impairment and dementia have been detected in patients with Parkinsonisms along the diseases course. Interestingly, early functional connectivity signatures were proposed to track and predict future progression of neurodegenerative processes. However, longitudinal studies are still sparce and further investigations are needed to overcome this knowledge gap., (© 2024. The Author(s).)

Falls, wheelchair dependence, and bedridden status are the results of reduced mobility in the mid-late course of dementia. Kinematic gait analysis for patients with dementia is lacking because practically setting sensors on their bodies is particularly difficult. We analyzed the parameters of kinematic gait analysis that are related to the risks of wheelchair dependence in patients with dementia using wearable accelerometers and gyroscopes for detecting 3-dimensional physical movements. We collected data from 34 patients with dementia regarding demographics, cognitive function, CT scan findings, medications, and gait analysis parameters. The patients were followed up for 6 months. We compared data between dementia patients with and without wheelchair dependence by t-test or Fisher's exact test, multiple comparison, and simple logistic regression analysis for wheelchair dependence by gait analysis parameters. Eleven patients became wheelchair-dependent during the 6 months. The score on the clinical dementia rating scale was significantly higher and the hip extensor angle in walking was significantly lower in patients with dementia with wheelchair dependence than in those without. The severity of dementia and the lower angle of the hip extensor during walking may indicate the necessity of a wheelchair for patients with this disease.

Purpose: To evaluate the impact of baseline and change in vision on the risk of developing dementia., Design: Retrospective cohort study., Methods: This longitudinal analysis utilized data from the 2021 and 2022 National Health and Aging Trends Study. Binocular presenting vision was assessed, including distance (DVA) and near (NVA) visual acuity, and contrast sensitivity (CS). Dementia status was defined based on: (1) medical diagnosis of dementia, (2) dementia score, or (3) poor cognitive test performance., Results: Of the 2,159 adults included in this study, weighted mean (SD) age was 77.9 years (5.2), with the majority being female (weighted: 54%), and White (88%). The baseline median (interquartile range [IQR]) DVA was 0.08 (0-0.20) logMAR, NVA was 0.17 (0.09-0.26) logMAR, and CS was 1.80 (1.65-1.85) logCS. Over the 1-year follow up period, 192 (6.6%) adults developed dementia. In time-to-event analyses, baseline DVA (HR: 1.08 [95% CI: 1.02-1.14], per 0.1 logMAR), NVA (HR: 1.07 [95% CI: 1.01-1.13], per 0.1 logMAR), and CS (HR: 1.09 [95% CI: 1.03-1.15], per 0.1 logCS) were associated with greater likelihood of incident dementia. Further, change in CS (HR: 1.14 [95% CI: 1.04-1.25], per 0.1 logCS worse/year), but not VA, was associated with greater likelihood of incident dementia., Conclusions: Worse baseline VA and CS are associated with greater likelihood of incident dementia. Further, worsening CS over time, but not VA, was associated with higher likelihood of incident dementia. Future work is needed to study interventions targeted at improving vision deficits and examine their impact on decreasing dementia risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent studies on machine learning have shown the potential to provide new methods with which to assess pain through the measurement of signals associated with physiologic responses to pain detected by wearables. We conducted a prospective pilot study to evaluate the real-world feasibility of using an AI-enabled wearable system for pain assessment with elderly patients with dementia and impaired communication., Methods: Sensor data were collected from the wearables, as well as observational data-based conventional everyday interventions. We measured the adherence, completeness, and quality of the collected data. Thereafter, we evaluated the most appropriate classification model for assessing the detectability and predictability of pain., Results: A total of 18 patients completed the trial period, and 10 of them had complete sensor and observational datasets. We extracted 206 matched records containing a 180 min long data segment from the sensor's dataset. The final dataset comprised 153 subsets labelled as moderate pain and 53 labelled as severe pain. After noise reduction, we compared the recall and precision performances of 14 common classification algorithms. The light gradient-boosting machine (LGBM) classifier presented optimal values for both performances., Conclusions: Our findings tended to show that electrodermal activity (EDA), skin temperature, and mobility data are the most appropriate for pain detection.

Background: The mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes., Aims: To evaluate the role of cortisol (as marker of the HPA, hypothalamus-pituitary-adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes., Methods: The AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL)., Results: The MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function. The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference)., Discussion: The AGICO study showed that the stress response is activated in the patients with depression., Conclusion: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome., (© 2024. The Author(s).)

This study aimed to clarify associations of clinical and neuropsychological features and change in regional cerebral blood flow (rCBF) on 123 I-IMP-SPECT in patients with Parkinson's disease (PD) who developed dementia. Sixty-one PD patients (mean age, 65.9 ± 8.6 years; mean disease duration, 11.0 ± 11.0 years) were recruited and followed-up for two years. Clinical and neuropsychological characteristics, and rCBF from SPECT were compared between PD patients who developed dementia (PDD+) and those who remained undemented (PDD-). Thirty-eight PD patients (62.3%) were diagnosed with PD-MCI at baseline. During follow-up, 22 PD patients (36%) developed dementia (PDD+). Univariate logistic regression models showed that Hoehn and Yahr scale 4 (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.35-30.75]), visual hallucination (OR 5.95; 95%CI 1.67-25.4]), and PD-MCI (OR 6.47; 95%CI 1.57-39.63]) represented a significant risk factor for PDD+. Among neuropsychological parameters, WAIS (Wechsler Adult Intelligence Scale)-III block design (OR 6.55; 95%CI 1.66-29.84), letter number sequencing (OR 7.01; 95%CI 1.65-36.64), digit-symbol coding (OR 3.90; 95%CI 1.13-14.2), Wechsler Memory Scale, revised (WMS-R) visual paired associates II (delayed recall) (OR 4.68; 95%CI 1.36-17.36), Logical memory I (immediate recall) (OR 8.30; 95%CI 1.37-90.89), Logical memory II (delayed recall) (OR 6.61; 95%CI 1.35-44.33), Visual reproduction I (immediate recall) (OR 7.67; 95%CI 2.11-31.40), and Visual reproduction II (delayed recall) (OR 5.64; 95%CI 1.62-21.47) were significant risk factors. Decreased rCBF assessed using the general linear model (two-sample t-test) by SPM8 was observed in the left precuneus (0, -66, 16), right cuneus (6, -76, 30), and left angular gyrus (-46, -74, 32) in PDD+ compared with PDD- patients. Collectively, we have here shown that clinical and neuropsychological characteristics as well as changes to rCBF in PD patients who converted to PDD+. These features should be carefully monitored to detect the development of dementia in PD patients.

This study aimed to compare the diagnostic performance of visual assessment of electroencephalography (EEG) using the Grand Total EEG (GTE) score and quantitative EEG (QEEG) using spectral analysis in the context of cognitive impairment. This was a retrospective study of patients with mild cognitive impairment, with (MCI+V) or without (MCI) vascular dysfunction, and patients with dementia including Alzheimer's disease, Lewy Body Dementia and vascular dementia. The results showed that the GTE is a simple scoring system with some potential applications, but limited ability to distinguish between dementia subtypes, while spectral analysis appeared to be a powerful tool, but its clinical development requires the use of artificial intelligence tools., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cognitive decline is a natural consequence of aging, but several genetic, environmental, and psychological factors can influence its trajectories. Among the most enduring factors, the Big Five personality traits - defined as relatively stable tendencies to think, behave, and react to the environment - can influence both directly (e.g., by physiological correlates) and indirectly (e.g., healthy or risky behaviors) the risk of developing dementia and mild cognitive impairment (MCI) - a preclinical form of cognitive decline. Despite the great amount of studies focusing on the relationship between personality and cognitive decline, an updated systematic synthesis of the results including a broader range of study designs is still lacking. This systematic review aims to summarize the findings of studies investigating: (i) differences in personality traits between groups of healthy individuals and those with MCI, (ii) the impact of personality traits on the risk for both MCI and dementia, and (iii) changes in personality traits among individuals progressing from normal cognition to MCI. Neuroticism emerged as a significant risk factor for MCI and dementia; Conscientiousness and Openness appear to offer protection against dementia and moderate cognitive decline. Overall, these findings suggest a pivotal role of personality structure in shaping cognitive outcomes on the long run., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Dementia is caused by neurodegenerative conditions and characterized by cognitive decline. Diagnostic accuracy for dementia subtypes, such as Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease with dementia (PDD), remains challenging., Methods: Here, different methods of quantitative electroencephalography (qEEG) analyses were employed to assess their effectiveness in distinguishing dementia subtypes from healthy controls under eyes closed (EC) and eyes open (EO) conditions., Results: Classic Fast-Fourier Transform (FFT) and autoregressive (AR) power analyses differentiated between all conditions for the 4-8 Hz theta range. Only individuals with dementia with Lewy Bodies (DLB) differed from healthy subjects for the wider 4-15 Hz frequency range, encompassing the actual dominant frequency of all individuals. FFT results for this range yielded wider significant discriminators vs AR, also detecting differences between AD and DLB. Analyses of the inclusive dominant / peak frequency range (4-15 Hz) indicated slowing and reduced variability, also discriminating between synucleinopathies vs controls and AD. Dissociation of periodic oscillations and aperiodic components of AR spectra using Fitting-Oscillations-&-One-Over-F (FOOOF) modelling delivered a reliable and subtype-specific slowing of brain oscillatory peaks during EC and EO for all groups. Distinct and robust differences were particularly strong for aperiodic parameters, suggesting their potential diagnostic power in detecting specific changes resulting from age and cognitive status., Conclusion: Our findings indicate that qEEG methods can reliably detect dementia subtypes. Spectral analyses comprising an integrated, multi-parameter EEG approach discriminating between periodic and aperiodic components under EC and EO conditions may enhance diagnostic accuracy in the future., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

With increases in life expectancy and the size of the aging population, cognitive decline and neurodegenerative pathologies are expected to increase in the next few decades. Age-related increases in risk for dementia and cardiovascular disease have been researched widely. Epidemiology trends reveal a predicted increase of neurodegenerative disease to more than 65 million by 2030 in the United States. There are several risk factors for the development of cardiovascular disease that have been widely studied for their impact on dementia; such as: diabetes, hypertension, and hyperlipidemia. Several pathophysiologic mechanisms exist by which cardiovascular disease could impact dementia including cerebral hypoperfusion, reactive oxidative species, and increased cleavage of amyloid precursor protein into amyloid beta plaques and accumulation of neurofibrillary tangles. Emerging evidence also suggests that treatment of cardiovascular disease risk factors could reduce the risk of dementia development. In this review, we seek to examine the relationship between cardiovascular disease and dementia by examining epidemiologic trends, common risk factors, pathophysiologic mechanisms and implications for clinical management., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Emerging and advanced technologies in the field of Artificial Intelligence (AI) represent promising methods to predict and diagnose neurodegenerative diseases, such as dementia. By using multimodal approaches, Machine Learning (ML) seems to provide a better understanding of the pathological mechanisms underlying the onset of dementia. The purpose of this review was to discuss the current ML application in the field of neuropsychology and electrophysiology, exploring its results in both prediction and diagnosis for different forms of dementia, such as Alzheimer's disease (AD), Vascular Dementia (VaD), Dementia with Lewy bodies (DLB), and Frontotemporal Dementia (FTD)., Methods: Main ML-based papers focusing on neuropsychological assessments and electroencephalogram (EEG) studies were analyzed for each type of dementia., Results: An accuracy ranging between 70 % and 90 % or even more was observed in all neurophysiological and electrophysiological results trained by ML. Among all forms of dementia, the most significant findings were observed for AD. Relevant results were mostly related to diagnosis rather than prediction, because of the lack of longitudinal studies with appropriate follow-up duration. However, it remains unclear which ML algorithm performs better in diagnosing or predicting dementia., Conclusions: Neuropsychological and electrophysiological measurements, together with ML analysis, may be considered as reliable instruments for early detection of dementia., Competing Interests: Declaration of Competing Interest All Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neurological disorders arise primarily from the dysfunction of brain cells, leading to various impairments. Electroencephalography (EEG) stands out as the most popular method in the discovery of neuromarkers indicating neurological disorders. The proposed study investigates the effectiveness of spectral and synchrony neuromarkers derived from resting state EEG in the detection of Mild Cognitive Impairment (MCI) with controls., New Methods: The dataset is composed of 10 MCI and 10 HC groups. Spectral features and synchrony measures are utilized to detect slowing patterns in MCI. Efficient neuro-markers are classified by 25 classification algorithm. Independent samples t-test and Pearson's Correlation Coefficients are applied to reveal group differences for spectral markers, and repeated measures ANOVA is tested for wPLI-based markers., Results: Lower peak amplitudes are prominent in MCI participants for high frequencies indicating slower physiological behavior of the demented EEG. The MCI and HC groups are correctly classified with 95 % acc. using peak amplitudes of beta band with LGBM classifier. Higher wPLI values are calculated for HC participants in high frequencies. The alpha wPLI values achieve a classification accuracy of 99 % using the LGBM algorithm for MCI detection., Comparison With Existing Methods: The neuro-markers including peak amplitudes, frequencies, and wPLIs with advanced machine learning techniques showcases the innovative nature of this research., Conclusion: The findings suggest that peak amplitudes and wPLI in high frequency bands derived from resting state EEG are effective neuromarkers for detection of MCI. Spectral and synchrony neuro-markers hold great promise for accurate MCI detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Markerless motion capture (MMC) uses video cameras or depth sensors for full body tracking and presents a promising approach for objectively and unobtrusively monitoring functional performance within community settings, to aid clinical decision-making in neurodegenerative diseases such as dementia., Objective: The primary objective of this systematic review was to investigate the application of MMC using full-body tracking, to quantify functional performance in people with dementia, mild cognitive impairment, and Parkinson disease., Methods: A systematic search of the Embase, MEDLINE, CINAHL, and Scopus databases was conducted between November 2022 and February 2023, which yielded a total of 1595 results. The inclusion criteria were MMC and full-body tracking. A total of 157 studies were included for full-text screening, out of which 26 eligible studies that met the selection criteria were included in the review. ., Results: Primarily, the selected studies focused on gait analysis (n=24), while other functional tasks, such as sit to stand (n=5) and stepping in place (n=1), were also explored. However, activities of daily living were not evaluated in any of the included studies. MMC models varied across the studies, encompassing depth cameras (n=18) versus standard video cameras (n=5) or mobile phone cameras (n=2) with postprocessing using deep learning models. However, only 6 studies conducted rigorous comparisons with established gold-standard motion capture models., Conclusions: Despite its potential as an effective tool for analyzing movement and posture in individuals with dementia, mild cognitive impairment, and Parkinson disease, further research is required to establish the clinical usefulness of MMC in quantifying mobility and functional performance in the real world., (©Julian Jeyasingh-Jacob, Mark Crook-Rumsey, Harshvi Shah, Theresita Joseph, Subati Abulikemu, Sarah Daniels, David J Sharp, Shlomi Haar. Originally published in JMIR Aging (https://aging.jmir.org), 06.08.2024.)

Background: We investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms., Methods: A population-based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n = 462) had 6-year follow-up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease., Results: In fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR] = 1.89; 95% confidence interval [CI] = 1.23-2.92) and CIND (HR = 1.55; 95% CI = 1.01-2.38) and CIND progression to dementia, although not statistically significantly (HR = 2.44; 95% CI = 0.78-6.88). People with poor PEF also experienced the fastest ventricular enlargement (β coefficient = 0.67 mL/year; 95% CI = 0.13-1.21) and had the highest likelihood of developing lacunes (odds ratio = 5.05; 95% CI = 1.01-25.23)., Discussion: Poor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage., Highlights: Poor lung function increased the risk of dementia and mild cognitive impairment (MCI). Poor lung function accelerated the progression from MCI to dementia. Poor lung function was linked to brain microvascular damage and global brain atrophy., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Although brain glymphatic dysfunction is a contributing factor to the cognitive deficits in Parkinson's disease (PD), its role in the longitudinal progression of cognitive dysfunction remains unknown., Objective: To investigate the glymphatic function in PD with mild cognitive impairment (MCI) that progresses to dementia (PDD) and to determine its predictive value in identifying individuals at high risk for developing dementia., Methods: We included 64 patients with PD meeting criteria for MCI and categorized them as either progressed to PDD (converters) (n = 29) or did not progress to PDD (nonconverters) (n = 35), depending on whether they developed dementia during follow-up. Meanwhile, 35 age- and gender-matched healthy controls (HC) were included. Bilateral diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) indices and enlarged perivascular spaces (EPVS) volume fraction in bilateral centrum semiovale, basal ganglia (BG), and midbrain were compared among the three groups. Correlations among the DTI-ALPS index and EPVS, as well as cognitive performance were analyzed. Additionally, we investigated the mediation effect of EPVS on DTI-ALPS and cognitive function., Results: PDD converters had lower cognitive composites scores in the executive domains than did nonconverters (P < 0.001). Besides, PDD converters had a significantly lower DTI-ALPS index in the left hemisphere (P < 0.001) and a larger volume fraction of BG-PVS (P = 0.03) compared to HC and PDD nonconverters. Lower DTI-ALPS index and increased BG-PVS volume fraction were associated with worse performance in the global cognitive performance and executive function. However, there was no significant mediating effect. Receiver operating characteristic analysis revealed that the DTI-ALPS could effectively identify PDD converters with an area under the curve (AUC) of 0.850., Conclusion: The reduction of glymphatic activity, measured by the DTI-ALPS, could potentially be used as a non-invasive indicator in forecasting high risk of dementia conversion before the onset of dementia in PD patients., (© 2024. The Author(s).)

Vascular pathologies are among the most common contributors to neurodegenerative changes across the spectrum of normal aging to dementia. Cerebral small vessel disease (SVD) encompasses a wide range of conditions affecting capillaries, small arteries, and arterioles, as well as perivascular spaces and fluid dynamics in the brain, playing a significant role in vascular contributions to cognitive impairment and dementia (VCID). These factors can accelerate the progression of SVD and neuronal degeneration. Since aging is the primary risk factor for Alzheimer's disease (AD) and AD-related dementias (ADRD), this Research Topic aims to gather recent research to better understand vascular contributions to healthy aging and age-related cognitive impairment. Other risk factors include diabetes, lifestyle factors, high cholesterol, vascular inflammation, and immune remodeling, all of which can accelerate cognitive dysfunction progression. This special issue includes a total of 21 articles comprising Reviews, Perspectives, and Original Research articles. The articles cover various technical and biological aspects related to recent progress in aging and dementia research. We aim to promote research exchange across different fields, including imaging, VCID, molecular biology, neuroinflammation, and immunology. Most papers in this special issue focus on understanding the disease mechanisms of AD/ADRD and developing new therapeutic strategies.

Background: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk., Methods: In this prospective cohort study, we used data from the population-based Trøndelag Health (HUNT) Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP, and estimated cardiorespiratory fitness across 3 surveys (HUNT1, 1984-1986 to HUNT3, 2006-2008). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-2019. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia., Results: In total, 7 594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1 062 (14.0%) participants. We identified 2 multidimensional trajectories throughout adulthood within 3 age groups: one with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, apolipoprotein E ε4 status, education, marital status, and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% confidence intervals [95% CI]: 0.51, 0.78) with corresponding RD of -0.07 (95% CI: -0.10, -0.04)., Conclusions: Having a beneficial multidimensional trajectory of SBP, DBP, and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP, and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: To examine relationships between visual function (ie, contrast sensitivity, visual field, color vision, and motion perception) and cognitive impairment, including any definition of "cognitive impairment," mild cognitive impairment, or dementia., Design: Systematic review and meta-analyses., Setting and Participants: Any settings; participants with (cases) or without (controls) cognitive impairment., Methods: We searched 4 databases (to January 2024) and included published studies that compared visual function between cases and controls. Standardized mean differences (SMD) with 95% CIs were calculated where data were available. Data were sufficient for meta-analyses when cases were people with dementia. The Joanna Briggs Institute checklists were used for quality assessment., Results: Fifty-one studies/69 reports were included. Cross-sectional evidence shows that people with dementia had worse contrast sensitivity function and color vision than controls: measured by contrast sensitivity (log units) on letter charts, SMD -1.22 (95% CI -1.98, -0.47), or at varied spatial frequencies, -0.92 (-1.28, -0.57); and by pseudoisochromatic plates, -1.04 (-1.59, -0.49); color arrangement, -1.30 (-2.31, -0.29); or matching tests, -0.51 (-0.78, -0.24). They also performed more poorly on tests of motion perception, -1.20 (-1.73, -0.67), and visual field: mean deviation, -0.87 (-1.29, -0.46), and pattern standard deviation, -0.69 (-1.24, -0.15). Results were similar when cases were limited to participants with clinically diagnosed Alzheimer disease. Sources of bias included lack of clarity on study populations or settings and definitions of cognitive impairment. The 2 included longitudinal studies with follow-ups of approximately 10 years were of good quality but reported inconsistent results., Conclusions and Implications: In the lack of longitudinal data, cross-sectional studies indicate that individuals with cognitive impairment have poorer visual function than those with normal cognition. Additional longitudinal data are needed to understand whether poor visual function precedes cognitive impairment and the most relevant aspects of visual function, dementia pathologies, and domains of cognition., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is composed by highly specialized microvessels, surrounded by astrocytes, pericytes, neurons and microglia cells, which tightly control the influx and efflux of substances to the brain parenchyma. During aging, the BBB becomes impaired, and it may contribute to the development of neurodegenerative and neurological disorders including Alzheimer's disease and other dementias. Restoring the BBB can be a strategy to prevent disease onset and development, reducing the symptoms of these conditions. This work critically reviews the major mechanisms underlying BBB breakdown in healthy and unhealthy aging, as well as biomarkers and methodologies that accurately assess its impairment. Complementarily, potential therapeutic targets are discussed as new strategies to restore the normal function of the BBB in aging., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To quantify health fluctuations, identify affected health-related quality of life (HRQoL) dimensions, and evaluate if fluctuations affect the HRQoL instruments recall period adherence in people living with dementia (PlwD)., Methods: Caregivers of PlwD completed a daily diary for 14 days, documenting if PlwD's health was better or worse than the day before and the affected HRQoL dimensions. Health fluctuation was categorized into low (0-4 fluctuations in 14 days), moderate (5-8), and high (9-14). Also, caregivers and PlwD completed the EQ-5D-5L (proxy- and self-reported) on days 1, 7, and 14. Subsequently, caregivers were interviewed to determine whether recurrent fluctuations were considered in the EQ-5D-5L assessment of today's health (recall period adherence)., Results: Fluctuations were reported for 96% of PlwD, on average, for 7 of the 14 days. Dimensions most frequently triggering fluctuations included memory, mobility, concentration, sleep, pain, and usual activities. Fluctuations were associated with higher EQ-5D-5L health-states variation and nonadherence to the EQ-5D-5L recall period "today." PlwD with moderate to high fluctuation had the highest EQ-5D-5L utility change between day 1 and 14 (0.157 and 0.134) and recall period nonadherence (31% and 26%) compared with PlwD with low fluctuation (0.010; 17%). Recall period nonadherence was higher in PlwD with improved compared with those with deteriorated health in the diary (37% vs 9%)., Conclusions: Health fluctuations frequently occur in dementia and strongly affect HRQoL assessments. Further research is needed to evaluate if more extended recall periods and multiple, consecutive assessments could capture health fluctuations more appropriately in dementia., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Subjective cognitive decline (SCD) is considered an early indicator of Alzheimer's disease. Previous evidence suggests that postmenopausal females are at heightened risk for developing dementia. However, the potential effects of gender (i.e. postmenopausal female) on functional connectivity density (FCD) in individuals with SCD are not well understood. A total of 56 healthy controls and 57 subjects with SCD were included. The short-range and long-range FCD (srFCD and lrFCD) mapping of each participant was calculated. The interactive effect of gender × diagnosis on the FCD was explored by two-way analysis of variance. The interaction effect of gender × diagnosis on lrFCD was primarily in the right middle frontal gyrus (MFG). The older males with SCD exhibited significantly enhanced lrFCD in the right MFG relative to other subgroups. The lrFCD of the right MFG was positively associated with cognitive performance in older females with SCD. Cognition-related functional terms were significantly related to the right MFG. Decreased lrFCD of the right MFG in cognitively normal older women may explain why postmenopausal females have a higher risk for progression to dementia than men. Furthermore, this altered pattern could be applied to identify individuals with a high risk for dementia., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Examination of the variability of stress biomarkers among people living with dementia and their family caregivers can provide evidence of stress reactions and corresponding self-regulation capacities, but no such research has been conducted to date. The aim of this study was to examine day-to-day variability patterns of salivary biomarkers in dyads of people living with dementia and their family caregivers and to investigate differences in variability patterns between music intervention and control groups. This study involved secondary analysis of data collected during a two-group, non-randomized open trial examining the effects of an 8-week music intervention on physiological stress markers. A total of 5791 salivary samples from 34 dyads were used to analyze the variability of morning and evening cortisol and of morning dehydroepiandrosterone sulfate (DHEA-S). The variability indices employed were the intra- and inter-individual standard deviation, coefficient of variation, and intra-class correlation coefficient. We found that family caregivers in the music intervention group had significantly greater coefficients of variation for all three biomarker endpoints than those in the control group. Our findings provide evidence that stress biomarkers in family caregivers with functional self-regulation capacities may be more likely to respond to music intervention. However, stress biomarkers in people living with dementia may not be responsive to music intervention, possibly due to their dysfunctional self-regulation capacities. Future stress biomarker studies involving dyads of people living with dementia and family caregivers should consider biomarker variability patterns in determining the effectiveness of behavioral interventions., Competing Interests: Author's noteAzita Emami currently affiliated with Yale School of Nursing, Yale University, CT, USA. Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Knowledge of how circadian rhythm influences brain health remains limited. We aimed to investigate the associations of accelerometer-measured circadian rest-activity rhythm (CRAR) with incident dementia, cognitive dysfunction, and structural brain abnormalities in the general population and underlying biological mechanisms., Methods: Fifty-seven thousand five hundred and two participants aged over 60 years with accelerometer data were included to investigate the association of CRAR with incidental dementia. Non-parametric CRAR parameters were utilized, including activity level during active periods of the day (M10), activity level during rest periods of the day (L5), and the relative difference between the M10 and L5 (relative amplitude, RA). Associations of CRAR with cognitive dysfunction and brain structure were studied in a subset of participants. Neuroimaging-transcriptomics analysis was utilized to identify the underlying molecular mechanisms., Results: Over 6.86 (4.94-8.78) years of follow-up, 494 participants developed dementia. The risk of incident dementia was associated with decreasing M10 (hazard ratio [HR] 1.45; 95% conference interval [CI], 1.28-1.64) and RA (HR 1.37; 95% CI, 1.28-1.64), increasing L5 (HR 1.14, 95% CI 1.07-1.21) and advanced L5 onset time (HR 1.12; 95% CI, 1.02-1.23). The detrimental associations were exacerbated by APOE ε4 status and age (>65 years). Decreased RA was associated with lower processing speed (Beta -0.04; SE 0.011), predominantly mediated by abnormalities in subcortical regions and white matter microstructure. The genes underlying CRAR-related brain regional structure variation were enriched for synaptic function., Conclusions: Our study underscores the potential of intervention targeting at maintaining a healthy CRAR pattern to prevent dementia risk., (© 2024 The Authors Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Objective: We investigated how well a visual associative learning task discriminates Alzheimer's disease (AD) dementia from other types of dementia and how it relates to AD pathology., Methods: 3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT's discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status ( n = 2,769, 77%)., Results: Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70-0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets., Conclusions: Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Importance: Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia., Objective: To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes., Design, Setting, and Participants: Using data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited., Main Outcomes and Measures: A multivariate sparse canonical correlation analysis was conducted to identify functional connectivity-informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined., Results: Among 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS-associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = -0.29; P < .001), agitation (R = -0.28; P = .001), and apathy (R = -0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P < .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: β = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI., Conclusions and Relevance: These findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.

Background: Gait variability is a common feature in neurodegenerative diseases and has been linked to cognitive impairment. Despite this link, the influence of specific cognitive domains, such as memory, visual spatial skills, executive function, and verbal function on gait variability is not well-understood., Objective: To investigate the predictive value of these specific cognitive domains on gait variability in people with mild cognitive impairment (MCI) and dementia during preferred and dual task walking., Method: One hundred and two participants with either MCI or dementia underwent a comprehensive cognitive assessment and completed preferred and dual-task walking trials on a pressure-sensing walkway. Gait variability was assessed using the PKMAS software. Lower extremity function was evaluated with a self-reported validated scale., Results: Our findings indicate that only visual spatial abilities had a moderate predictive value on gait variability [F (1, 78) = 17.30, p < 0.01, r = 0.43], both in preferred pace walking (70% direct effect) and dual-task walking (90% direct effect) (p's < 0.05). Additionally, lower extremity functional skills had a significant indirect effect (30%) on gait variability in preferred walking contexts., Conclusion: For individuals diagnosed with MCI or dementia, increased gait variability may be driven by deficits in visual spatial processing. An increased understanding of the role of visual spatial processing in gait variability can aid in the assessment and management of individuals with MCI or dementia, potentially leading to targeted interventions to improve mobility and safety., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health., Methods: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regressions were used to test the relationship between mitochondrial biology and well-being., Results: Spare respiratory capacity ( b = 12.76, confidence interval [CI] = 5.23-20.28, p = .001), maximum respiratory capacity ( b = 8.45, CI = 4.54-12.35, p < .0001), and ATP-linked respiration ( b = 10.11, CI = 5.05-15.18, p = .0001) were positively associated with physical functioning. At average ( b = -2.23, CI = -3.64 to -0.82, p = .002) and below average ( b = -4.96, CI = -7.22 to 2.70, p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect ( p = .65)., Conclusions: Findings suggest that higher mitochondrial respiratory capacity is associated with better psychological and physical health-a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being., (Copyright © 2024 by the American Psychosomatic Society.)

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio ® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (β = 0.30, 95% CI: 0.16-0.44) and executive function scores (β = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

Objective: To review the literature on the neurobiological mechanisms of obsessive-compulsive symptoms (OCS) in people with dementia., Data Sources: MEDLINE/PubMed, CENTRAL, and PsycNet databases were searched from inception to March 2023., Study Selection: Original studies of any methodology with newly published data on the neurobiological underpinnings of OCS in patients with dementia, regardless of patient age or comorbidity and publication year, were included. The following search terms were used: (Obses* OR compul* OR OCD) AND (cognitive de* OR cognitive dysfunction OR cognitive disfunction OR dementia)., Data Extraction: Individual study data were extracted onto a piloted extractions sheet., Results: Patients with dementia and OCS were reported to have atrophy and hypoperfusion of frontal, temporal, striatal, and limbic structures. Serotonergic agents may be efficacious in reducing OCS. One randomized controlled trial of paroxetine in behavioral symptoms of dementia did not show efficacy. Evidence of dopaminergic dysfunction is too sparse to draw conclusions. Microglia dysfunction mediates obsessive-compulsive-like symptoms. Mutations of microtubule-associated protein τ may increase the risk of OCS. Cognitive self-consciousness and obsessive-compulsive-related cognitions may mediate OCS in old age. Dysfunction of the processing of one class of stimuli may increase the salience of other classes of stimuli, leading to OCS., Conclusions: Frontal lobe hypometabolism and temporal lobe atrophy and hypometabolism are unexpected given previous research in obsessive compulsive disorder. Serotonergic agents have encouraging efficacy in case reports but require more specific research., Prim Care Companion CNS Disord 2024;26(3):23r03689 ., Author affiliations are listed at the end of this article., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background: Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension)., Methods: This study was a post hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed Using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy., Results: 8,563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002)., Conclusions: EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Dementia, and in particular Alzheimer's disease (AD), can be characterized by disrupted functional connectivity in the brain caused by beta-amyloid deposition in neural links. Non-pharmaceutical treatments for dementia have recently explored interventions involving the stimulation of neuronal populations in the gamma band. These interventions aim to restore brain network functionality by synchronizing rhythmic energy through various stimulation modalities. Entrainment, a newly proposed non-invasive sensory stimulation method, has shown promise in improving cognitive functions in dementia patients. This study investigates the effectiveness of entrainment in terms of promoting neural synchrony and spatial connectivity across the cortex. EEG signals were recorded during a 40 Hz auditory entrainment session conducted with a group of elderly participants with dementia. Phase locking value (PLV) between different intraregional and interregional sites was examined as an attribute of network synchronization, and connectivity of local and distant links were compared during the stimulation and rest trials. Our findings demonstrate enhanced neural synchrony between the frontal and parietal regions, which are key components of the brain's default mode network (DMN). The DMN operation is known to be impacted by dementia's progression, leading to reduced functional connectivity across the parieto-frontal pathways. Notably, entrainment alone significantly improves synchrony between these DMN components, suggesting its potential for restoring functional connectivity., (© 2024. The Author(s).)

Background: Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing)., Objective: Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period., Methods: Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF., Results: We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-β) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF., Conclusions: By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits., International Registered Report Identifier (irrid): DERR1-10.2196/56726., (©Pierfilippo De Sanctis, Jeannette R Mahoney, Johanna Wagner, Helena M Blumen, Wenzhu Mowrey, Emmeline Ayers, Claudia Schneider, Natasha Orellana, Sophie Molholm, Joe Verghese. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.06.2024.)

Purpose of the Report: Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD., Materials and Methods: In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years). Patients with PD were classified into 2 groups: the PD with dementia (PDD)-high-risk (PDD-H; n = 47) and the PDD-low-risk (PDD-L; n = 140) groups according to dementia conversion within 5 years of PD diagnosis. We explored between-group differences in the regional uptake in the early-phase 18 F-FP-CIT PET images. We additionally performed a linear discriminant analysis to develop a prediction model for early PDD conversion., Results: The PDD-H group exhibited hypoperfusion in Alzheimer's disease (AD)-prone regions (inferomedial temporal and posterior cingulate cortices, and insula) compared with the PDD-L group. A prediction model using regional uptake in the right entorhinal cortex, left amygdala, and left isthmus cingulate cortex could optimally distinguish the PDD-H group from the PDD-L group., Conclusions: Regional hypoperfusion in the AD-prone regions on early-phase 18 F-FP-CIT PET can be a useful biomarker for predicting early dementia conversion in patients with PD., Competing Interests: Conflicts of interest and sources of funding: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI23C0092)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD., Methods: In this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNR LC )., Results: The ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNR LC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNR LC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNR LC and the MoCA score in PD subjects., Conclusion: The ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD., Competing Interests: Declarations of competing interest All authors of this manuscript declare no conflicts of interest. Peng Wu reports a relationship with Philips Healthcare that includes: employment., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer's dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the role of neurovascular coupling in AD related dementia and its early stages. We included 25 subjective cognitive impairment, 33 mild cognitive impairment and 17 dementia patients and 44 controls. All participants underwent magnetic resonance imaging of the brain and neuropsychological assessment. Univariate general linear modeling analyses were used to assess neurovascular coupling between patient groups and controls. Moreover, linear regression analyses was used to assess the associations between neurovascular coupling and cognition. Our data show that BOLD amplitude is lower in dementia (mean 0.8 ± 0.2, p = 0.001) and MCI patients (mean 0.9 ± 0.3, p = 0.004) compared with controls (mean 1.1 ± 0.2). A low BOLD amplitude was associated with low scores in multiple cognitive domains. We conclude that cerebrovascular dysfunction, most likely due CAA, is an important comorbidity in early stages of dementia and has an independent effect on cognition., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms significantly impact sleep, emotional, and cognitive functions, with its synchronization depending on light exposure. We performed a meta-analysis to evaluate the effects of light therapy on sleep, depression, neuropsychiatric behaviors, and cognition among PLWD., Methods: A systematic search was conducted in Cochrane, ClinicalTrials.gov, Embase, EBSCOhost, Ovid-MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The pooled effect size was calculated using the Hedges' g with random-effects model adopted in comprehensive meta-analysis software. The Cochrane risk of bias (RoB 2.0) tool evaluated the quality of studies, while Cochrane's Q and I² tests assessed heterogeneity., Results: A total of 24 studies with 1,074 participants were included. Light therapy demonstrated small-to-medium effects on improving sleep parameters: total sleep time (Hedges' g = 0.19), wake after sleep onset (Hedges' g = 0.24), sleep efficiency (Hedges' g = 0.31), sleep latency (Hedges' g = 0.35), circadian rhythm (acrophase: Hedges' g = 0.36; amplitude: Hedges' g = 0.43), number of night awakenings (Hedges' g = 0.37), sleep disturbance (Hedges'g = 0.45), and sleep quality (Hedges' g = 0.60). Light therapy showed small-to-medium effect on reducing depression (Hedges' g = -0.46) with medium-to-large effect on cyclical function (Hedges' g = -0.68) and mood-related signs and symptoms (Hedges' g = -0.84) subscales. Light therapy also demonstrated small effect on reducing neuropsychiatric behaviors (Hedges' g = -0.34) with medium-to-large effect on agitation (Hedges' g = -0.65), affective symptom (Hedges' g = -0.70), psychosis (Hedges' g = -0.72), and melancholic behavior (Hedges' g = -0.91) subscales. Additionally, light therapy also improved cognition (Hedges' g = 0.39)., Conclusion: Light therapy could be used as a supportive therapy to improve sleep, depression, cognition, and neuropsychiatric behaviors among PLWD., Competing Interests: DISCLOSURES The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, or publication of this article., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)