Functional Activities Questionnaire Research Articles

Assessing clinical progression measures in Alzheimer's disease trials: A systematic review and meta-analysis.

Assessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment. Excluding trials targeting non-cognitive symptoms, we conducted meta-analyses on progression measures from 25 selected RCTs using R version 4.2.0, along with the metafor and emmeans libraries. The Functional Activities Questionnaire (FAQ) demonstrated the greatest sensitivity over 12weeks. Other cognitive measures demonstrated lower sensitivity. The integrated Alzheimer's Disease Rating Scale (iADRS) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) seemed more effective than their individual cognitive components. Neuropsychiatric measures were the least sensitive in measuring progression. Functional measures generally outperformed other measure categories. Purely cognitive domain-based measures were suboptimal for tracking early AD progression. Ideally, future measures should incorporate both cognitive and functional components to enhance sensitivity. Concerns remain regarding the limitations of current outcome measures used in AD clinical trials, particularly their sensitivity in the early and preclinical stages of the disease, which hampers their reliability as indicators of AD progression. The Functional Activities Questionnaire (FAQ) demonstrated the most substantial weighted mean change over 12weeks, followed by the Mini-Mental State Examination (MMSE). Functional measures outperformed other measure categories. Composite scores of integrated Alzheimer's Disease Rating Scale and Clinical Dementia Rating-Sum of Boxes are more sensitive to change than their individual cognitive components, possibly driven by the functional components of the score. Neuropsychiatric measures analyzed in this study appeared to be the least sensitive in measuring progression.

Machine learning models for diagnosing Alzheimer's disease using brain cortical complexity.

This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD). A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidβ-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution (n = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values. The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit. The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results. We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative. Within CN participants with hearing loss, there was a significantly greater rate of cognitive decline per modified preclinical Alzheimer's cognitive composite. Within both CN and MCI participants with hearing loss, there was a significantly greater rate of functional decline per the functional activities questionnaire (FAQ). In CN and MCI participants, hearing loss did not significantly contribute to the risk of progression to a more impaired diagnosis. These results confirm previous studies demonstrating a significant longitudinal association between self-reported hearing loss and cognition/function but do not demonstrate an increased risk of conversion to a more impaired diagnosis. NCT00106899 (ADNI: Alzheimer's Disease Neuroimaging Initiative, clinicaltrials.gov), NCT01078636 (ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity, clinicaltrials.gov), NCT01231971 (ADNI2: Alzheimer's Disease Neuroimaging Initiative 2, clinicaltrials.gov), NCT02854033 (ADNI3: Alzheimer's Disease Neuroimaging Initiative 3, clinicaltrials.gov). Hearing loss is a potential modifiable risk factor for dementia. We assessed the effect of self-reported hearing loss on cognition and function in the ADNI cohort. Hearing loss contributes to significantly faster cognitive and functional decline. Hearing loss was not associated with conversion to a more impaired diagnosis.

A - 131 Patterns of Functional Decline in Alzheimer Biomarker-Positive Vs. Negative Cognitive Impairment

Abstract Objective To contrast longitudinal patterns of functional decline between groups of cognitively impaired individuals with or without biomarker support for Alzheimer’s disease (ad). Method We requested data from the National Alzheimer’s Coordinating Center on individuals who underwent serial evaluation with the Functional Activities Questionnaire (FAQ) and those for whom cerebrospinal fluid biomarkers for ad were available. By cross-referencing the two datasets, we identified 570 subjects, 71 of whom were biomarker positive and 499 biomarker negative. Item-level FAQ item-level scores were then entered as predictor variables into lagged mixed-effects regression models with a single FAQ item as the dependent variable in each model (one model for each of the ten FAQ items). Coefficients for statistically significant predictors of follow-up FAQ items were plotted as arcs on a directed graph, with one vertex for each of the ten FAQ items. We repeated this process for biomarker positive and negative individuals and created a map depicting effect size differences, i.e., biomarker positive minus biomarker-negative regression coefficients (Δ = β + − β-) for statistically significant arcs (α = 0.05). Results Twelve out of 21 arcs that were significant in the biomarker-positive individuals were significant only for this group. The largest effect size difference was STOVE → STOVE (Δ = 0.233). Twenty of 29 arcs that were significant in the biomarker-negative individuals were significant only for this group. The largest effect size difference was GAMES → GAMES (Δ = −0.168). Conclusion ad biomarker status modulated the patterns of longitudinal functional change in this sample.

A - 13 Cognitive Correlates of Technology-Based Instrumental Activities of Daily Living Performance in Older Adults Presenting for Cognitive Evaluations

Abstract Objective Rapid advances in technology have altered how daily activities are performed. Accumulating evidence suggests technology-based instrumental activities of daily living (iADLs) are increasingly common in older adults’ lives, and assessing these skills may improve diagnostic identification of individuals with Alzheimer’s disease and related dementias (ADRD). While iADLs are complex tasks reliant on multiple cognitive processes, prior work suggests memory and executive functioning are the cognitive processes most strongly predictive of iADL performance in ADRD. However, whether similar associations exist with technology-based iADLs has not been established. The goal of the present study was to evaluate the cognitive correlates of technology-based compared to traditional iADL items. Method One hundred seventy-eight individuals (mean age: 75.35 ± 7.30) presenting for evaluation of cognitive status completed tests of memory, executive functioning, language, and processing speed. Care partners completed the Functional Activities Questionnaire (FAQ) and 11 technology-based iADL items. Associations between cognition and traditional and technology-based FAQ items were examined through Pearson’s correlations and multiple regression analyses. Results Cognition was significantly correlated with both traditional and technology-based iADLs (|r’s| > 0.30, p’s.44). In multiple regression models, executive functioning and processing speed but not memory were the strongest predictors of traditional iADL performance (p’s < 0.02), but for independence with technology-based iADLs, executive functioning alone (p < 0.001) emerged. Conclusions Relations between cognition and daily functioning are similar for both traditional and technology-based FAQ items, with executive functioning particularly relevant for both types of tasks. Implications for clinical practice and technology-based interventions are discussed.

Clinical and Neuropathological Correlates of Substance Use in American Football Players.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. To examine the association between substance use and clinical and neuropathological endpoints of CTE. Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04-0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02-0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Among deceased football players, substance use was common and associated with clinical symptoms.

A Novel Score to Predict Individual Risk for Future Alzheimer’s Disease: A Longitudinal Study of the ADNI Cohort

Background: Identifying high-risk individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer’s disease (AD) is crucial for early intervention. Objective: This study aimed to develop and validate a novel clinical score for personalized estimation of MCI-to-AD conversion. Methods: The data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study were analyzed. Two-thirds of the MCI patients were randomly assigned to a training cohort (n = 478), and the remaining one-third formed the validation cohort (n = 239). Multivariable logistic regression was performed to identify factors associated with MCI-to-AD progression within 4 years. A prediction score was developed based on the regression coefficients derived from the logistic model and tested in the validation cohort. Results: A lipidomics-signature was obtained that showed a significant association with disease progression. The MCI conversion scoring system (ranged from 0 to 14 points), consisting of the lipidomics-signature and five other significant variables (Apolipoprotein ɛ4, Rey Auditory Verbal Learning Test immediate and delayed recall, Alzheimer’s Disease Assessment Scale delayed recall test, Functional Activities Questionnaire, and cortical thickness of the AD signature), was constructed. Higher conversion scores were associated with a higher proportion of patients converting to AD. The scoring system demonstrated good discrimination and calibration in both the training cohort (AUC = 0.879, p of Hosmer-Lemeshow test = 0.597) and the validation cohort (AUC = 0.915, p of Hosmer-Lemeshow test = 0.991). The risk classification achieved excellent sensitivity (0.84) and specificity (0.75). Conclusions: The MCI-to-AD conversion score is a reliable tool for predicting the risk of disease progression in individuals with MCI.

The Association of Gabapentin Initiation with Cognitive and Behavioral Changes in Older Adults with Cognitive Impairment: A Retrospective Cohort Study.

Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment. A retrospective cohort study was conducted using the National Alzheimer's Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR®GLOB) or a 1-point increase in CDR® sum of boxes (CDR®SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index+1 and index+2 visits. For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR®GLOB, CDR®SB, FAQ sum, or mean FAQ at the index+1 or index+2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index+2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6]). Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment.

Determinants of sedentary behavior in community-dwelling older adults with type 2 diabetes based on the behavioral change wheel: a path analysis

BackgroundSedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review.MethodsThis cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults’ Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data.ResultsPain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: β = 0.426, β = -0.171, β = -0.209, and β = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients’ SB (total effects: β = -0.180, β = -0.163, and β = 0.127, respectively). All the above pathways were statistically significant (P < 0.05). The path analysis showed that the model had acceptable fit indices: RMSEA = 0.014, χ 2/df = 1.100, GFI = 0.999, AGFI = 0.980, NFI = 0.997, RFI = 0.954, IFI = 1.000, TLI = 0.996, CFI = 1.000.ConclusionCapability (physical function, pain, and cognitive function), opportunity (social isolation, walking environment, and social support), and motivation (social function) were effective predictors of SB in community-dwelling older adults with T2DM. Deeper knowledge regarding these associations may help healthcare providers design targeted intervention strategies to decrease levels of SB in this specific population.

Factors influencing the level of insight and treatment attitude: a cross-sectional study of 141 elderly patients of major depression in Guangzhou, China.

To explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression. A total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function. The sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P<0.05). The various factors were further analyzed by linear regression, revealing that the insight and treatment attitude of elderly depressed hospitalized patients were mainly related to the Mini-Mental State Examination (MMSE) (β= 0.225, 95% CI 0.055-0.395, P=0.01), dependent on a caregiver (β=-5.810, 95% CI -8.086~-3.535, P<0.001), the type of admission (involuntary admission) (β=-3.365, 95% CI -5.448~-1.283, P=0.002), Functional Activities Questionnaire (FAQ) (β=-0.156, 95% CI -0.303~-0.010, P=0.037), and length of stay (≤28 days) (β=2.272, 95% CI 0.055~-4.489, P=0.045). The level of insight was affected by cognitive function, involuntary admission, dependent on a caregiver, social function and length of stay. Future studies should focus on cognitive function recovery, observation of admission mode, and self-care ability in elderly patients with depression.

Simplifying Alzheimer's Disease Monitoring: A Novel Machine-Learning Approach to Estimate the Clinical Dementia Rating Sum of Box Changes Using the Mini-Mental State Examination and Functional Activities Questionnaire.

Primary outcome measure in the clinical trials of disease modifying therapy (DMT) drugs for Alzheimer's disease (AD) has often been evaluated by Clinical Dementia Rating sum of boxes (CDRSB). However, CDR testing requires specialized training and 30-50 minutes to complete, not being suitable for daily clinical practice. Herein, we proposed a machine-learning method to estimate CDRSB changes using simpler cognitive/functional batteries (Mini-Mental State Examination [MMSE] and Functional Activities Questionnaire [FAQ]), to replace CDR testing. Baseline data from 944 ADNI and 171 J-ADNI amyloid-positive participants were used to build machine-learning models predicting annualized CDRSB changes between visits, based on MMSE and FAQ scores. Prediction performance was evaluated with mean absolute error (MAE) and R2 comparing predicted to actual rmDeltaCDRSB/rmDeltayear. We further assessed whether decline in cognitive function surpassing particular thresholds could be identified using the predicted rmDeltaCDRSB/rmDeltayear. The models achieved the minimum required prediction errors (MAE < 1.0) and satisfactory prediction accuracy (R2>0.5) for mild cognitive impairment (MCI) patients for changes in CDRSB over periods of 18 months or longer. Predictions of annualized CDRSB progression>0.5, >1.0, or >1.5 demonstrated a consistent performance (i.e., Matthews correlation coefficient>0.5). These results were largely replicated in the J-ADNI case predictions. Our method effectively predicted MCI patient deterioration in the CDRSB based solely on MMSE and FAQ scores. It may aid routine practice for disease-modifying therapy drug efficacy evaluation, without necessitating CDR testing at every visit.

The relationship between health behaviors and quality of life: the mediating roles of activities of daily living and psychological distress.

The aim of this study is to examine the role of activities of daily living performance (ADLs) and psychological distress in mediating the process by which health behaviors affect QOL. A non-probabilistic study was conducted among 1,065 older adult people older than 60 years. Participants were assessed using the Barthel Index, Functional Activities Questionnaire (FAQ), Kessler Psychological Distress Scale (K10), Australian Active Survey, and EQ-VAS score. The SPSS22.0 software was used to analyze the differences in QOL scores among older adults with different demographic characteristics. Pearson correlation analysis was used to analyze the correlation between health behaviors, psychological distress, ADLs, and QOL. Amos23.0 software was used to construct structural equation model (SEM) to analyze the path of health behavior affecting QOL and the mediating role of BADLs, IADLs and psychological distress. (1) The direct effect of health behaviors on QOL was not significant in the model; (2) ADLs had multiple mediating effects on the relationship between health behaviors and QOL, and the incidence of ADL limitation was negatively correlated with the reported QOL in the older adult; (3) Psychological distress had a significant mediating effect on the relationship between health behaviors and QOL. The results of this study elucidated the mechanisms of the correlation between health behaviors and QOL, and added to the existing literature. In addition, these mediating factors and indirect pathways have been identified as targets for intervention to improve the QOL of older adult individuals, which is important for achieving healthy aging.

Do we all do the same things? Applicability of daily activities at the intersection of demographics.

To evaluate the extent to which demographic factors-and their intersections-influence the applicability of items assessing activities of daily living (ADLs) in a sample of older adults. Participants' (n = 44,713) Functional Activities Questionnaire (FAQ) scores from a multicenter database were evaluated to see how participant and collateral demographics, contextual, and clinical characteristics impacted ADL nonapplicability (NA). Collateral, contextual, and clinical characteristics were matched in those with and without NA. The effect of participant demographics and their interactions on NA responses were modeled with logistic regression. At least one FAQ item (most commonly bill payment, taxes, playing games, and meal preparation) was rated as NA in up to one third of participants across ethnoracial groups. Dementia staging had the largest impact on NA, followed by participant demographics. In a matched sample, logistic models revealed that participant demographics, in particular sex, best predicted NA. However, meaningful interactions with ethnoracial group were noted for bill payment, taxes, meal preparation, and game engagement, suggesting that demographic intersections (e.g., younger vs. older Latinxs) meaningfully predict whether a given ADL was applicable to an individual participant. Neuropsychology is predicated on accurate assessments of both cognition and daily functioning and, in an increasingly diverse aging population, there should be careful consideration of demographic factors, their interactions, and historical contexts that drive day-to-day demands. This study establishes limitations of existing measures and paths forward for creating fair measures of functioning in older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dysexecutive difficulty and subtle everyday functional disabilities: the digital Trail Making Test.

Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B). A total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1-4 (subtle impairment); FAQ = 5-8 (mild impairment). Compared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p < 0.050) and produced more total pen strokes to complete the test (p < 0.016). FAQ-subtle participants required more time to complete the entire test (p < 0.002) and drew individual lines connecting successive target circles slower (p < 0.001) than FAQ-unimpaired participants. Lines connecting successive circle targets were less straight among FAQ-mild, compared to FAQ-unimpaired participants (p < 0.044). Using stepwise nominal regression (reference group = FAQ-unimpaired), pauses inside target circles classified other participants into their respective groups (p < 0.015, respectively). Factor analysis using six dTMT-B variables (oblique rotation) yielded a two-factor solution related to impaired motor/cognitive operations (48.96% variance explained) and faster more efficient motor/cognitive operations (28.88% variance explained). Digital assessment technology elegantly quantifies occult, nuanced behavior not previously appreciated, operationally defines critical underlying neurocognitive constructs related to functional abilities, and yields selected process-based scores that outperform traditional paper/pencil test scores for participant classification. When brought to scale, the dTMT-B test could be a sensitive tool to detect subtle-to-mild functional deficits in emergent neurodegenerative illnesses.

Association between depression, functional capacity, cognitive status and the consumption of fruits and vegetables in elderly in Joinville/SC-Brazil

The consumption of fruits and vegetables seems to contribute to the prevention and/or delay of depression, cognitive decline and, indirectly, to functional dependence, at the same time that it can be influenced by these clinical conditions. The objective of this study was to verify the association between depression, functional capacity, cognitive status and consumption of fruits and vegetables in elderly people in Joinville-SC. A study with secondary data collection carried out in 2021 that assessed depressive symptoms using the Geriatric Depression Scale, functional capacity using the PFEFFER Functional Activities Questionnaire, and cognitive status using the Mini-Mental State Examination. Consumption of fruits and vegetables (FV) was quantified using a food frequency questionnaire and was classified according to regularity. A total of 61 elderly were evaluated, of which 23% had depressive symptoms, 18% functional dependence in instrumental activities of daily living, 14.8% cognitive decline. A low frequency of elderly people with regular consumption of vegetables (36.1%), as well as associated fruits and vegetables (29.5%) was identified. On the other hand, the frequency of regular fruit consumption was high (73.8%) and was associated with a lower frequency of depressive symptoms and functional dependence. It was observed that elderly people with depressive symptoms, functional dependence and cognitive decline consumed FV irregularly.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

Guidelines recommend screening older people (> 60-65years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. We administered MoCA to patients with T2D (age ≥ 60years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Effects of Multicomponent Exercise on Community-Dwelling Older Adults With Mild Cognitive Impairment.

To explore the effects of a group-based multicomponent exercise program on general cognitive functioning, depression, and social functioning in community-dwelling older adults with mild cognitive impairment (MCI) and whether the effects can be maintained. Fifty older adults with MCI were conveniently recruited from two communities in the study area and randomly assigned to the intervention group or control group. The intervention group received three sessions of 60-minute, multicomponent exercise per week for 3 months, plus MCI-related health education. The control group only received MCI-related health education. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Beijing Version (MoCA-BJ) were used to assess general cognitive function. The Functional Activities Questionnaire (FAQ) and Geriatric Depression Scale (GDS-30) were used to evaluate participants' social function and depression, respectively. Participants' exercise intensity was assessed using the Category Ratio Scale. After the 3-month intervention, there were significant improvements in general cognitive function (p = 0.046), attention (p = 0.009), delayed recall (p = 0.015), and social function (p = 0.011) in the intervention group compared with the control group. However, after 3-month postintervention follow up, no significant differences in MMSE, MoCA-BJ, GDS-30, and FAQ scores were noted between groups. The 3-month multicomponent exercise program improved general cognitive function and social functioning in community-dwelling older adults with MCI. However, there was no evidence that these benefits lasted for another 3 months after stopping the exercise program. [Research in Gerontological Nursing, 17(2), 65-79.].

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia. Participants underwent [18F]MK6240 tau-PET, were assigned a PET-based Braak stage at baseline and were followed for a mean (SD) of 1.97 (0.66) years. Functional performance was evaluated with the Functional Activities Questionnaire, Everyday Cognition and functional Clinical Dementia Rating sum of boxes. Multiple linear regressions assessed the association of PET-based Braak stages with baseline functionality and with the longitudinal rate of change in functional scores, adjusting for age, sex and amyloid-β load. We employed voxel-based regression models to investigate the association between functionality and tau-PET signal and assessed the voxel overlap with Braak regions of interest. We included 291 individuals (181 cognitively unimpaired, 56 amyloid-β+ mild cognitive impairment and 54 amyloid-β+ Alzheimer's disease) aged 70.60 (7.48) years. At baseline, PET-based Braak stages III-IV (β = 0.43, P = 0.03) and V-VI (β = 1.20, P < 0.0001) showed associations with poorer Functional Activities Questionnaire scores. Similarly, stages III-IV (β = 0.43, P = 0.02) and V-VI (β = 1.15, P < 0.0001) were associated with worse Everyday Cognition scores. Only stages V-VI were associated with higher functional Clinical Dementia Rating sum of boxes (β = 1.17, P < 0.0001) scores. Increased tau-PET signals in all Braak regions of interest were linked to worse performance in all tools. The voxelwise analysis showed widespread cortical associations between functional impairment and tau-PET and high voxel overlap with Braak regions of interest. Baseline PET-based Braak stages V-VI predicted significant longitudinal functional decline as assessed by the Functional Activities Questionnaire (β = 1.69, P < 0.0001), the Everyday Cognition (β = 1.05, P = 0.001) and the functional Clinical Dementia Rating sum of boxes (β = 1.29, P < 0.0001). Our results suggest that functional impairment increases with the severity of tau accumulation. These findings also indicate that PET-based Braak staging is a good predictor of functional impairment in the Alzheimer's disease continuum. Finally, our study provides evidence for the clinical significance of the PET-based Braak staging framework.

Cortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p<0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p's<0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p= 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p<0.001, meta-cognitional index T score; p=0.002 and Cognitive Difficulties Scale (CDS); p<0.001,) but had an earlier onset age of behavioral (p=0.006) and Parkinsonian motor (p=0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p=0.042), meta-cognition index T score (p=0.014) and age of Parkinsonian motor symptom onset (p=0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF β-amyloid 1-40 (Aβ1-40), β-amyloid 1-42 (Aβ1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aβ1-40/Aβ1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aβ42/Aβ40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.