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A 78-year-old woman with hypertension, diabetes mellitus type 2 and bilateral sensorineural hearing loss was referenced to geriatric psychiatry consultation. She presented cognitive dysfunction, erotomanic delusion and complex musical hallucinations (MH), described as hearing her neighbour singing a familiar church song along with bells in the background, making comments and talking to her. A computed tomography (CT) of the brain detected small right nucleocapsular and bilateral external capsules hypodensities of presumed vascular aetiology during hospitalisation. MH are a rare phenomenon with heterogeneous aetiology. Most frequently, the cause is hearing impairment; other causes include social isolation, cognitive dysfunction, vascular risk factors and medication. Studies suggest that some brain areas related to musical memory circuitry might be related and not fully mapped. Auditory verbal hallucinations with a voice that either comments, talks or sings to the patient have never been described in the literature, making this clinical case attractive. info:eu-repo/semantics/publishedVersion

Objectives:To test the hypothesis that higher level of purpose in life is associated with lower likelihood of dementia and mild cognitive impairment (MCI) in older Brazilians.Methods:As part of the Pathology, Alzheimer’s and Related Dementias Study (PARDoS), informants of 1,514 older deceased Brazilians underwent a uniform structured interview. The informant interview included demographic data, the Clinical Dementia Rating scale to diagnose dementia and MCI, the National Institute of Mental Health Diagnostic Interview Schedule for depression, and a 6-item measure of purpose in life, a component of well-being.Results:Purpose scores ranged from 1.5 to 5.0 with higher values indicating higher levels of purpose. On the Clinical Dementia Rating Scale, 940 persons (62.1%) had no cognitive impairment, 121 (8.0%) had MCI, and 453 (29.9%) had dementia. In logistic regression models adjusted for age at death, sex, education, and race, higher purpose was associated with lower likelihood of MCI (odds ratio = .58; 95% confidence interval [CI]: .43, .79) and dementia (odds ratio = .49, 95% CI: .41, .59). Results were comparable after adjusting for depression (identified in 161 [10.6%]). Neither race nor education modified the association of purpose with cognitive diagnoses.Conclusions:Higher purpose in life is associated with lower likelihood of MCI and dementia in older black and white Brazilians.

OBJECTIVE: To determine if surgery and anesthesia in the elderly may promote Alzheimer’s Disease and Related Dementias (ADRD). BACKGROUND: There is a substantial conflicting literature concerning the hypothesis that surgery and anesthesia promotes ADRD. Much of the literature is confounded by indications for surgery or has small sample size. This study examines elderly patients with appendicitis, a common condition that strikes mostly at random after controlling for some known associations. METHODS: A matched natural experiment of patients undergoing appendectomy for appendicitis versus control patients without appendicitis using Medicare data from 2002 to 2017, examining 54,996 patients without previous diagnoses of ADRD, cognitive impairment, or neurological degeneration, who developed appendicitis between ages 68 through 77 years and underwent an appendectomy (the “Appendectomy” treated group), matching them 5:1 to 274,980 controls, examining the subsequent hazard for developing ADRD. RESULTS: The hazard ratio (HR) for developing ADRD or death was lower in the Appendectomy group than controls: HR = 0.96 (95% CI 0.94, 0.98), P < 0.0001, (28.2% in Appendectomy versus 29.1% in controls, at 7.5 years). The HR for death was 0.97 (0.95, 0.99), P = 0.002, (22.7% versus 23.1% at 7.5 years). The HR for developing ADRD alone was 0.89 (0.86, 0.92), P < 0.0001, (7.6% in Appendectomy versus 8.6% in controls, at 7.5 years). No subgroup analyses found significantly elevated rates of ADRD in the Appendectomy group. CONCLUSIONS: In this natural experiment involving 329,976 elderly patients, exposure to appendectomy surgery and anesthesia did not increase the subsequent rate of ADRD.

It is of great significance to apply deep learning for the early diagnosis of Alzheimer's disease (AD). In this work, a novel tensorizing GAN with high-order pooling is proposed to assess mild cognitive impairment (MCI) and AD. By tensorizing a three-player cooperative game-based framework, the proposed model can benefit from the structural information of the brain. By incorporating the high-order pooling scheme into the classifier, the proposed model can make full use of the second-order statistics of holistic magnetic resonance imaging (MRI). To the best of our knowledge, the proposed Tensor-train, High-order pooling and Semisupervised learning-based GAN (THS-GAN) is the first work to deal with classification on MR images for AD diagnosis. Extensive experimental results on Alzheimer's disease neuroimaging initiative (ADNI) data set are reported to demonstrate that the proposed THS-GAN achieves superior performance compared with existing methods, and to show that both tensor-train and high-order pooling can enhance classification performance. The visualization of generated samples also shows that the proposed model can generate plausible samples for semisupervised learning purpose.

Introduction It is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognized but can impact on a patient's recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed cognitive impairment in PAD patients. Methods A search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer-reviewed articles examining rates of undiagnosed cognitive impairment in patients with PAD. The following search terms were used: ‘PAD’; ‘PVD’; ‘dementia’; ‘peripheral arterial disease’; ‘peripheral vascular disease’; ‘cognitive impairment'; 'alzheimer's disease’ and ‘cogniti∗’. Our primary outcome was the incidence of previously undiagnosed cognitive impairment in patients with PAD. Results The initial search yielded 1492 titles. After removal of duplicates, 961 abstracts were screened to ascertain if they were eligible for inclusion. Abstract review yielded 62 full texts for further evaluation. Eight case–control studies consisting of 1161 patients were included. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures. Conclusion Our review indicated that PAD patients are more likely to suffer with undiagnosed cognitive impairment than healthy controls.

Objectives The benefit-finding therapeutic (BFT) intervention, training cognitive reappraisal, and alternative thinking to construct positive aspects of caregiving have been found to reduce caregiver depression. This study examines BFT effects on care-recipient outcomes via reduced caregiver depression. Design Cluster-randomized double-blind controlled trial. Setting Social centers and clinics. Participants A total of 129 caregivers. Inclusion criteria were 1) primary caregiver aged 18+, 2) without cognitive impairment, 3) providing ≥14 care hours weekly to a relative with mild-to-moderate Alzheimer's disease, and 4) scoring ≥3 on the Hamilton Depression Rating Scale. Exclusion criterion was care-recipient having Parkinsonism or other forms of dementia. Interventions BFT was evaluated against two forms of psychoeducation—standard and simplified (lectures only) psychoeducation. Measurements Care-recipient outcomes included neuropsychiatric symptoms (NPS), functional impairment, and global dementia severity (Clinical Dementia Rating sum-of-box), measured at baseline, postintervention, and 4- and 10-month follow up. Results Mixed-effects regressions showed a significant effect on NPS when compared with simplified psychoeducation only, with BFT participants reporting fewer NPS (especially mood symptoms) at 4-month follow-up (d = -0.52). Furthermore, longitudinal path analysis (using changes in caregiver depression scores at postintervention to predict changes in care-recipient NPS at follow-up) found that this effect was mediated by improved caregiver depression. No other intervention or mediation effects were found or were consistent across analyses. Conclusions Less depressed caregivers may be able to provide better care and more positive interactions, leading to reduced NPS in care-recipients. However, this benefit of BFT was limited to the comparison with simplified psychoeducation only.

To develop a questionnaire-based Active Mobility Index (AMI) to assess going-out behavior with physical and social activity among older adults, and to assess the criterion-related and predictive validity of the AMI.Prospective cohort study.General community setting. Participants comprised 4432 older adults [mean age: 75.9 ± 4.3 (70-96) years; 2100 men (47.4%)].AMI assessed life-space and activities in each life-space (distance from the respondent's home:1 km, 1-10 km, or10 km) according to physical or social activity during the past 1 month by noting frequency, purpose, type of transportation, interaction with others, and physical activity. Baseline characteristics and outcomes were compared by AMI score quartiles (highest: Q4). To examine the criterion-related validity of AMI, depressive symptoms, frailty, and cognitive function were assessed. During follow-up, incident disability was monitored by Long Term Care Insurance certification.Lower scores (Q1-Q3 groups) were associated with more depressive symptoms, frailty, and cognitive impairment compared with the Q4 group (all P.001). Multiple logistic regression analyses revealed significantly higher odds ratios in the Q1 group in all health adverse outcomes compared with the Q4 group [depressive symptoms, odds ratio (OR) 3.94, 95% confidence interval (CI) 2.95-5.28; frailty, OR 3.20, 95% CI 2.31-4.44; cognitive impairment, OR 1.28, 95% CI 1.04-1.57]. Cox proportional hazards modeling indicated that the Q1 group had a higher risk of incident disability compared with the group (hazard ratio 1.53, 95% CI 1.24-1.88).AMI to assess life-space with physical and social activity among older people was associated with depressive symptoms, frailty, and cognitive impairment. Lower AMI scores were associated with higher incident disability risk. Further studies are needed to elucidate whether AMI is causally associated with incident adverse health outcomes.

Background The Quick Mild Cognitive Impairment (Qmci) test has been suggested to be an easy-to-use and precise screening tool for detecting postoperative cognitive dysfunction (POCD). To provide essential information for future POCD studies in Taiwan, the present study provided data regarding the Taiwan version of the Qmci (Qmci-TW) test conducted in the normative Taiwanese population and changes in them over time. Methods The present study recruited adult native Taiwanese volunteers without known neurologic or psychiatric diseases. All enrolled participants received protocolized serial Qmci-TW test at baseline, 2-day follow-up, and 6-month follow-up. Results In total, 30 participants, 15 men and 15 women, were enrolled in this study. The baseline Qmci-TW score ranged from 55 to 80, with a mean of 68.9 and a standard deviation (SD) of 7. At 2-day follow-up, the mean Qmci-TW test score was significantly higher (by 5.3; SD = 7.3) than that at baseline (P = 0.001). At 6-month follow-up, the mean Qmci-TW score was 71.3 (SD = 6.1), with no significant difference compared with that at baseline. The decline in Qmci-TW scores by > 9 points on postoperative day 1 and by > 11 points at 6-month follow-up was the criterion for POCD. Conclusion The present study provided data regarding the Qmci-TW test conducted in the normative Taiwanese population and its time trajectory during the 6-month follow-up.

A 67-year-old man presented with 5 months of worsening memory impairment and sensory gait ataxia on the background of symptomatic anaemia. He experienced falls, agitation and became socially withdrawn over 3 weeks, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He scored 13/30 on the Montreal Cognitive Assessment. Serum analysis showed normocytic anaemia and leucopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc-containing denture cream was the cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and intravenous and then oral copper supplementation was implemented. Direct questions with regard to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbating pre-existing cognitive impairment.

Although the feasibility of randomized trials for investigating the long-term association between oral health and cognitive decline is low, deriving causal inferences from observational data is challenging. We aimed to investigate the association between poor oral status and subjective cognitive complaints (SCC) using fixed-effects model to eliminate the confounding effect of unobserved time-invariant factors.We used data from Japan Gerontological Evaluation Study (JAGES) which was conducted in 2010, 2013, and 2016. β regression coefficients and 95% confidence intervals [CIs] were calculated using fixed-effects models to determine the effect of deteriorating oral status on developing SCC. Onset of SCC was evaluated using the Kihon Checklist-Cognitive function score. Four oral status variables were used: awareness of swallowing difficulty, decline in masticatory function, dry mouth, and number of teeth.We included 13,594 participants (55.8% women) without SCC at baseline. The mean age was 72.4 (standard deviation [SD], 5.1) years for men and 72.4 (SD, 4.9) years for women. Within the 6-year follow-up, 26.6% of men and 24.9% of women developed SCC. The probability of developing SCC was significantly higher when participants acquired swallowing difficulty (β = 0.088; 95% CI, 0.065-0.111 for men and β = 0.077; 95% CI, 0.057-0.097 for women), decline in masticatory function (β = 0.039; 95% CI, 0.021-0.057 for men and β = 0.030; 95% CI, 0.013-0.046 for women), dry mouth (β = 0.026; 95% CI, 0.005-0.048 for men and β = 0.064; 95% CI, 0.045-0.083 for women), and tooth loss (β = 0.043; 95% CI, 0.001-0.085 for men and β = 0.058; 95% CI, 0.015-0.102 for women).The findings suggest that good oral health needs to be maintained to prevent the development of SCC, which increases the risk for future dementia.

Objective The aim of the study was to explore prevalence, interrelations and accuracy of assessing psychopathology, intelligence, and executive functions (EF) in preschool children with ADHD (age 2.1–6.5 years). Method We prospectively investigated 115 preschool outpatient children (91 boys, 24 girls, aged 4.3 ± 1.0 years) with the clinical diagnosis of ADHD. Assessment included clinical history, background, psychosocial problems (CBCL, C-TRF), ADHD (DISYPS external ratings), cognitive performance (WPPSI-III, K-ABC), and executive functions (BRIEF-P, NEPSY). Results We found a high frequency of dysexecutive problems in up to 64 % in the parental BRIEF-P assessments, up to 62 % in the BRIEF-P teachers’ assessments, and 62 % in the NEPSY functional assessments. Parental and teachers’ BRIEF-P scores were only correlated in one subscale, inhibition, and NEPSY and BRIEF-P were not correlated at all. It was found that 42.5 % of the children with noticeable findings had agreeing results in all three, and another 45 % in two tests. Conclusions About 2/3 of the ADHD preschool children had detectable EF dysfunctions. In order to assess dysexecutive problems, multi-method testing is mandatory.

Aim: The aim of the present study is to investigate the relationship between both functional connectivity and brain networks with cognitive decline, in patients with Parkinson's disease (PD). Introduction: PD phenotype is not limited to motor impairment but, rather, a wide range of non-motor disturbances can occur, with cognitive impairment being one of the most common. However, how the large-scale organization of brain activity differs in cognitively impaired patients, as opposed to cognitively preserved ones, remains poorly understood. Methods: Starting from source-reconstructed resting-state magnetoencephalography data, we applied the phase linearity measurement (PLM) to estimate functional connectivity, globally and between brain areas, in PD patients with and without cognitive impairment (respectively PD-CI and PD-NC), as compared with healthy subjects (HS). Further, using graph analysis, we characterized the alterations in brain network topology and related these, as well as the functional connectivity, to cognitive performance. Results: We found reduced global and nodal PLM in several temporal (fusiform gyrus, Heschl's gyrus, and inferior temporal gyrus), parietal (postcentral gyrus), and occipital (lingual gyrus) areas within the left hemisphere, in the gamma band, in PD-CI patients, as compared with PD-NC and HS. With regard to the global topological features, PD-CI patients, as compared with HS and PD-NC patients, showed differences in multi-frequencies bands (delta, alpha, gamma) in the Leaf fraction, Tree hierarchy (Th) (both higher in PD-CI), and Diameter (lower in PD-CI). Finally, we found statistically significant correlations between the Montreal Cognitive Assessment test and both the Diameter in delta band and the Th in the alpha band. Conclusion: Our work points to specific large-scale rearrangements that occur selectively in cognitively compromised PD patients and are correlated to cognitive impairment. Impact statement In this article, we want to test the hypothesis that the cognitive decline observed in Parkinson's disease (PD) patients may be related to specific changes of both functional connectivity and brain network topology. Specifically, starting from magnetoencephalography signals and by applying the phase linearity measurement (PLM), a connectivity metric that measures the synchronization between brain regions, we were able to highlight differences in the global and nodal PLM values in PD patients with cognitive impairment as compared with both cognitively unimpaired patients and healthy subjects. Further, using graph analysis, we analyzed alterations in brain network topology that were related to cognitive functioning.

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n = 410) and AD (n = 2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.

Molecular chaperones play essential roles in many processes such as cell differentiation, tissue homeostasis, and organ remodeling. Recent data indicate that chaperones can act as cytoprotectants for brain cells during the progression of neurodegenerative diseases, including Alzheimer’s disease (AD). However, very few data on the levels of chaperones in dementia, including its prodromal phases, have been reported. In this study, we used biological samples and epidemiological data collected during the Zabùt Aging Project (a prospective, community-based, cohort study of normal/pathological aging conducted in Sicily, Italy, with a follow-up of ten years) to determine if there is an association between plasma levels of the chaperones Hsp60, Hsp70, and Hsp90 with amnestic mild cognitive impairment (aMCI) and AD. Twenty-six aMCI individuals, 26 AD and 26 controls, matched for age and sex, were enrolled. After adjustment for education, subjects with AD showed significantly higher levels of Hsp60 than aMCI (OR = 1.16, 95% CI 1.04–1.30) and controls (OR = 1.12, 95% CI 1.03–1.22), while Hsp70 was significantly higher only in AD (OR = 1.84, 95% CI 1.09–3.10) than controls. In contrast, circulating levels of Hsp90 were significantly diminished in aMCI (OR = 0.69, 95% CI 0.52–0.91) and AD (OR = 0.51, 95% CI 0.35–0.75) compared to controls. However, these results were no longer significant after adjustment for multiple comparisons. Although the results lost significance after adjustment for multiple comparisons, they are encouraging despite the smallness of the sample and new studies should be carried out with larger populations to determine to what extent sequential measurement of serum chaperones in aMCI and AD can be trusted as indicators of disease status and progression.

Background: The relationship between Alzheimer’s disease (AD) and periodontitis has been recently investigated with heterogenous results. Objective: This study aims to evaluate the oral health status and its relationship with cognitive impairment of participants, enrolled in the Zabút Aging Project, a community-based cohort study performed in a rural community in Sicily, Italy. Methods: A case-control study (20 subjects with AD, 20 with amnestic mild cognitive impairment [aMCI], and 20 controls) was conducted. The protocol included a comprehensive medical and cognitive-behavioral examination. Full-mouth evaluation, microbial analysis of subgingival plaque samples (by RT-PCR analysis), and oral health-related quality of life (OHR-QoL) were evaluated. Results: The decayed, missing, and filled teeth (DMFT) total score of AD subjects was significantly higher than aMCI (p = 0.009) and controls (p = 0.001). Furthermore, the “M” component of DMFT (i.e., the number of missing teeth) was significantly higher in AD than in aMCI (p

Structural magnetic resonance imaging (sMRI)-based Alzheimer's disease (AD) classification and its prodromal stage-mild cognitive impairment (MCI) classification have attracted many attentions and been widely investigated in recent years. Owing to the high dimensionality, representation of the sMRI image becomes a difficult issue in AD classification. Furthermore, regions of interest (ROI) reflected in the sMRI image are not characterized properly by spatial analysis techniques, which has been a main cause of weakening the discriminating ability of the extracted spatial feature. In this study, we propose a ROI-based contourlet subband energy (ROICSE) feature to represent the sMRI image in the frequency domain for AD classification. Specifically, a preprocessed sMRI image is first segmented into 90 ROIs by a constructed brain mask. Instead of extracting features from the 90 ROIs in the spatial domain, the contourlet transform is performed on each of these ROIs to obtain their energy subbands. And then for an ROI, a subband energy (SE) feature vector is constructed to capture its energy distribution and contour information. Afterwards, SE feature vectors of the 90 ROIs are concatenated to form a ROICSE feature of the sMRI image. Finally, support vector machine (SVM) classifier is used to classify 880 subjects from ADNI and OASIS databases. Experimental results show that the ROICSE approach outperforms six other state-of-the-art methods, demonstrating that energy and contour information of the ROI are important to capture differences between the sMRI images of AD and HC subjects. Meanwhile, brain regions related to AD can also be found using the ROICSE feature, indicating that the ROICSE feature can be a promising assistant imaging marker for the AD diagnosis via the sMRI image. Code and Sample IDs of this paper can be downloaded at https://github.com/NWPU-903PR/ROICSE.git.

The current study aimed to evaluate the effects of exercise on negative and cognitive symptoms and simultaneous evaluation of brain and hippocampus volume in patients with schizophrenia. Forty patients with schizophrenia were randomly divided into two groups. The intervention group, in addition to pharmacological treatment, underwent a multi-session exercise program for 8 weeks. At the beginning and end of the study, patients were assessed for cognitive status and negative symptoms using the Mini-Mental State Examination (MMSE) and Positive and Negative Syndrome Scale (PANSS), respectively. Total brain volume and hippocampus volume were also measured using magnetic resonance imaging. Overall, mean MMSE score significantly improved over time, but this improvement was greater in the intervention group (29%) compared to the control group (11%). The same was true for the PANSS negative score (21.5% vs. 53.5%). Absolute hippocampus volume during these 8 weeks, in exercise and control groups, increased from 6.24 to 7.11 and 6.44 to 6.59, respectively. The greater increase in volume obtained in the intervention group was statistically significant ( p = 0.003). Exercise may be associated with improved cognitive function and negative symptoms in patients with schizophrenia; however, additional studies are warranted. [ Journal of Psychosocial Nursing and Mental Health Services, 60 (5), 37–43.]

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (−0.56 points (95% confidence interval: −1.63, 0.52) and −0.89 points (95% confidence interval: −2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Background The number of people diagnosed with dementia worldwide is set to increase significantly. While patients with dementia often have comorbidities, particularly diabetes, patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study aimed to determine whether older people with T2DM exhibit specificity in cognitive function. Methods The Montreal Cognitive Assessment (MoCA) is a well-known tool for examining mild cognitive impairment. The modified Japanese version (MoCA-J) has been confirmed as effective. We conducted an investigative survey to assess the cognitive function of Japanese individuals aged ≥75 years with and without T2DM, using the MoCA-J, and analyzed the results. Results Thirty-three patients with T2DM and 23 non-DM patients completed the examination. Between both groups, a significant difference in the MoCA-J total scores was found. (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM showed scores ≥26, which is the cutoff point for mild cognitive impairment, whereas all patients had the ability of self-care. Additionally, older patients with T2DM had significantly lower delayed recall scores than the non-DM group. Conclusions Patients aged ≥75 years with T2DM might have lower cognition than those without T2DM; the inability to perform delayed recall in T2DM patients might denote a cognitive function decline.Therefore, compared with other patients, patients aged ≥75 years with T2DM need to receive individually tailored explanations about their care, based on their cognition.

BackgroundRecent neuroimaging studies in humans and animal models of Alzheimer’s disease (AD) demonstrated brain hyper-synchrony under amyloid burden, which is being identified as a proxy for conversion to dementia. The potential of non-pharmacological interventions to reverse this neurophysiological phenomenon in the early stages of the disease is still an open question. MethodBrain synchrony modulation by cognitive training (CogTr) was examined in a cohort of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic (MEG) activity and comprehensive neuropsychological scores were acquired before and after completion of a ten-week CogTr program aimed at improving cognitive function and daily living performance. Functional connectivity (FC) analyses were carried out using the phase-locking value. A mixed-effects ANOVA with factors stage (pre-intervention or post-intervention), CogTr (trained or non-trained), and cognitive status (HC or SCD) was used to estimate significant FC changes across MEG recordings.ResultsAlpha-band FC increases were observed for the whole sample (both trained and non-trained), but the effect was different in each group. For the trained group (both HC and SCD), we report a reduction in the FC increase within temporo-parietal and temporo-occipital connections. This effect was particularly manifest in trained participants with SCD, for whom the reduction in the FC increase also correlated with enhanced cognitive performance in different neuropsychological domains (memory, language, and executive function).Conclusions CogTr programs could mitigate the increase in FC observed in preclinical AD, promoting brain synchrony normalization in groups at increased risk for developing the disease.

Background: GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use. Methods: PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol. Results: A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments. Conclusion: These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used and GHB-induced comas occur.

Alzheimer's disease (AD) is one of the deadliest neurodegenerative diseases ailing the elderly population all over the world. An ensemble of Deep learning (DL) models can learn highly complicated patterns from MRI scans for the detection of AD by utilizing diverse solutions. In this work, we propose a computationally efficient, DL-architecture agnostic, ensemble of deep neural networks, named 'Deep Transfer Ensemble (DTE)' trained using transfer learning for the classification of AD. DTE leverages the complementary feature views and diversity introduced by many different locally optimum solutions reached by individual networks through the randomization of hyper-parameters. DTE achieves an accuracy of 99.05% and 85.27% on two independent splits of the large dataset for cognitively normal (NC) vs AD classification task. For the task of mild cognitive impairment (MCI) vs AD classification, DTE achieves 98.71% and 83.11% respectively on the two independent splits. It also performs reasonable on a small dataset consisting of only 50 samples per class. It achieved a maximum accuracy of 85% for NC vs AD on the small dataset. It also outperformed snapshot ensembles along with several other existing deep models from similar kind of previous works by other researchers.

Individuals with mild cognitive impairment are at risk of cognitive and physical decline. Virtual reality (VR) exercise may provide beneficial physical and cognitive exercise. The objectives of this study were to assess the feasibility and safety of home-based VR exercise and to provide pilot data for physical and cognitive efficacy. Eleven individuals with mild cognitive impairment (seven males/four females, average 78 years old, and average 3 years since diagnosis) performed a 30-min home-based VR exercise program 5 days a week for 6 weeks. The VR platform was successfully installed in participants’ homes, and all participants were able to learn the VR program and progress. Participants completed 99% of the prescribed exercise. There were no major adverse events. Most participants enjoyed the VR program and reported physical benefits; fewer reported cognitive benefits. No physical or cognitive outcome measures showed change after 6 weeks. Home-based VR exercise is safe and feasible in individuals with mild cognitive impairment.

Background Cognitive impairment is frequent and disabling in multiple sclerosis (MS). The Brief International Cognitive Assessment in MS (BICAMS) is a recent short battery usable in clinical practice for cognitive evaluation of MS patients. Objective To find cortical areas or brain volumes on magnetic resonance imaging (MRI) structural sequences associated with BICAMS scores in MS. Methods In this cross-sectional single-center study (NCT03656055, September 4, 2018), 96 relapsing remitting-MS patients under natalizumab and without recent clinical or radiological inflammation were included. Patients underwent brain MRI and the three BICAMS tests, evaluating information processing speed (SDMT), visuo-spatial memory (BVMT-R), and verbal memory (FVLT). Results Cortical thickness in the left frontal superior and the right precentral gyri was associated with BVMT-R scores whereas cortical thickness in the left Broca's area and the right superior temporal gyrus was associated with FVLT scores. We observed associations between white matter inflammatory lesions connected to these cortical regions and BICAMS subscores. Conclusions BICAMS scores are associated with specific cortical areas, the cognitive domain matching the known functions of the cortical area. Specific cognitive impairments in MS may be associated with specific cortical regions, themselves influenced by white matter inflammatory lesions and demographical parameters (age, sex, education level).

Background The overall prevalence of headaches decreases with age; however headaches remain frequent in aged individuals who are also affected by other disorders such as cognitive decline. Despite the high frequency of both conditions in these persons, the association between headaches and cognitive decline is underexplored, underdiagnosed and poorly understood. Objective In the present article, we aim to provide a comprehensive review of existing data concerning the link between headache and cognitive decline. Methods We undertook a systematic literature review to report articles that focus on headaches (including all types of headaches) and neurocognitive disorders of degenerative causes. Results Only 9 studies have explored the association between headaches and neurocognitive decline. Methods were highly variable from population-based study to short series of patients using either database or questionnaire during consultation. Studies focusing on Familial Alzheimer's Disease revealed a very high prevalence of headaches in mutation carrier patients compared to non-carrier patients. Conclusion The association between headaches and cognitive decline is underexplored. Future studies are needed to address the pathophysiological mechanisms to improve the treatment of these underestimated headaches.

Machine learning (ML) algorithms play a vital role in brain age estimation frameworks. The impact of regression algorithms on prediction accuracy in the brain age estimation frameworks have not been comprehensively evaluated. Here, we sought to assess the efficiency of different regression algorithms on brain age estimation. To this end, we built a brain age estimation framework based on a large set of cognitively healthy (CH) individuals (N = 788) as a training set followed by different regression algorithms (18 different algorithms in total). We then quantified each regression-algorithm on independent test sets composed of 88 CH individuals, 70 mild cognitive impairment patients as well as 30 Alzheimers disease patients. The prediction accuracy in the independent test set (i.e., CH set) varied in regression algorithms (mean absolute error (MAE) from 4.63 to 7.14 yrs, R2 from 0.76 to 0.88). The highest and lowest prediction accuracies were achieved by Quadratic Support Vector Regression algorithm (MAE = 4.63 yrs, R2 = 0.88, 95% CI = [-1.26, 1.42]) and Binary Decision Tree algorithm (MAE = 7.14 yrs, R2 = 0.76, 95% CI = [-1.50, 2.62]), respectively. Our experimental results demonstrate that prediction accuracy in brain age frameworks is affected by regression algorithms, indicating that advanced machine learning algorithms can lead to more accurate brain age predictions in clinical settings.

There is a limited understanding of the cognitive and psychiatric sequelae of COVID-19 during the post-acute phase, particularly among racially and ethnically diverse patients.We sought to prospectively characterize cognition, mental health symptoms, and functioning approximately four months after an initial diagnosis of COVID-19 in a racially and ethnically diverse group of patients.Approximately four months after COVID-19 diagnosis, patients in the Johns Hopkins Post-Acute COVID-19 Team Pulmonary Clinic underwent a clinical telephone-based assessment of cognition, depression, anxiety, trauma, and function.Most Johns Hopkins Post-Acute COVID-19 Team patients assessed were women (59%) and members of racial/ethnic minority groups (65%). Of 82 patients, 67% demonstrated ≥1 abnormally low cognitive score. Patients requiring intensive care unit (ICU) stays displayed greater breadth and severity of impairment than those requiring less intensive treatment. Processing speed (35%), verbal fluency (26%-32%), learning (27%), and memory (27%) were most commonly impaired. Among all patients, 35% had moderate symptoms of depression (23%), anxiety (15%), or functional decline (15%); 25% of ICU patients reported trauma-related distress. Neuropsychiatric symptoms and functional decline did not differ by post-ICU versus non-ICU status and were unrelated to global cognitive composite scores.At approximately 4 months after acute illness, cognitive dysfunction, emotional distress, and functional decline were common among a diverse clinical sample of COVID-19 survivors varying in acute illness severity. Patients requiring ICU stays demonstrated greater breadth and severity of cognitive impairment than those requiring less intensive treatment. Findings help extend our understanding of the nature, severity, and potential duration of neuropsychiatric morbidity after COVID-19 and point to the need for longitudinal assessment of cognitive and mental health outcomes among COVID-19 survivors of different demographic backgrounds and illness characteristics.

Background Elderly population has been progressively rising in the world, thus the demand for anti-aging heath products to assure longevity as well as to ameliorate age-related complications is also on the rise. Among various anti-aging health products, nicotinamide mononucleotide (NMN) has been gaining attentions of the consumers and the scientific community. Aim of review This article intends to provide an overview on the current knowledge on promises and safety concerns of NMN as an anti-aging health product. Key scientific concepts of review Nicotinamide adenine dinucleotide (NAD+) levels in the body deplete with aging and it is associated with downregulation of energy production in mitochondria, oxidative stress, DNA damage, cognitive impairment and inflammatory conditions. However, NMN, as the precursor of NAD+, can slow down this process by elevating NAD+ levels in the body. A number of in vivo studies have indicated affirmative results of therapeutic effects for various age-induced complications with NMN supplementation. One preclinical and one clinical study have been conducted to investigate the safety concerns of NMN administration while a few more human clinical trials are being conducted. As there is a large influx of NMN based anti-aging products on the market, proper clinical investigations are urgently needed to find out the effectiveness and safety of NMN supplementation.

Background: Acute stress is known to be associated with both negative and positive influences on cognitive performance. Hypertension is one of the risk factors for lowered cognitive performance. Mental stress testing is easier to administer and can be regulated by the investigator. Mental arithmetic using serial subtraction is the most widely used method to administer stress. Reaction time (RT) is widely used to assess cognitive domains like attention, execution and psychomotor speed. Researchers have shown choice reaction times are delayed in hypertension. It is not known whether acute mental stress improves or deteriorates attention, execution and psychomotor speed in hypertension. We hypothesized in the present study that acute mental stress deteriorates cognitive function in hypertensives without overt cerebrovascular disease or other vascular risk factors. Method: After getting medical ethical clearance from our institution, this case-control study was carried out over eight months (January 2017 to September 2017). 60 subjects between the age group of 35 to 55 years were included in the study. They were divided into 2 groups. Group 1 consisted of 30 diagnosed cases of hypertension at least two years of duration. Group 2 consisted of 30 sex and age-matched controls. MMSE was performed to assess the cognitive function in these groups. Simple (S) and choice (C) auditory reaction time (ART) and visual reaction time (VRT)s were measured at rest and acute mental stress in these groups to assess cognitive function. Predictive value of VRTC resting and VRTC during acute mental stress among hypertensives for cognitive dysfunction was calculated using the receiver operating characteristic (ROC) curve. Results: There was significant difference ART and VRT, both simple and choice, in hypertensive and nonhypertensive subjects and these reaction times further increased during mental stress (P Conclusion: A significant difference in cognitive functions in hypertensive and nonhypertensive subjects exists and this further deteriorates with acute mental stress.

Background Exercise is a promising nonpharmacological therapy for cognitive dysfunction, but it is unclear which type of exercise is most effective. The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment (MCI) or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment. Methods We searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia. Primary outcomes included global cognition, executive cognition, and memory cognition. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, and quality of life. Pairwise analyses and network meta-analyses were performed using a random effects model. Results A total of 73 articles from 71 trials with 5606 participants were included. All types of exercise were effective in increasing or maintaining global cognition, and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition: (standard mean difference (SMD) = 1.05, 95% confidence interval (95%CI): 0.56−1.54), executive function (SMD = 0.85, 95%CI: 0.21−1.49), and memory function (SMD = 0.32, 95%CI: 0.01−0.63) in patients with cognitive dysfunction. Subgroup analyses for patients with MCI revealed different effects, and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition (SMD = 0.99, 95%CI: 0.44−1.54) and executive function (SMD = 0.72, 95%CI: 0.06−1.38). However, only resistance exercise showed significant effects on memory function for patients with MCI (SMD = 0.35, 95%CI: 0.01−0.69). Exercise interventions also showed various effects on the secondary outcomes. Conclusion Resistance exercise had the highest probability of being the optimal exercise type for slowing cognitive decline in patients with cognitive dysfunction, especially in patients with dementia. Multicomponent exercise tended to be most effective in protecting global cognition and executive function in patients with MCI.

Purpose Radiation-induced cognitive deficits have a severe negative impact on pediatric brain tumor patients. The severity of cognitive symptoms is related to the age of the child when radiation was applied, with the most severe effects seen in the youngest. Previous studies using whole-brain irradiation (WBRT) in mice confirmed these findings. To understand ipsilateral and contralateral changes in the hippocampus after partial-brain irradiation (PBRT) of the left hemisphere we assessed the neuroplasticity and changes in the microvasculature of the irradiated and non-irradiated hippocampus in juvenile mice. Methods and materials The left hemispheres of 5-week old mice were irradiated with 2, 8, 20 Gray (Gy) and a fractionated dose of 8 Gy in 2 fractions (8 Gy/2f) using a Computed Tomography (CT)-image guided Small Animal Radiation Research Platform (SARRP). Long-Term Potentiation (LTP) has been monitored ex vivo in the hippocampal Cornu Ammonis 1 (CA1) region and was assessed 3 days, 5 and 10 weeks after PBRT in both hemispheres and compared to a sham group. Irradiation effects on the hippocampus microvasculature were quantified by Efficient tissue clearing and Multi-Organ Volumetric Imaging (EMOVI). Results LTP in irradiated hippocampal slices of juvenile mice declines 3 days after radiation, lasts up to 10 weeks in the irradiated part of the hippocampus and correlates with a significantly reduced microvasculature length. Specifically, LTP inhibition is sustained in the irradiated (20 Gy, 8 Gy/2f, 8 Gy, 2 Gy) hippocampus, whereas the contralateral hippocampus remains unaffected after PBRT. LTP inhibition in the irradiated hemisphere after PBRT might be associated with an impaired microvascular network. Conclusion PBRT induces a long-lasting impairment in neuroplasticity and microvessel network of the irradiated hippocampus, whereas the contralateral hippocampus remains unaffected. These findings provide insight into the design of PBRT strategies to better protect the young developing brain from cognitive decline.

Minimal hepatic encephalopathy (MHE) is considered a risk factor for falls in patients with liver cirrhosis. However, MHE is prevalent in patients with muscle alterations (sarcopenia and myosteatosis) probably due to the role of muscle in ammonia handling.To assess the respective role of muscle alterations and MHE on the risk of falls in cirrhotic patients.Fifty cirrhotics were studied for MHE detection by using Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT). CT scan was used to quantify the skeletal muscle index (SMI) and muscle attenuation, as a measure of myosteatosis. The risk of falls was evaluated by the Timed UpGo test (TUG). The occurrence of falls during follow up was also detected.32 patients (64%) had an abnormal TUG (14 s). In the group with TUG ≥ 14 s, MHE (72vs31%, p0.005) and myosteatosis (94vs50%, p = 0.002) were significantly more frequent than in patients with TUG14 s. At multivariate the variables independently associated to TUG ≥ 14 s were myosteatosis, MHE and chronic beta-blockers use. During a mean follow-up of 25±16.9 months, 12 patients fell; the percentage of falls was significantly higher in patients with TUG ≥ 14 s (50%vs9%, p = 0.001) as well as in patients with myosteatosis (33%vs6%, p = 0.03), but similar in patients with or without MHE (35%vs15%, NS).In cirrhotic patients both muscle alterations and cognitive impairment, as well as chronic beta-blockers use, are associated to the risk of falls.

Background The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment. Methods We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery. Results Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function. Conclusions Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology.

Diabetes mellitus is a known risk factor for the development of multiple subtypes of dementia and mild cognitive impairment. Recent research identifies a cause-specific diabetes-related dementia with a unique set of characteristics. Currently, there is no standard cognitive assessment battery recommended to specifically assess dementia that is a direct consequence of chronic diabetes, and some evaluations have been used for decades with minimal revisions, regardless of appropriateness. We performed a systematic review of the dementia/cognition evaluation methods most commonly used in the literature for assessing diabetic patients and identified which cognitive domains are typically assessed in this setting, and whether cognitive changes were more reflective of a vascular pathology, Alzheimer's pathology, or something else entirely. Search results yielded 1,089 articles. After screening for appropriateness, a total of 11 full-text articles were assessed. In general, subjects in the reviewed studies were assessed using a variety of testing methods, examining different combinations of cognitive domains. A standard, clear definition of which cognitive domains are the most important to assess in diabetic patients is needed in order to determine what combination of assessment tools are most pertinent. Given the growing subset of the US population, careful reconsideration of cognitive assessment methods is needed to create self-care plans that take into account a specific collection of cognitive challenges for those with diabetes.

Background: The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with Human T-cell Lymphotropic Virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for the early detection of cognitive impairment in HTLV-1-infected people. Methods: The SMS was measured by a 0-10 visual analog scale combined with a sad-happy faces rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15(21,4%) individuals with HAM/TSP, 20(28,6%) HTLV-1-asymptomatic carriers, and 35(50%) seronegative controls. Results: SMS (p369.0 milliseconds were considered as altered result and indicated cognitive impairment. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significant higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (Conclusion: The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1 infected subjects for everyday memory complaints.

Background and aim Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males. Methods and results 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4±9.2 years; T2D duration 7.6±6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1±0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p=.003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p=0.03). There were no other significant mediators. Conclusion Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.

People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer’s disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; NCI/NNC=934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z5=2.15, p=0.03; I2=98.08%), C-reactive protein (CRP; NCI/NNC=1610/4363, SMD 0.80 [0.50, 1.11], Z14=5.25, p

Leisure activities, particularly physically and cognitively stimulating leisure activities, mitigate cognitive decline. The present study aimed to examine the relationship between mahjong playing, leisure physical activity, and mild cognitive impairment (MCI). Older adults with and without MCI were recruited (n = 489, healthy group; and n = 187, MCI group). The regression results showed that years of mahjong playing (odds ratio = 0.595, 95% confidence interval [0.376, 0.961], p = .032) and physical activity (odds ratio = 0.572, 95% confidence interval [0.381, 0.849], p = .012) were associated with reduced odds of having MCI after adjusting for a series of covariates. Leisure physical activity and mahjong playing interacted with each other and produced combined effects on the odds of having MCI. Combined cognitive and physical interventions may produce larger benefits on cognition than either intervention alone.

Resting-state functional magnetic resonance imaging (rs-fMRI) has become a popular non-invasive way of diagnosing neurological disorders or their early stages by probing functional connectivity between different brain regions of interest (ROIs) across subjects. In the past decades, researchers have proposed many methods to estimate brain functional networks (BFNs) based on blood-oxygen-level-dependent (BOLD) signals captured by rs-fMRI. However, most of the existing methods estimate BFNs under the assumption that signals are independently sampled, which ignores the temporal dependency and sequential order of different time points (or volumes). To address this problem, in this paper, we first propose a novel BFN estimation model by introducing a latent variable to control the sequence of volumes for encoding the temporal dependency and sequential information of signals into the estimated BFNs. Then, we develop an efficient learning algorithm to solve the proposed model by the alternating optimization scheme. To verify the effectiveness of the proposed method, the estimated BFNs are used to identify subjects with mild cognitive impairment (MCIs) from normal controls (NCs). Experimental results show that our method outperforms the baseline methods in the sense of classification performance.

Background: The olfactory system is affected very early in Alzheimer’s disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD. Objective: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors. Methods: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and a passive odor perception task based on magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. Additionally, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation. Conclusion: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.

Background: Cognitive decline is influenced by various factors including diet, cardiovascular disease, and glucose control. However, the combined effect of these risk factors on cognitive performance is yet to be fully understood. Objective: The current study aimed to explore the inter-relationship between these risk factors and cognitive performance in older adults at risk of future cognitive decline. Methods: The sample comprised 163 (Age: M = 65.23 years, SD = 6.50) participants. Food Frequency Questionnaire data was used to score diet quality and adherence to the Western Style Diet (WSD) and Prudent Style Diet (PSD). Glucose control was gauged by serum levels of glycated hemoglobin (HbA1c) and arterial stiffness was measured using carotid to femoral pulse wave velocity. Cognitive performance was assessed using two subtests of the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and Rey’s Verbal Learning Test (RVLT). Results: Diet quality, adherence to the WSD or PSD, and glucose control were not significantly related to cognitive outcomes. However, a significant negative association was found between arterial stiffness and the spatial working memory subtest of SUCCAB (β= –0.21, p

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

Background: Accumulating studies have implicated thyroid dysfunction in the pathogenesis of Alzheimer’s disease (AD). Objective: This study aimed to explore the association between thyroid hormone (TH) levels and cerebrospinal fluid (CSF) biomarkers for AD continuum among euthyroid subjects. Methods: In all, 93 clinically euthyroid subjects with a cognitive decline were included in this prospective cross-sectional study and were divided into groups with abnormal AD biomarkers (belonging to the “Alzheimer’s continuum”; A+ patients) and those with “normal AD biomarkers” or “non-AD pathological changes” (A–patients), according to the ATN research framework classification for AD. A partial correlation analysis of serum thyroid-stimulating hormone (TSH) or TH levels with CSF biomarkers was conducted. The predictor for A+ patients was analyzed via binary logistic regressions. Finally, the diagnostic significance of individual biochemical predictors for A+ patients was estimated via receiver operating characteristic curve analysis. Results: Serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels were found to affect the levels of CSF amyloid-β (Aβ)42 and the ratios of Aβ42/40. Further, FT3 was found to be a significant predictor for A+ via binary logistic regression modeling. Moreover, FT3 showed a high diagnostic value for A+ in euthyroid subjects. Conclusion: Even in a clinical euthyroid state, low serum FT3 and TT3 levels appear to be differentially associated with AD-specific CSF changes. These data indicate that serum FT3 is a strong candidate for differential diagnosis between AD continuum and non-AD dementia, which benefits the early diagnosis and effective management of preclinical and clinical AD patients.

Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuins (SIRT1 – SIRT7) proteins in three study groups: AD, Mild Cognitive Impairment (MCI), and Geriatric Control (GC) by Surface Plasmon Resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3, and SIRT6 levels (mean+SD) were significantly decreased in AD (1.65±0.56, 3.15±0.28, 3.36±0.32ng/µl); compare to MCI (2.17±0.39, 3.60±0.51, 3.73±0.48ng/µl) and GC (2.84±0.47, 4.55±0.48, 4.65±0.55ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in case of other SIRTS between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3, and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.

Background: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. Objective: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. Methods: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. Results: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4) carrier status increased the risk of being Aβ positive (p = 0.002). Conclusion: Degree of HL was not associated with positive Aβ status.

Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4–11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08–1.67; SNAC-K: HR 2.16, 95%CI 1.12–4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.

Background: Superficial white matter (SWM) alterations correlated with cognitive decline have been described in Alzheimer’s disease (AD). Objective: The study aims to extend the investigation of the SWM alterations to AD and non-AD neurodegenerative dementia (ND) and explore the relationship with cerebrospinal fluid (CSF) biomarkers and clinical data. Methods: From a database of 323 suspected dementia cases, we retrospectively recruited 55 ND with abnormal amyloid-β42 (AD) and 38 ND with normal amyloid-β42 (non-AD) and collected clinical data, CSF biomarkers, and magnetic resonance images. Ten healthy controls (HC) were recruited for imaging and Mini-Mental State Examination (MMSE). Diffusion tensor imaging (DTI) measurements were performed in the lobar SWM regions and Kruskal Wallis tests were used for among-group comparison. Spearman’s correlation tests were performed between DTI measures, CSF biomarkers, and clinical data. Results: AD and non-AD showed significant differences in the DTI measures across the SWM compared to HC. Significant differences between AD and non-AD were detected in the left parietal lobe. DTI measures correlated with amyloid-β42 and MMSE diffusely in the SWM, less extensively with total-tau and phosphorylated tau, and with disease duration in the parietal lobe bilaterally. Conclusion: Widespread SWM alterations occur in both AD and non-AD ND and AD shows appreciably more severe alterations in the parietal SWM. Notably, the alterations in the SWM are strongly linked not only to the cognitive decline but also to the diagnostic CSF biomarkers. Further studies are encouraged to evaluate the DTI measures in the SWM as in vivo non-invasive biomarkers in the preclinical phase.

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer’s disease (AD). Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.

Background: Older adults with mild cognitive impairment (MCI) receive fewer guideline-concordant treatments for multiple health conditions than those with normal cognition. Reasons for this disparity are unclear. Objective: To better understand this disparity, we describe physician understanding and experience with patient MCI, particularly physician identification of MCI, ability to distinguish between MCI and dementia, and perspectives on education and training in MCI and dementia. Methods: As part of a mixed-methods study assessing the influence of patient MCI on physician recommendations for acute myocardial infraction and stroke treatments, we conducted a descriptive qualitative study using semi-structured interviews of physicians from three specialties. Key question topics included participants’ identification of MCI, impressions of MCI and dementia awareness within their practice specialty, and perspectives on training and education in MCI. Results: The study included 22 physicians (8 cardiologists, 7 neurologists, and 7 internists). We identified two primary themes: There is 1) a lack of adequate understanding of the distinction between MCI and dementia; and 2) variation in physician approaches to identifying whether an older adult has MCI. Conclusion: These findings suggest that physicians have a poor understanding of MCI. Our results suggest that interventions that improve physician knowledge of MCI are needed.

Background: Down syndrome (DS) is associated with increased risk for Alzheimer’s disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS. Objective: Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS? Methods: Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38–61 years). Results: Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity. Conclusion: Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.