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Objectives: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. Methods: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. Results: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. Conclusions: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases. [ABSTRACT FROM AUTHOR]

Whole body vibration (WBV) is linked to short- and longer-term adverse health outcomes, including cognitive impairment, stress and memory loss, loss of balance, reduced proprioception, visual and vestibular disturbances, gastrointestinal problems, and musculoskeletal disorders. Epidemiological evidence supports the link between WBV and headache and head discomfort, but few experimental studies have examined this relationship, particularly with increased muscle tension, as an intermediary. This study aimed to investigate the relationship between muscle tension and vibration intensity, between perceived neck pain and headache/head discomfort and vibration intensity, and between muscle tension and reported neck pain and headache symptoms from simulated WBV based on field measurements of all-terrain vehicle operation on farm terrain. We observed significantly higher electromyography amplitude in the High condition (equivalent to EU Directive's Exposure Limit Value) compared to both Low (equivalent to EU Directive's Exposure Action Value) and Control (quiet sitting) conditions at the left upper trapezius muscle but there were no significant time effects. Neck pain and headache/head discomfort significantly increased after both Low (91% increase from baseline) and High (154% increase from baseline) vibration conditions but there were no significant differences between conditions. Based on simple regression modeling, the relationship between muscle activity and neck pain or headache was very weak (R 2 = 0–0.093). Given the possibility of multiple factors contributing to headache symptoms, future research should not only consider the role of muscle tension but also sensory conflict, excessive noise, biodynamic responses, and a combination of these factors. [ABSTRACT FROM AUTHOR]

Positive effects of new anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer's disease (AD) have been attributed to brain amyloid reduction. However, most anti-Aβ antibodies also increase the CSF levels of the 42-amino acid isoform (Aβ42). We evaluated the associations of changes in CSF Aβ42 and brain Aβ-PET with cognitive and clinical end points in randomized trials of anti-Aβ drugs that lowered (β- and γ-secretase inhibitors) or increased CSF Aβ42 levels (anti-Aβ monoclonal antibodies) to test the hypothesis that post-treatment increases in CSF Aβ42 levels are independently associated with cognitive and clinical outcomes. From long-term (≥12 months) randomized placebo-controlled clinical trials of anti-Aβ drugs published until November 2023, we calculated the post-treatment versus baseline difference in ADAS-Cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) and CDR-SB (Clinical Dementia Rate-Sum of Boxes) and z -standardized changes in CSF Aβ42 and Aβ-PET Centiloids (CL). We estimated the effect size [regression coefficients (RCs) and confidence intervals (CIs)] and the heterogeneity (I2) of the associations between AD biomarkers and cognitive and clinical end points using random-effects meta-regression models. We included 25 966 subjects with AD from 24 trials. In random-effects analysis, increases in CSF Aβ42 were associated with slower decline in ADAS-Cog (RC: −0.55; 95% CI: −0.89, −0.21, P = 0.003, I2 = 61.4%) and CDR-SB (RC: −0.16; 95% CI: −0.26, −0.06, P = 0.002, I2 = 34.5%). Similarly, decreases in Aβ–PET were associated with slower decline in ADAS-Cog (RC: 0.69; 95% CI: 0.48, 0.89, P < 0.001, I2 = 0%) and CDR-SB (RC: 0.26; 95% CI: 0.18, 0.33, P < 0.001, I2 = 0%). Sensitivity analyses yielded similar results. Higher CSF Aβ42 levels after exposure to anti-Aβ drugs are independently associated with slowing cognitive impairment and clinical decline. Increases in Aβ42 may represent a mechanism of potential benefit of anti-Aβ monoclonal antibodies in AD. [ABSTRACT FROM AUTHOR]

During role-differentiated bimanual movements (RDBM), an object is typically stabilized with 1 hand and manipulated with the other. RDBM require coupling both hands for coordinated action (achieved through interhemispheric connections), but also inhibition of crosstalk to avoid involuntary movements in the stabilizing hand. We investigated how healthy cognitive aging and mild cognitive impairments (MCI) affect force stabilization during an RDBM in a cohort sequential study design with up to 4 measurement points over 32 months. In total, 132 older adults (>80 years) participated in this study, 77 were cognitively healthy individuals (CHI) and 55 presented with MCI. Participants performed a visuomotor bimanual force-tracking task. They either produced a constant force with both hands (bimanual constant) or a constant force with 1 and an alternating force with the other hand (role-differentiated). We investigated force fluctuations of constant force production using the coefficient of variation (CV), detrended fluctuation analysis (DFA), and sample entropy (SEn). Results showed higher CV and less complex variability structure (higher DFA and lower SEn) during the role-differentiated compared to the bimanual constant task. Furthermore, CHI displayed a more complex variability structure during the bimanual constant, but a less complex structure during the role-differentiated task than MCI. Interestingly, this complexity reduction was more pronounced in CHI than MCI individuals, suggesting different changes in the control mechanisms. Although understanding these changes requires further research, potential causes might be structural deteriorations leading to less efficient (intra- and interhemispheric) networks because of MCI, or an inability to appropriately divert the focus of attention. [ABSTRACT FROM AUTHOR]

Objectives This study examined the extent to which multiple relationship-specific attachment schemas (general, parent-child, and romantic) are interrelated and relate to depressive symptoms among older adults living with early-stage dementia and their adult children, a context likely to activate the attachment system. Methods The study consisted of 150 early-stage cognitively impaired parents and one child. Both self-reported general, parent-child, and romantic attachment anxiety as well as avoidance and depressive symptoms. Parents' cognitive and functional impairment were assessed. Results Most attachment variables were interrelated for individuals, except that the child's parent-child-specific avoidance was not associated with their general or romantic avoidance. The parent's worse functional, but not cognitive, impairment was associated with the child's greater parent-child-specific attachment anxiety. Using Actor Partner Interdependence Models, general attachment anxiety was associated with greater depressive symptoms (actor effects). When both dyad members were high in general avoidance, depressive symptoms were greatest (actor × partner effect). A parent had the greatest depressive symptoms when they were avoidantly attached to their child (role × actor effect) and their child was high in anxiety and low in avoidance toward them (role × partner effects). A child had the greatest depressive symptoms when they were low in avoidance toward the parent (role × actor effect) and the parent was low in anxiety and high in avoidance toward the child (role × partner effects). Romantic anxiety was associated with greater depressive symptoms (actor effects). Discussion Psychosocial interventions that incorporate attachment theory as a framework may benefit parent-child dyads coping with dementia. [ABSTRACT FROM AUTHOR]

Background Despite high long-term survival rates, pediatric low-grade gliomas (pLGGs) are linked with significant tumor- and treatment-associated morbidities that may persist throughout life. The aims of this descriptive cross-sectional pilot study were to characterize health conditions among a cohort of patients with pLGG and explore the feasibility of quantifying disease burden and healthcare resource utilization (HRU). Methods Optum® Market Clarity Data were used to identify patients aged ≤18 years with an ICD-10 code for brain neoplasm, ≥1 physician notes, and with evidence of pLGG recorded between January 1, 2017 and June 30, 2018. Outcomes including health characteristics, HRU, medications, and procedures were assessed at 6-month intervals over 36 months. Results One hundred and fifty-four patients were identified with pLGG and over half experienced headache/migraine, respiratory infection, pain, or behavioral issues during the 36-month study period. The most common comorbidities were ocular/visual (including blindness), mental health disorders, seizures, and behavioral/cognition disorders. Most symptoms and comorbidities persisted or increased during the study period, indicating long-term health deficits. HRU, including speciality care visits, filled prescriptions, and administered medications, was common; 74% of patients had prescriptions for anti-infectives, 56% antiemetics, and 52% required pain or fever relief. Sixty-five percent of patients underwent treatment to control their pLGG, the most common being brain surgery. Little decline was observed in medication use during the study period. Conclusions Patients with pLGG have complex healthcare needs requiring high HRU, often over a long time. Patients need to be optimally managed to minimize disease- and treatment-related burden and HRU. [ABSTRACT FROM AUTHOR]

Context Histidine-containing dipeptides (carnosine, anserine, beta-alanine and others) are found in human muscle tissue and other organs like the brain. Data in rodents and humans indicate that administration of exogenous carnosine improved cognitive performance. However, RCTs results vary. Objectives To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of histidine-containing dipeptide (HCD) supplementation on cognitive performance in humans to assess its utility as a cognitive stabiliser. Data Sources OVID Medline, Medline, EBM Reviews, Embase, and Cumulative Index to Nursing and Allied Health Literature databases from 1/1/1965 to 1/6/2022 for all RCT of HCDs were searched. Data Extraction 2653 abstracts were screened, identifying 94 full-text articles which were assessed for eligibility. Ten articles reporting the use of HCD supplementation were meta-analysed. Data Analysis The random effects model has been applied using the DerSimonian-Laird method. HCD treatment significantly increased performance on Wechsler Memory Scale (WMS) −2 Delayed recall (Weighted mean difference (WMD) (95% CI (CI)) = 1.5 (0.6, 2.5), P < .01). Treatment with HCDs had no effect on Alzheimer's Disease Assessment Scale-Cognitive (WMD (95% CI) = −0.2 (−1.1, 0.7), P = .65, I2 = 0%), Mini-Mental State Examination (WMD (95% CI) = 0.7 (−0.2, 1.5), P = .14, I2 = 42%), The Wechsler Adult Intelligence Scale (WAIS) Digit span Backward (WMD (95% CI) = 0.1 (−0.3, 0.5), P = .51, I2 = 0%), WAIS digit span Forward (WMD (95% CI) = 0.0 (−0.3, 0.4), P = .85, I2 = 33%) and the WMS-1 Immediate recall (WMD (95% CI) = .7 (−.2, 1.5), P = .11, I2 = 0%). The effect on delayed recall remained in subgroup meta-analysis performed on studies of patients without mild cognitive impairment (MCI), and in those without MCI where average age in the study was above 65. Conclusion HCD, supplementation improved scores on the Delayed recall examination, a neuropsychological test affected early in Alzheimer's disease. Further studies are needed in people with early cognitive impairment with longer follow-up duration and standardization of carnosine doses to delineate the true effect. Systematic Review Registration PROSPERO registration no. CRD42017075354. [ABSTRACT FROM AUTHOR]

Gantenerumab, a human monoclonal antibody (mAb), has been thought of as a potential agent to treat Alzheimer's disease (AD) by specifically targeting regions of the amyloid-β (Aβ) peptide sequence. Aβ protein accumulation in the brain leads to amyloid plaques, causing neuroinflammation, oxidative stress, neuronal damage, and neurotransmitter dysfunction, thereby causing cognitive decline in AD. Gantenerumab involves disrupting Aβ aggregation and promoting the breakdown of larger Aβ aggregates into smaller fragments, which facilitates the action of Aβ-degrading enzymes in the brain, thus slowing down the progression of AD. Moreover, Gantenerumab acts as an opsonin, coating Aβ plaques and enhancing their recognition by immune cells, which, combined with its ability to improve the activity of microglia, makes it an intriguing candidate for promoting Aβ plaque clearance. Indeed, the multifaceted effects of Gantenerumab, including Aβ disaggregation, enhanced immune recognition, and improved microglia activity, may position it as a promising therapeutic approach for AD. Of note, reports suggest that Gantenerumab, albeit its capacity to reduce or eliminate Aβ, has not demonstrated effectiveness in reducing cognitive decline. This review, after providing an overview of immunotherapy approaches that target Aβ in AD, explores the efficacy of Gantenerumab in reducing Aβ levels and cognitive decline. [ABSTRACT FROM AUTHOR]

Background We aimed to analyse the differences in the risk of geriatric syndromes between older adults with and without coronavirus disease 2019 (COVID-19). Methods We conducted a retrospective cohort study of patients from the US Collaborative Network in the TriNetX between January 1, 2020, and December 31, 2022. We included individuals aged older than 65 years with at least 2 health care visits who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests during the study period. We excluded those with SARS-CoV-2 vaccination, diagnosis with neoplasm and geriatric syndromes before the index date, and death within 30 days after the index date. The index date was defined as the first date of the PCR test for SARS-CoV-2 during the study period. Hazard ratios (HRs) and 95% confidence intervals (CIs) for eight geriatric syndromes were estimated for propensity score-matched older adults with and without COVID-19. Subgroup analyses of sex and age were also performed. Results After propensity score matching, 315 826 patients were included (mean [standard deviation] age, 73.5 [6.4] years; 46.7% males and 51.7% females). The three greatest relative increases in the risk of geriatric syndromes in the COVID-19 cohort were cognitive impairment (HR: 3.13; 95% CI: 2.96–3.31), depressive disorder (HR: 2.72; 95% CI: 2.62–2.82) and pressure injury (HR: 2.52; 95% CI: 2.34–2.71). Conclusions The risk of developing geriatric syndromes is much higher in the COVID-19 cohort. It is imperative that clinicians endeavour to prevent or minimise the development of these syndromes in the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

Design An observational cohort study conducted at a tertiary referral center for aortic surgery to describe the medical and surgical characteristics of patients assessed for abdominal aortic aneurysm repair and examine associations with 12-month outcome. Methods Patients with aortic aneurysms referred for discussion at the aortic multidisciplinary meeting (MDM). Data were collected via a prospectively maintained clinical database and included aneurysm characteristics, patient demographics, co-morbidities, geriatric syndromes, including frailty, management decision and 12-month mortality, both aneurysm-related and all-cause including cause of death. The operative and non-operative groups were compared statistically. Results 621 patients referred to aortic MDM; 292 patients listed for operative management, 141 patients continued on surveillance, 138 patients for non-operative management. There was a higher 12-month mortality rate in the non-operative group compared to the operative group (41% vs 7%, P = <0.001). In the non-operative group, 16 patients (29%) died of aneurysm rupture within 12 months, with 39 patients (71%) dying from other medical causes. Non-operatively managed patients were older, more likely to have cardiac and respiratory disease and more likely to be living with frailty, cognitive impairment and functional limitation, compared to the operative group. Conclusion This study shows that preoperative geriatric syndromes and increased comorbidity lead to shared decision to non-operatively manage asymptomatic aortic aneurysms. Twelve-month mortality is higher in the non-operative group with the majority of deaths occurring due to cause other than aneurysm rupture. These findings support the need for preoperative comprehensive geriatric assessment followed by multispecialty discussion and shared decision making. [ABSTRACT FROM AUTHOR]

In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults. [ABSTRACT FROM AUTHOR]

Objective Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer's disease (AD; i.e. Aβ + older adults), and pre-symptomatic autosomal dominant Alzheimer's disease (ADAD). In ADAD, Met66 was also associated with greater increases in CSF levels of total-tau (t-tau) and phosphorylated tau (p-tau181). This study sought to determine the extent to which BDNF Val66Met is associated with changes in episodic memory and CSF t-tau and p-tau181 in Aβ + older adults in early-stage sporadic AD. Method Aβ + Met66 carriers (n  = 94) and Val66 homozygotes (n  = 192) enrolled in the Alzheimer's Disease Neuroimaging Initiative who did not meet criteria for AD dementia, and with at least one follow-up neuropsychological and CSF assessment, were included. A series of linear mixed models were conducted to investigate changes in each outcome over an average of 2.8 years, covarying for CSF Aβ42, APOE ε4 status, sex, age, baseline diagnosis, and years of education. Results Aβ + Met66 carriers demonstrated significantly faster memory decline (d  = 0.33) and significantly greater increases in CSF t-tau (d  = 0.30) and p-tau181 (d  = 0.29) compared to Val66 homozygotes, despite showing equivalent changes in CSF Aβ42. Conclusions These findings suggest that reduced neurotrophic support, which is associated with Met66 carriage, may increase vulnerability to Aβ-related tau hyperphosphorylation, neuronal dysfunction, and cognitive decline even prior to the emergence of dementia. Additionally, these findings highlight the need for neuropsychological and clinicopathological models of AD to account for neurotrophic factors and the genes which moderate their expression. [ABSTRACT FROM AUTHOR]

Objective to establish a proof-of-concept and ascertain the reliability of an abbreviated 30-second (30s) phonemic fluency measure as a cognitive screening tool in older adults. Methods in all, 201 English-speaking individuals with normal cognition (NC; n  = 119) or cognitive impairment (CI; mild CI or dementia; n  = 82) were administered a standard 60s phonemic fluency task (FAS/CFL) with discrete 30s intervals denoted. Results for all letters, 30s trial scores significantly predicted 60s scores for the same letter, R 2 = .7–.9, F (1, 200) = 850–915, p  < .001. As with 60s total scores, 30s cumulative scores (for all three trials) were significantly different between NC and CI groups (p  < .001). Receiver operating characteristic analyses showed that 30s total scores distinguished NC and CI groups as effectively (AUC = .675) as 60s total scores (AUC = .658). Conclusions these findings support the utility and reliability of a short-form phonemic fluency paradigm, as 30s performance reliably predicted 60s/trial totals and was equally accurate in distinguishing impaired/non-impaired groups. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system's function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms. Study Design A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x -, y -, and z -axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables. Study Results People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F  = 9.001, P  = .011; F  = 10.024, P  = .011; F  = 5.927, P  = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia. Conclusion Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Abnormal thalamic nuclei volumes and their link to cognitive impairments have been observed in schizophrenia. However, whether and how this finding extends to the schizophrenia spectrum is unknown. We hypothesized a distinct pattern of aberrant thalamic nuclei volume across the spectrum and examined its potential associations with cognitive symptoms. Study Design We performed a FreeSurfer-based volumetry of T1-weighted brain MRIs from 137 healthy controls, 66 at-risk mental state (ARMS) subjects, 89 first-episode psychosis (FEP) individuals, and 126 patients with schizophrenia to estimate thalamic nuclei volumes of six nuclei groups (anterior, lateral, ventral, intralaminar, medial, and pulvinar). We used linear regression models, controlling for sex, age, and estimated total intracranial volume, both to compare thalamic nuclei volumes across groups and to investigate their associations with positive, negative, and cognitive symptoms. Study Results We observed significant volume alterations in medial and lateral thalamic nuclei. Medial nuclei displayed consistently reduced volumes across the spectrum compared to controls, while lower lateral nuclei volumes were only observed in schizophrenia. Whereas positive and negative symptoms were not associated with reduced nuclei volumes across all groups, higher cognitive scores were linked to lower volumes of medial nuclei in ARMS. In FEP, cognition was not linked to nuclei volumes. In schizophrenia, lower cognitive performance was associated with lower medial volumes. Conclusions Results demonstrate distinct thalamic nuclei volume reductions across the schizophrenia spectrum, with lower medial nuclei volumes linked to cognitive deficits in ARMS and schizophrenia. Data suggest a distinctive trajectory of thalamic nuclei abnormalities along the course of schizophrenia. [ABSTRACT FROM AUTHOR]

In our previous paper on the Future of Cognitive Remediation published more than 10 years ago, we envisaged an imminent and wide implementation of cognitive remediation therapies into mental health services. This optimism was misplaced. Despite evidence of the benefits, costs, and savings of this intervention, access is still sparse. The therapy has made its way into some treatment guidance, but these documents weight the same evidence very differently, causing confusion, and do not consider barriers to implementation. This paper revisits our previous agenda and describes how some challenges were overcome but some remain. The scientific community, with its commitment to Open Science, has produced promising sets of empirical data to explore the mechanisms of treatment action. This same community needs to understand the specific and nonspecific effects of cognitive remediation if we are to provide a formulation-based approach that can be widely implemented. In the last 10 years we have learned that cognitive remediation is not "brain training" but is a holistic therapy that involves an active therapist providing motivation support, and who helps to mitigate the impact of cognitive difficulties through metacognition to develop awareness of cognitive approaches to problems. We conclude that, of course, more research is needed but, in addition and perhaps more importantly at this stage, we need more public and health professionals' understanding of the benefits of this therapy to inform and include this approach as part of treatment regimens. [ABSTRACT FROM AUTHOR]

Background The increasing incidence of brain metastases (BMs) and improved survival rates underscore the necessity to investigate the effects of treatments on individuals. The aim of this study was to evaluate the individual trajectories of subjective and objective cognitive performance after radiotherapy in patients with BMs. Methods The study population consisted of adult patients with BMs referred for radiotherapy. A semi-structured interview and comprehensive neurocognitive assessment (NCA) were used to assess both subjective and objective cognitive performance before, 3 months and ≥ 11 months after radiotherapy. Reliable change indices were used to identify individual, clinically meaningful changes. Results Thirty-six patients completed the 3-month follow-up, and 14 patients completed the ≥ 11-months follow-up. Depending on the domain, subjective cognitive decline was reported by 11–22% of patients. In total, 50% of patients reported subjective decline in at least one cognitive domain. Intracranial progression 3 months postradiotherapy was a risk-factor for self-reported deterioration (P  = .031). Objective changes were observed across all domains, with a particular vulnerability for decline in memory at 3 months postradiotherapy. The majority of patients (81%) experienced both a deterioration as well as improvement (eg, mixed response) in objective cognitive functioning. Results were similar for the long-term follow-up (3 to ≥11 months). No risk factors for objective cognitive change 3 months postradiotherapy were identified. Conclusions Our study revealed that the majority of patients with BMs will show a mixed cognitive response following radiotherapy, reflecting the complex impact. This underscores the importance of patient-tailored NCAs 3 months postradiotherapy to guide optimal rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer's disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice developing AD-like amyloidogenesis. Our findings revealed that the early upregulation of A2AR in the presence of an ongoing amyloid pathology exacerbates memory impairments of APP/PS1 mice. These behavioural changes were not linked to major change in the development of amyloid pathology but rather associated with increased phosphorylated tau at neuritic plaques. Moreover, proteomic and transcriptomic analyses coupled with quantitative immunofluorescence studies indicated that neuronal upregulation of the receptor promoted both neuronal and non-neuronal autonomous alterations, i.e. enhanced neuroinflammatory response but also loss of excitatory synapses and impaired neuronal mitochondrial function, presumably accounting for the detrimental effect on memory. Overall, our results provide compelling evidence that neuronal A2AR dysfunction, as seen in the brain of patients, contributes to amyloid-related pathogenesis and underscores the potential of A2AR as a relevant therapeutic target for mitigating cognitive impairments in this neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

Background The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments. Aim To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS. Methods Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed. Results Final regression models including different sets of predictions were statistically significant (P  < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints. Conclusion Depression symptoms seem to be associated with transcranial magnetic stimulation–indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS. Trial registration ClinicalTrials.gov ID NCT03371225. [ABSTRACT FROM AUTHOR]

Background Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. Methods Participants without overt thyroid dysfunction aged 35–74 years at baseline were evaluated in 3 study waves (2008–2010, 2012–2014, and 2017–2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z -score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. Results In 9 524 participants (mean age 51.2 ± 8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (β = −0.004, 95% CI = −0.007; −0.001, p  = .014), verbal fluency (β = −0.003, 95% CI = −0.007; −0.0005, p  = .021), executive function (β = −0.004, 95% CI = −0.011; −0.003, p  < .001), and global cognition decline (β = −0.003, 95% CI = −0.006; −0.001, p  = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (β = −0.003, 95% CI = −0.007; −0.0004, p  = .025) and executive function (β = −0.004, 95% CI = −0.007; −0.0003, p  = .031) decline. Conclusions An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up. [ABSTRACT FROM AUTHOR]

Background Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. Methods To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. Results The cohort was followed up for an average of 5.25 (SE  = 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (p  = 8.63E-09, beta = 1.74, SE  = 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1 000 iterations. Conclusions These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance. [ABSTRACT FROM AUTHOR]

Background The association between change in lifestyle and cognitive impairment remains uncertain. Objectives To investigate the association of change in lifestyle with cognitive impairment. Methods In this study, 4 938 participants aged 65 or older were involved from the Chinese Longitudinal Healthy Longevity Survey for years 2008–2018. A weighted healthy lifestyle score was derived from 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet). Multivariable Cox proportional hazards regression models were applied to investigate the associations between 3-year changes in healthy lifestyle (2008–2011) and cognitive impairment (2011–2018). Results Researchers documented 833 new-onset of cognitive impairments more than 20 097 person-years of follow up. Compared with those in the persistently unhealthy group, those in the improved and persistently healthy groups had a lower risk of cognitive impairment, with the multivariate-adjusted hazard ratios (HRs) of 0.67 (95% confidence interval (CI): 0.55, 0.83) and 0.53 (95% CI: 0.40, 0.71), respectively. Furthermore, a significant interaction was observed between change in lifestyle and sex (p -interaction = .032); the HRs were 0.48 (95% CI, 0.34, 0.69) for the improved group and 0.41 (95% CI: 0.26, 0.64) for persistently healthy group among male vs 0.81 (95% CI, 0.63, 1.04) and 0.64 (95% CI, 0.44, 0.92) among female, respectively. Conclusions This study suggests that improving or maintaining a healthy lifestyle can significantly mitigate the risk of cognitive impairment in Chinese older adults. Additionally, researcher's findings emphasize the significance of maintaining a healthy lifestyle and highlights the potential positive impact of improving previous unhealthy habits, especially for older women. [ABSTRACT FROM AUTHOR]

Background Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. Methods Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. Results Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. Conclusions Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes. [ABSTRACT FROM AUTHOR]

Objectives Prior scholarship has highlighted the importance of marriage for cognition. However, little research has considered how cognition-related concerns may impact marriage. In this study, researchers examine how aging couples view each other's memory and worry about their potential development of dementia in the future. Additionally, researchers investigate whether these cognition-related concerns may strain marriage, and how these dynamics differ for men and women in same- and different-sex marriages. Methods Researchers used 2 waves of dyadic data from the Health and Relationships Project (HARP; 2015–2022), including 594 respondents from 297 same- and different-sex married couples (aged 41–71 at Time 2). Researchers employed the Actor–Partner Interdependence Model (APIM) to explore associations between actor and partner reports of memory and dementia worry with marital strain. Results Men and women in same- and different-sex marriages were equally likely to report worries about their own potential development of dementia. However, women reported more concerns about their spouse developing dementia in the future than men did, regardless of whether they were married to a man or a woman. Both partners' reports of memory and dementia worry played a complex role in influencing marital strain, with variations observed across couple types. Discussion Concerns about cognitive decline and dementia are common in older populations, and for married couples, spouses have concerns about their own memory as well as that of their partner. Researchers finding identified the significance of concerns about a spouse's memory on marital dynamics among aging couples. [ABSTRACT FROM AUTHOR]

Background and Objectives Amyloid positron emission tomography scans can enhance the accuracy of dementia diagnoses. However, the perspectives and experiences of people with cognitive impairment and their care partners undergoing an amyloid scan are less well understood. Therefore, this review aimed to identify and summarize qualitative studies exploring patient and care partner experiences of undergoing an amyloid scan. Research Design and Methods We searched Embase, MEDLINE, and PsychInfo in March 2024. Articles were screened for inclusion by 2 reviewers and critically appraised using the Joanna Briggs Institute Critical Appraisal Tool for Qualitative Studies. Data from the included studies were synthesized using thematic synthesis. Results We identified 10 papers from 6 studies. We identified 4 themes: (1) motivations for undergoing an amyloid scan, (2) experiences of receiving the result, (3) emotional responses to the result, and (4) actions in light of the scan result. Participants reported undergoing the scan to determine the cause of cognitive impairment. They described the information gained from the scan as helpful but struggled to recall the correct terminology or implications of the scan. Emotional responses to the scan varied depending on the scan result. In light of the scan result, the most common action was making advanced plans; however, this was mainly discussed among participants with elevated amyloid. Discussions and Implications Amyloid scans can provide useful and actionable information. However, learning the scan result could be distressing. Future research is needed to balance the potential benefits and harms of amyloid scans. [ABSTRACT FROM AUTHOR]

Background and Objectives Cognitive impairment and Alzheimer's disease and related dementias (ADRD) pose significant challenges for Indigenous populations, necessitating urgent research. Limited evidence suggests that high rates of ADRD among Indigenous peoples are associated with social determinants of health (SDOH), such as education, income, health literacy, religion, and social engagement. Research Design and Methods Collaborating with a Northern Plains tribe, participants were recruited 123 self-identified Indigenous women aged 40–70 through a comprehensive recruitment strategy. Employing the SDOH framework, the research assessed cognitive impairment and Alzheimer's disease knowledge (ADK), utilizing the Ascertain Dementia 8 and Alzheimer's disease knowledge scales (ADK-30). The investigation examined the relationships between selected SDOH variables and cognitive impairment status. Results More than half of the participants showed signs of cognitive impairment, which correlated with lower income and education levels. Increased knowledge about Alzheimer's disease, particularly in terms of treatment management and its life impact subscales, was associated with lower odds of cognitive impairment. Conversely, higher levels of depressive symptoms and participation in religious activities were linked to increased odds of cognitive impairment. Discussion and Implications The findings underscore the importance of culturally grounded tools and SDOH frameworks tailored to Indigenous contexts in addressing ADRD disparities. Future research should integrate historical and cultural factors to advance health equity within Indigenous communities, ultimately mitigating the impact of ADRD and promoting overall well-being. [ABSTRACT FROM AUTHOR]

Background and Objectives Little is known about how to prevent falls in community-dwelling older people with dementia. Although their care partners adopt various behaviors to prevent their falls, it is unclear if these behaviors reduce falls for those with different levels of fall risk. Research Design and Methods Linking the 2015 and 2016 National Health and Aging Trends Study and the 2015 National Study of Caregiving (NSOC), we identified 390 community-dwelling older people with dementia with 607 care partners. We selected 26 NSOC items representing fall risk management (FRM) behaviors. We examined the prevalence and dimensionality of these behaviors and investigated associations between care partners' behaviors in 2015 (T1) and older people's falls in 2016 (T2) stratified by their fall incidence at T1, adjusting for covariates. Results Five domains of FRM were identified: mobility and safety assistance, medical service coordination, health management, social service coordination, and accommodation. For those who did not fall at T1, mobility and safety assistance and social service coordination were each associated with an increased risk of falling at T2 (adjusted incidence rate ratio [aIRR] = 1.39, 95% confidence interval [CI] = 1.06–1.83, p =.019, aIRR = 1.25, 95% CI = 1.01–1.55, p =.043). For those who had fallen at T1, social service coordination was associated with a decreased risk of falling at T2 (aIRR = 0.83, 95% CI = 0.73–0.94, p =.004). Discussion and Implications The different impacts of dementia care partners' FRM behaviors emphasize the need to address specific behaviors when involving care partners in preventing falls for older people with dementia at varying levels of fall risk. [ABSTRACT FROM AUTHOR]

Objective There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. Methods From the multicentre retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. Results Two hundred patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (odds ratio [OR] 2.90; 95% CI: 1.25, 7.10; P  = 0.01) and more often presented with seizures (OR 8.31; 95% CI: 2.77, 33.04; P  < 0.001) or cognitive impairment (OR 2.58; 95% CI: 1.11, 6.10; P  = 0.03). On imaging, biopsy positive patients more often had non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80; 95% CI: 15.72, 233.06; P  < 0.001) or ≥1 cerebral microbleed (OR 8.08; 95% CI: 3.03, 25.13; P  < 0.001), and less often had ≥1 acute brain infarct (OR 0.02; 95% CI: 0.004, 0.08; P  < 0.001). In the multivariable model, non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (adjusted OR 8.27; 95% CI: 1.78, 38.46; P  < 0.01) and absence of ≥1 acute brain infarct (adjusted OR 0.13; 95% CI: 0.03, 0.65; P  = 0.01) were significantly associated with a positive biopsy. Conclusion Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS. [ABSTRACT FROM AUTHOR]

Background 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were useful for predicting large vessel disease, but the relationships between them and cerebral small vessel disease (CSVD) were unclear. Our study aimed to evaluate associations of 10-year ASCVD risk scores with CSVD and its magnetic resonance imaging (MRI) markers. Methods Community-dwelling residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included in this cross-sectional study. At baseline, we collected data related to the Framingham Risk Score (FRS), pooled cohort equation (PCE), prediction for ASCVD risk in China (China-PAR) and Systematic COronary Risk Evaluation model 2 (SCORE2), and classified participants into low, moderate and high groups. Participants underwent brain MRI scans. We evaluated white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS) according to criteria of Wardlaw and Rothwell, and calculated total CSVD score and modified total CSVD score. Results A total of 3063 participants were included, and 53.5% of them were female. A higher FRS was associated with higher total CSVD score (moderate vs. low: cOR 1.89, 95% CI 1.53–2.34; high vs. low: cOR 3.23, 95%CI 2.62–3.97), and the PCE, China-PAR or SCORE2 score was positively related to total CSVD score (P  < 0.05). Moreover, higher 10-year ASCVD scores were associated with higher odds of WMH (P  < 0.05), lacunes (P  < 0.05), CMBs (P  < 0.05) and BG-EPVS (P  < 0.05). Conclusions The 10-year ASCVD scores were positively associated with CSVD and its MRI markers. These scores provided a method of risk stratification in the population with CSVD. [ABSTRACT FROM AUTHOR]

Background Postoperative cognitive dysfunction (POCD) manifests as a subtle decline in cognition, potentially leading to unfavourable postoperative outcomes. We explored the impact of POCD on physical function, length of hospital stay (LOS), dementia and mortality outcomes. Methods PubMed and Scopus were searched until May 2023. All studies of major surgical patients that assessed POCD and outcomes of interest were included. POCD effects were stratified by surgery type (cardiac and noncardiac) and time of POCD assessment (<30 and ≥30 days postsurgery). Results Of 2316 studies, 20 met the inclusion criteria. POCD was not associated with functional decline postsurgery. Patients who experienced POCD postcardiac surgery had an increased relative risk (RR) of death of 2.04 [(95% CI: 1.18, 3.50); I 2 = 0.00%]. Sensitivity analyses showed associations with intermediate-term mortality among noncardiac surgical patients, with an RR of 1.84 [(95% CI: 1.26, 2.71); I 2 = 0.00%]. Patients who developed POCD <30 days postcardiac and noncardiac surgeries experienced longer LOS than those who did not [mean difference (MD) = 1.37 days (95% CI: 0.35, 2.39); I 2 = 92.38% and MD = 1.94 days (95% CI: 0.48, 3.40); I 2 = 83.29%, respectively]. Postoperative delirium (POD) may contribute to the heterogeneity observed, but limited data were reported within the studies included. Conclusions Patients undergoing cardiac and noncardiac surgeries who developed POCD <30 days postsurgery had poorer outcomes and an increased risk of premature death. Early recognition of perioperative neurocognitive disorders in at-risk patients may enable early intervention. However, POD may confound our findings, with further studies necessary to disentangle the effects of POD from POCD on clinical outcomes. [ABSTRACT FROM AUTHOR]

Globally, more people are living into advanced old age, with age-associated frailty, disability and multimorbidity. Achieving equity for all ages necessitates adapting healthcare systems. Clinical practice guidelines (CPGs) have an important place in adapting evidence-based medicine and clinical care to reflect these changing needs. CPGs can facilitate better and more systematic care for older people. But they can also present a challenge to patient-centred care and shared decision-making when clinical and/or socioeconomic heterogeneity or personal priorities are not reflected in recommendations or in their application. Indeed, evidence is often lacking to enable this variability to be reflected in guidance. Evidence is more likely to be lacking about some sections of the population. Many older adults are at the intersection of many factors associated with exclusion from traditional clinical evidence sources with higher incidence of multimorbidity and disability compounded by poorer healthcare access and ultimately worse outcomes. We describe these challenges and illustrate how they can adversely affect CPG scope, the evidence available and its summation, the content of CPG recommendations and their patient-centred implementation. In all of this, we take older adults as our focus, but much of what we say will be applicable to other marginalised groups. Then, using the established process of formulating a CPG as a framework, we consider how these challenges can be mitigated, with particular attention to applicability and implementation. We consider why CPG recommendations on the same clinical areas may be inconsistent and describe approaches to ensuring that CPGs remain up to date. [ABSTRACT FROM AUTHOR]

Background Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. Objective The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory–Self-Report (McSCI-S), are reported. Methods Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. Results A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P  < .001), controlling for age, sex and education. Conclusions Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs. [ABSTRACT FROM AUTHOR]

Background The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period. Methods Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants). Depressive symptoms were assessed at baseline and at yearly assessments during a follow-up period of up to 5 years, using the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests, including the Mini Mental State Exam, Stroop test, Letter Digit Coding test and immediate and delayed recall. A novel method, dynamic time warping analysis, was employed to model their temporal dynamics within individuals, in undirected and directed time-lag analyses, to ascertain whether depressive symptoms precede cognitive decline in group-level aggregated results or vice versa. Results The 325 participants were all 85 years of age at baseline; 68% were female, and 45% received intermediate to higher education. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the constituents of cognitive impairment in the oldest old. Of the GDS-15 symptoms, those with the strongest outstrength, indicating changes in these symptoms preceded subsequent changes in other symptoms, were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all P 's < 0.01). Conclusion Depressive symptoms preceded cognitive impairment in a population based sample of the oldest old. [ABSTRACT FROM AUTHOR]

Background We aimed to analyze the trajectories of cognitive decline as a function of the presence of type 2 diabetes and glycemic control in analyzes stratified by sex in an 8-year follow-up period. Methods A total of 1 752 men and 2 232 women aged ≥50 years who participated in the English Longitudinal Study of Ageing (ELSA), conducted from 2004 to 2012, were analyzed. The outcomes of interest were performance on the cognitive domains of memory, executive function, and temporal orientation as well as the global cognition score. Cognitive performance was standardized in z -scores in strata based on schooling and age. The participants were classified as without diabetes, with controlled glycemia, and with uncontrolled glycemia, according to medical diagnosis, glucose-lowering medications use and HbA1c levels. Generalized linear mixed models controlled by sociodemographic, behavioral, and health-related characteristics were used for the trajectory analyses. Results No differences in z -scores were found for global cognition or cognitive domains based on diabetes classification in men and women at baseline. More than 8 years of follow up, women with uncontrolled glycemia had a greater decline in z -scores for global cognition (−0.037 SD /year [95% CI: −0.073; −0.001]) and executive function (−0.049 SD /year [95% CI: −0.092; −0.007]) compared with those without diabetes. No significant difference in trajectories of global cognition or any cognitive domain was found in men as a function of diabetes classification. Conclusions Women with uncontrolled glycemia are at greater risk of a decline in global cognition and executive function than those without diabetes. [ABSTRACT FROM AUTHOR]

Background Cardiometabolic risk (CMR) is associated with cognitive health, but the association can be affected by broader social, economic, and medical contexts. The United States and China have very different developmental and epidemiological histories, and thus CMR among older people could be linked to cognitive function differently in the 2 countries. Methods Cross-sectional and longitudinal ordinary least squares regression models were estimated for each country using nationally representative samples of populations over age 50: 7 430/4 474 Americans and 6 108/3 655 Chinese in the cross-sectional/longitudinal samples. Results In the United States, higher CMR is associated with worse cognitive function (b  = −0.08, p  < .016). Longitudinally, CMR increase is associated with worse cognitive function at a marginally significant level (b  = −0.10, p  = .055). No relationship between CMR level or change and cognitive function is observed in China. Higher education levels are linked to better cognitive function and slower cognitive decline in both countries. Unlike older Americans, relative to those with very low education levels, among older Chinese with the highest education level, a higher CMR links to better cognitive function (b  = 0.63, p  = .013) and slower cognitive decline (b  = 0.35, p  = .062); Nevertheless, a rapid increase in CMR is additionally harmful (b  = −0.54, p  = .050) for cognitive function and may lead to faster cognitive decline (b  = −0.35, p  = .079). Conclusions The significant relationship between CMR and cognitive function in the United States suggests the importance of monitoring and controlling CMR factors at older ages. The insignificant relationship in China may be explained by the high CMR among those with high education levels, highlighting the need for improving cardiometabolic health through education and promoting healthy lifestyles. [ABSTRACT FROM AUTHOR]

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aβ deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated. [ABSTRACT FROM AUTHOR]

Background Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition. Methods A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n  = 33; 72.7% men) and healthy controls (n  = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated. Results Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample. Conclusions The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline. [ABSTRACT FROM AUTHOR]

Background and Hypothesis This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Study Results Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Conclusions Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood. Study Design We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g -computation formula. Study Results In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results. Conclusions Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Cognitive difficulties significantly burdened people with schizophrenia (PWS). However, cognitive assessment is often unavailable in low- and middle-income counties (LMICs) due to a lack of validated and culturally adapted cognitive assessment tools. In this study, we developed and evaluated a culturally sensitive cognitive battery for PWS in Ethiopia. Study Design This study was conducted in three phases. First, we selected appropriate tests through an instrument selection procedure and created a new battery. Then, we rigorously adapted the tests using culturally competent procedures, including cognitive interviewing and expert meetings. Finally, we tested the new battery in 208 PWS and 208 controls. We evaluated its psychometric properties using advanced statistical techniques, including Item Response Theory (IRT). Study Results The Ethiopian Cognitive Assessment battery for Schizophrenia (ECAS) was developed from three different batteries. Participants reported tests were easy to complete, and the raters found them easy to administer. All tests had good inter-rater reliability, and the composite score had very high test-retest reliability (ICC = 0.91). One-factor structure better represented the data with excellent internal consistency (α = .81). ECAS significantly differentiated PWS from controls with 77% sensitivity and 62% specificity at a Z -score ≤0.12 cut-off value. IRT analysis suggested that the battery functions best among moderately impaired participants (difficulty between −0.06 and 0.66). Conclusions ECAS is a practical, tolerable, reliable, and valid assessment of cognition. ECAS can supplement current assessment tools in LAMICs for PWS and can be used to measure cognitive intervention outcomes. [ABSTRACT FROM AUTHOR]

It has become consensus that mild cognitive impairment (MCI), one of the early symptoms onset of Alzheimer's disease (AD), may appear 10 or more years after the emergence of neuropathological abnormalities. Therefore, understanding the progression of AD biomarkers and uncovering when brain alterations begin in the preclinical stage, while patients are still cognitively normal, are crucial for effective early detection and therapeutic development. In this paper, we develop a Bayesian semiparametric framework that jointly models the longitudinal trajectory of the AD biomarker with a changepoint relative to the occurrence of symptoms onset, which is subject to left truncation and right censoring, in a heterogeneous population. Furthermore, unlike most existing methods assuming that everyone in the considered population will eventually develop the disease, our approach accounts for the possibility that some individuals may never experience MCI or AD, even after a long follow-up time. We evaluate the proposed model through simulation studies and demonstrate its clinical utility by examining an important AD biomarker, ptau181, using a dataset from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study. [ABSTRACT FROM AUTHOR]

Context Although several epidemiological studies have examined the association between coffee or tea intake and the risk of cognitive disorders, the results to date are inconsistent. Objective An updated systematic review and dose–response meta-analysis was conducted to confirm the association between coffee, tea, and caffeine consumption and the risk of cognitive disorders. Data Sources PubMed, Embase, and Web of Science were searched from inception to January 2022 for relevant studies, including dementia, Alzheimer disease (AD), and cognitive impairment or decline. Data Extraction Two reviewers independently performed data extraction and assessed the study quality. Data Analysis Restricted cubic splines were used to conduct the dose–response meta-analysis for coffee and tea intake. Results Twenty-two prospective studies and 11 case-control studies involving 389 505 participants were eligible for this meta-analysis. Coffee and tea consumption was linked to a lower risk of cognitive disorders, with an overall relative risk (RR) of 0.73 (95% CI: 0.60–0.86) and 0.68 (95% CI: 0.56–0.80), respectively. The subgroup analysis revealed that ethnicity, sex, and outcomes had significant effects on this association. Protection was stronger for men than that for women in both coffee and tea consumption. A nonlinear relationship was found between coffee consumption and AD risk, and the strength of protection peaked at approximately 2.5 cups/day (RR: 0.74; 95% CI: 0.59–0.93). A linear relationship was found between tea consumption and cognitive disorders, and the risk decreased by 11% for every 1-cup/day increment. Conclusion This meta-analysis demonstrated that the consumption of 2.5 cups coffee/day minimizes the risk of AD, and 1 cup/day of tea intake leads to an 11% reduction in cognitive deficits. Effective interventions involving coffee and tea intake might prevent the occurrence of dementia. [ABSTRACT FROM AUTHOR]

Objective This study aimed to determine the predictive values of informant-reported memory decline (IMD) among subjective cognitive decline (SCD) older adults from a 7-year community-based cohort study. Method Ninety SCD participants were included. Demographic data and neuropsychological test scores at both baseline and 7-year follow-up were collected. Differences between SCD with IMD (+IMD) and SCD without IMD (−IMD) were compared. Logistic regression models were used to determine whether baseline IMD could predict diagnostic outcomes at 7-year follow-up. Results Forty-one percent of SCD adults had IMD. At baseline, the +IMD group showed more depressive symptoms (p  = 0.016) than the −IMD group. Furthermore, the Beijing-version Montreal Cognitive Assessment (MoCA), Digit Span Test-Forward, Visual Matching and Reasoning, and Wechsler Adult Intelligence Scale-RC Picture Completion (WAIS-PC) scores in the +IMD group were significantly lower than those in the −IMD group. Fifty-four percent of +IMD participants converted to mild cognitive impairment (MCI) or dementia at follow-up, and 22.6% of the −IMD participants converted to MCI. Follow-up Mini-Mental State Examination, MoCA, and Verbal Fluency Test scores of the +IMD group were significantly lower than those in the −IMD group. The +IMD group was more likely to progress to cognitive impairment at 7-year follow-up (OR = 3.361, p  = 0.028). Conclusions SCD participants with +IMD may have poorer cognition and are more likely to convert to cognitive impairment over time. Our long-term follow-up study confirmed the importance of informants' perceptions of SCD, which can help clinicians identify individuals at risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Recent longitudinal PET imaging studies have established methods to estimate the age at which amyloid becomes abnormal at the level of the individual. Here we recontextualized amyloid levels into the temporal domain to better understand the downstream Alzheimer's disease processes of tau neurofibrillary tangle (NFT) accumulation and cognitive decline. This cohort study included a total of 601 individuals from the Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center that underwent amyloid and tau PET, longitudinal neuropsychological assessments and met clinical criteria for three clinical diagnosis groups: cognitively unimpaired (n = 537); mild cognitive impairment (n = 48); or dementia (n = 16). Cortical 11C-Pittsburgh compound B (PiB) distribution volume ratio (DVR) and sampled iterative local approximation were used to estimate amyloid positive (A+; global PiB DVR > 1.16 equivalent to 17.1 centiloids) onset age and years of A+ duration at tau PET (i.e. amyloid chronicity). Tau PET burden was quantified using 18F-MK-6240 standardized uptake value ratios (70–90 min, inferior cerebellar grey matter reference region). Whole-brain and region-specific approaches were used to examine tau PET binding along the amyloid timeline and across the Alzheimer's disease clinical continuum. Voxel-wise 18F-MK-6240 analyses revealed that with each decade of A+, the spatial extent of measurable tau spread (i.e. progressed) from regions associated with early to late NFT tau stages. Regional analyses indicated that tau burden in the entorhinal cortex was detectable, on average, within 10 years of A+ onset. Additionally, the entorhinal cortex was the region most sensitive to early amyloid pathology and clinical impairment in this predominantly preclinical sample. Among initially cognitively unimpaired (n = 472) individuals with longitudinal cognitive follow-up, mixed effects models showed significant linear and non-linear interactions of A+ duration and entorhinal tau on cognitive decline, suggesting a synergistic effect whereby greater A+ duration, together with a higher entorhinal tau burden, increases the likelihood of cognitive decline beyond their separable effects. Overall, the amyloid time framework enabled a spatiotemporal characterization of tau deposition patterns across the Alzheimer's disease continuum. This approach, which examined cross-sectional tau PET data along the amyloid timeline to make longitudinal disease course inferences, demonstrated that A+ duration explains a considerable amount of variability in the magnitude and topography of tau spread, which largely recapitulated NFT staging observed in human neuropathological studies. By anchoring disease progression to the onset of amyloid, this study provides a temporal disease context, which may help inform disease prognosis and timing windows for anti-amyloid therapies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is neurodegenerative and characterized by progressive cognitive impairment. Synaptic dysfunction appears in the early stage of Alzheimer's disease and is significantly correlated with cognitive impairment. However, the specific regulatory mechanism remains unclear. Here, we found the transcription factor Maf1 to be upregulated in Alzheimer's disease and determined that conditional knockout of Maf1 in a transgenic mouse model of Alzheimer's disease restored learning and memory function; the downregulation of Maf1 reduced the intraneuronal calcium concentration and restored neuronal synaptic morphology. We also demonstrated that Maf1 regulated the expression of NMDAR1 by binding to the promoter region of Grin1 , further regulating calcium homeostasis and synaptic remodelling in neurons. Our results clarify the important role and mechanism of the Maf1-NMDAR1 signalling pathway in stabilizing synaptic structure, neuronal function and behaviour during Alzheimer's disease pathogenesis. This therefore serves as a potential diagnostic and therapeutic target for the early stage of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams. [ABSTRACT FROM AUTHOR]

Objectives It is well known that low educational attainment is associated with cognitive function decline in older age. Childhood book availability may help to preserve cognitive function in older adults with low education. The study objective was to examine the association between childhood book availability and cognitive function among older adults with low educational attainment, and to investigate the mediating effect of the volume of reading-related brain regions (e.g. superior temporal cortex). Methods A cross-sectional study of community-dwelling older Japanese adults aged 65–84 years was conducted (n  = 474). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Childhood book availability was assessed using a retrospective questionnaire. Brain region volume was measured using magnetic resonance imaging. Multivariate regression modeling and structural equation modeling were used for analysis. Results Both high educational attainment and childhood book availability were independently associated with high MMSE score. Stratification of educational level showed that childhood book availability was positively associated with MMSE score among participants with low educational attainment (coefficient = 1.48, 95% confidence interval [CI]: 0.31 to 2.66), but not among those with moderate or high educational attainment (coefficient = −0.01, 95% CI: −1.44 to 1.42 and −1.21, 95% CI: −3.85 to 1.42, respectively). Among participants with low educational attainment, left superior temporal cortex volume mediated the association between childhood book availability and MMSE score. Discussion The availability of books in childhood helps to preserve cognitive function in older adults with low education via left superior temporal cortex volume. Further research is needed to replicate these findings. [ABSTRACT FROM AUTHOR]

Fictional stories set in care homes have increased in the last decades and, with them, the perspectives from which care homes are constructed and represented have become diversified. Care home stories. Aging, disability, and long-term residential care. Transcript Verlag]. Through the alternative worlds that are offered by literary narratives, these stories allow the reader to glimpse into the increasingly varied possibilities of care that a residential settlement can offer. At the same time, they highlight the attributes attached to human beings once their bodies are not regarded as fully functional or able by their carers and society at large. Jackie Kay's short story "These are not my clothes" (2011) presents a highly symbolic care-home narrative in which constant practices of depersonalized care and infantilization lead to the inevitable dehumanization of the residents and their eventual deterioration. Through the viewpoint of its female protagonist, Margaret, Kay creates a personal, poignant and, at times, also humorous narrative of care that undermines prevailing images of the so-called fourth age as a period of extreme cognitive deterioration. Drawing from theories of care and the interdisciplinary field of aging studies, especially in connection with theories of embodiment and old age and social approaches to aging, this article offers a close reading of Kay's short story as both an assertive narrative on the fourth age, and as an insubordinate story of care, which can serve as a model to both gerontologists and care practitioners. [ABSTRACT FROM AUTHOR]

Background and Objectives The primary aim of this Stage IB randomized controlled trial (RCT) was to test the preliminary effects of a dual-task exergaming telerehabilitation intervention on cognition and aerobic fitness, compared to aerobic exercise (AEx) only and attention control (stretching) in older adults with subjective cognitive decline. Research Design and Methods This RCT randomized 39 participants on a 2:1:1 allocation ratio to supervised exergame (n  = 20), AEx (n  = 11), and stretching (n  = 8) for 12 weeks. The dual-task exergaming was concurrent moderate-intensity cycling and BrainFitRx cognitive telerehabilitation. Cognition was assessed by NIH Toolbox Cognitive Battery and aerobic fitness by 6-minute walk test (6MWT) and shuttle walk test. Results The participants were 74.6 (7.4) years old and 69% were female. The effect of time was significant, F (1, 23.9) = 13.16, p  = .001, for the Fluid Composite score, and significant within-group changes were seen for the exergame group, t (14.08) = 2.53, p  = .024, d  = 0.33. Between-group changes did not reach significant levels for any cognitive test. Between-group changes for the 6MWT were not significant. Discussion and Implications The exergame participants further improved their fluid cognition, whereas the AEx and stretching groups did not, indicating a potential synergistic effect from AEx and cognitive training. The aerobic fitness changes were similar between the exergame and AEx-only groups, indicating that the feasibility of adding cognitive training to AEx concurrently without sacrificing gains in aerobic fitness from AEx. This study shows the flexibility of exergame delivery and its potentially therapeutic effects in persons at risk for Alzheimer's dementia. Clinical Trial Registration Number NCT04311736 [ABSTRACT FROM AUTHOR]