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Functional assessment in neurocognitive evaluation is often provided via informant reports. These subjective reports can vary based on the characteristics of informants and their relationships with participants, such as informant sex. However, whether informant sex intersects with participant sex to impact subjective ratings of participants' daily functioning, and whether such effects mirror observed patterns in neuropsychological performance, has not been adequately examined with ethnoracially diverse samples. We examined differences among participant-informant sex-based dyads on subjective informant reports of participants' daily functioning (assessed via the Functional Activities Questionnaire [FAQ]), and whether any observed differences on reported functioning corresponded to differences in objective participant performance on neuropsychological performance, among middle-aged and older Hispanic/Latino (n = 543), non-Hispanic Black (NHB; n = 1030), and non-Hispanic White (NHW; n = 5356) adults in the National Alzheimer's Coordinating Center cohort (n = 6929). Analysis of covariance (ANCOVA) tests revealed significant dyad differences on FAQ scores in the NHB (p<.001) and NHW subsamples (p<.05), but not in the Hispanic/Latino subsample (p>.05). For the Hispanic/Latino and NHB subsamples, ANCOVA tests revealed no significant effects of dyad on neuropsychological performance (ps>.01), whereas for the NHW subsample, ANCOVA tests revealed significant dyad differences on performance in multiple cognitive domains (ps<.01). Nevertheless, the pattern of dyad differences on neuropsychological performance did not mirror the pattern of observed differences on FAQ scores in the NHW subsample. Findings and their implications, including potential contributions of other informant characteristics on observed dyad differences on reported functioning, are discussed.

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BACKGROUND: Information on the association between disability and severity of white matter hyperintensities (WMH) among stroke-free individuals is limited. We aimed to assess this association in apparently healthy older adults. METHODS: Following a population-based cross-sectional design, community-dwelling older adults received a brain MRI to grade WMH severity and the Functional Activities Questionnaire to assess the ability to perform activities of daily living. Demographics, clinical risk factors and other markers of cerebral small vessel disease were taken into consideration for analysis. RESULTS: Unadjusted analysis showed a significant association between moderate-to-severe WMH and disability (p = 0.003) that was tempered by the effect of age. Causal mediation analysis showed that age took away 65.9% of the effect of WMH severity on disability. An interaction model showed that disability was higher only among subjects with moderate-to-severe WMH above the median age. CONCLUSIONS: Increasing age mediates the probability of WMH-related disability in stroke-free individuals.

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OBJECTIVE: To evaluate whether the Functional Activities Questionnaire (FAQ), a commonly used measure of functional status in neurodegenerative disease research, performs equivalently across demographically diverse subgroups of participants. METHOD: The FAQs from 30,613 National Alzheimer's Coordinating Center participants were evaluated with a hybrid graded response model-logistic ordinal regression approach to determine the presence of differential item functioning (DIF) within five demographic groups: education, ethnicity, race, language, and sex. RESULTS: Measurable DIF was observed for FAQ items in all groups; however, measures of effect size, latent trait distributions, and item characteristic curves suggested that the impact was minimal for research and practice. CONCLUSIONS: The FAQ is able to provide minimally biased assessments of daily functioning across diverse participants, suggesting potential value for offsetting disparities in diagnosis and treatment.

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OBJECTIVE: To examine the agreement between self- and informant-reported activities of daily living (ADL) deficits in Parkinson's Disease (PD) patients, and to examine factors influencing ADL ratings. BACKGROUND: In PD, the loss of functional independence is an important outcome of disease progression. The valid assessment of ADL function in PD is essential, but it is unclear to what extent informants' and patients' perceptions of their daily functions concur, and how other factors may influence both ratings. METHODS: Data of 150 PD patients who underwent cognitive and motor testing, as well as their informants were analyzed. The 10-item Functional Activities Questionnaire (FAQ), completed separately by patients (FAQ-S) and their informants (FAQ-I), assessed ADL function. Weighted κ statistics summarized level of agreement, and a discrepancy score (FAQ-I - FAQ-S) quantified agreement. Correlation analyses between FAQ total scores, patient and informant characteristics, and cognitive scores were conducted, with post hoc regressions to determine the associations between both FAQ scores and cognition, independent of patient characteristics. RESULTS: The sample included 87 patients with normal cognition, 50 with mild cognitive impairment, and 13 with dementia. Overall, there was fair to moderate agreement between patients and informants on individual FAQ items (0.27 ≤ κ ≤ 0.61, p < 0.004), with greater discrepancies with increasing cognitive impairment. Patients' age, motor severity, non-motor burden, and depression also affected both ratings (0.27 ≤ r ≤ 0.50, p < 0.001), with motor severity showing the greatest influence on both ratings. Both the FAQ-I and FAQ-S were correlated with almost all cognitive domains. Post hoc regression analyses controlling for patient characteristics showed that the attention domain was a significant predictor of both the FAQ-S and FAQ-I scores, and memory was also a significant predictor of the FAQ-I score. Only 29.3% of patients agreed perfectly with informants on the FAQ total score, with informants most commonly rating ADL impairments as more severe than patients. CONCLUSIONS: Patient and informant ratings of ADL function using FAQ items showed moderate agreement, with only few items reaching substantial agreement. Ratings of both were associated with patient cognitive status, but also other characteristics. In addition to patient and informant reports, objective measures are needed to accurately classify ADL deficits in PD.

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The Functional Activities Questionnaire (FAQ) is a collateral-report measure of difficulties in activities of daily living. Despite its widespread use, psychometric analyses have been limited in scope, piecemeal across samples, and limited primarily to classical test theory. This article consolidated and expanded psychometric analyses using tools from generalizability and item response theories among 27,916 individuals from the National Alzheimer's Coordinating Center database who completed the FAQ. Reliability was evaluated with internal consistency, test-retest, and generalizability analyses. Validity was assessed via convergence with neurocognitive measures, classification accuracy with impairment stage, and confirmatory factor and item response theory analyses. Demographics did not impact scores and there was strong evidence for reliability (0.52-0.95), though coefficients were attenuated when restricted in range to diagnostic groups (e.g., normal cognition). There were strong correlations with neurocognitive measures (rs: -.30 to -.59), strong classification accuracy (areas under the curve: .81-.99), and a single-factor model had excellent fit. All items evidenced strong item response theory discrimination and provided significant information regarding functional disability, albeit within a relatively restricted range. The FAQ is a reliable and valid measure of activities of daily living concerns for use in clinical/research settings. It best assesses mild levels of functional difficulty, which is helpful in distinguishing normal cognition from mild cognitive impairment and dementia.

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INTRODUCTION: Cognitive screening measures often lack sensitivity and are hampered by inequities across ethnoracial groups. A multitrait multimethod (MTMM) classification may attenuate these shortcomings. METHODS: A sample of 7227 participants across the diagnostic spectrum were selected from the National Alzheimer's Coordinating Center cohort. Random forest ensemble methods were used to predict diagnosis across the sample and within Black American (n = 1025) and non-Hispanic White groups (n = 5263) based on: (1) a demographically corrected Montreal Cognitive Assessment (MoCA), (2) MoCA and Functional Assessment Questionnaire (FAQ), (3) MoCA and FAQ with demographic correction. RESULTS: The MTMM approach with demographic correction had the highest diagnostic accuracy for the cognitively unimpaired (area under curve [AUC] [95% confidence interval (CI)]): 0.906 [0.892, 0.920]) and mild cognitive impairment (AUC: 0.835 [0.810, 0.860]) groups and reduced racial disparities. DISCUSSION: With further validation, the MTMM approach combining cognitive screening and functional status assessment may serve to improve diagnostic accuracy and extend opportunities for early intervention with greater equity.

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BACKGROUND: Alzheimer's Disease (AD) is a complex and multifactorial disease and novel approaches are needed to illuminate the underlying pathology. Metabolites comprise the end-product of genes, transcripts, and protein regulations and might reflect disease pathogenesis. Blood is a common biofluid used in metabolomics; however, since extracellular vesicles (EVs) hold cell-specific biological material and can cross the blood-brain barrier, their utilization as biological material warrants further investigation. We aimed to investigate blood- and EV-derived metabolites to add insigts to the pathological mechanisms of AD. METHODS: Blood samples were collected from 10 AD and 10 Mild Cognitive Impairment (MCI) patients, and 10 healthy controls. EVs were enriched from plasma using 100,000×g, 1 h, 4 °C with a wash. Metabolites from serum and EVs were measured using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Multivariate and univariate analyses were employed to identify altered metabolites in cognitively impaired individuals. RESULTS: While no significant EV-derived metabolites were found differentiating patients from healthy individuals, six serum metabolites were found important; valine (p = 0.001, fold change, FC = 0.8), histidine (p = 0.001, FC = 0.9), allopurinol riboside (p = 0.002, FC = 0.2), inosine (p = 0.002, FC = 0.3), 4-pyridoxic acid (p = 0.006, FC = 1.6), and guanosine (p = 0.004, FC = 0.3). Pathway analysis revealed branched-chain amino acids, purine and histidine metabolisms to be downregulated, and vitamin B6 metabolism upregulated in patients compared to controls. CONCLUSION: Using a combination of LC-MS and NMR methodologies we identified several altered mechanisms possibly related to AD pathology. EVs require additional optimization prior to their possible utilization as a biological material for AD-related metabolomics studies.

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Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI. Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration's tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach. Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19-2.54, p < 0.01] and activities of daily living (MD -3.08, 95% CI -4.81 to -1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6-3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61-7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I 2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low. Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements. Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820].

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OBJECTIVE: To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia. METHOD: In total, 226 participants (137 females; mean age = 71.76, SD = 7.93; Hispanic Americans = 137; European Americans = 89) were assessed with a comprehensive clinical examination, a neuropsychological battery, a structural magnetic resonance imaging, and were classified as CN or diagnosed with MCI or dementia. Linear regression analyses examined the association between functional activities as measured by the FAQ on brain biomarkers, including HV, ERV, and ERT, controlling for age, education, global cognition, gender, and ethnicity. RESULTS: The FAQ significantly predicted HV, ERV, and ERT for the entire sample. However, this association was not significant for ERV and ERT when excluding the dementia group. The FAQ score remained a significant predictor of HV for the non-dementia group. Age, education, gender, ethnicity, Montreal Cognitive Assessment score, and FAQ were also significant predictors of HV for the overall sample, suggesting that younger Hispanic females with fewer years of education, higher global mental status, and better functioning, were more likely to have larger HV. CONCLUSION: FAQ scores were related to HV in older adults across clinical groups (CN, MCI, and dementia), but its association with the entorhinal cortex was driven by individuals with dementia. Demographic variables, including ethnicity, additionally influenced these associations.

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BACKGROUND AND PURPOSE: To reduce the diagnostic gap of dementia, three strategies can be employed for case finding of cognitive impairment in ambulatory care settings, namely using informant report, brief cognitive test or a combination of informant report and brief cognitive test. The right strategy to adopt across different healthcare settings remains unclear. This diagnostic study compared the performance of the three strategies for detecting dementia (primary aim), as well as for detecting both mild cognitive impairment (MCI) and dementia (secondary aim). METHODS: Participants aged ≥65 years (n = 11 057) were recruited from Alzheimer's Disease Centers across the USA. Participants provided data on an informant report (Functional Activities Questionnaire), brief cognitive test (four-item short variant of Montreal Cognitive Assessment) and a combined measure with informant report and brief cognitive test (sum of Functional Activities Questionnaire and Montreal Cognitive Assessment short variant). They also received standardized assessments (clinical history, physical examination and neuropsychological testing) to diagnose MCI and dementia. Areas under the receiver operating characteristic curve (AUCs) of the three strategies were compared using the DeLong method, with AUC > 90% indicating excellent performance. RESULTS: All three strategies had excellent performance in detecting dementia, although informant report [AUC, 95.9%; 95% confidence intervals (CI), 95.4-96.3%] was significantly better than brief cognitive test (AUC, 93.0%; 95% CI, 92.4-93.6%) and the combined measure had the best performance (AUC, 97.0%; 95% CI, 96.7-97.4%). However, to detect both MCI and dementia, only the combined measure had excellent performance (AUC, 93.0%; 95% CI, 92.5-93.4%), whereas stand-alone informant report or brief cognitive test performed suboptimally (AUC < 90%). Performance of the three strategies was not affected by participants' age, educational attainment or underlying prevalence of MCI and dementia. CONCLUSIONS: For case finding of dementia in ambulatory care settings, informant reports would suffice as first-line measures and brief cognitive tests may optionally be added on, in services with available resources, to further improve the accuracy of detection. For case finding of both MCI and dementia, a combination of informant reports and brief cognitive tests remains the most appropriate strategy.

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The neuropsychological scores and Functional Activities Questionnaire (FAQ) are significant to measure the cognitive and functional domain of the patients affected by the Alzheimer's Disease. Further, there are standardized dataset available today that are curated from several centers across the globe that aid in development of Computer Aided Diagnosis tools. However, there are numerous clinical tests to measure these scores that lead to a challenging task for their assessment in diagnosis. Also, the datasets suffer from common missing and imbalanced data issues. In this paper, we propose a machine learning based framework to overcome these issues. Empirical results demonstrate that improved performance of Genetic Algorithm is obtained for the neuropsychological scores after Miss Forest Imputation and for FAQ scores is obtained after subjecting it to the Synthetic Minority Oversampling Technique.

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The core criterion for Parkinson's disease dementia (PDD) is the impairment in activities of daily living (ADL) function primarily caused by cognitive, not motor symptoms. There is evidence to assume that mild ADL impairments in mild cognitive impairment (PD-MCI) characterize those patients at high risk for dementia. Data of 216 Parkinson's disease (PD) patients assessed with comprehensive motor and neuropsychological assessments were analysed. Based on linear regression models, subscores of the Functional Activities Questionnaire (FAQ) primarily reflecting patients' global cognitive status (FAQC ) or PD-related motor severity (FAQM ) were developed. A quotient (FAQQ ) of both scores was calculated, with values >1 indicating more cognitive- compared to motor-driven ADL impairment. Both FAQC and FAQM scores were higher in PD-MCI than cognitively normal (PD-CN) patients, indicating more severe cognitive- and motor-driven ADL impairments in this group. One third (31.6%) of the PD-MCI group had a FAQQ score >1, which was significantly different from patients with PD-CN (p = .02). PD-MCI patients with an FAQQ score >1 were more impaired on tests assessing attention (p = .019) and language (p = .033) compared to PD-MCI patients with lower FAQQ values. The differentiation between cognitive- and motor-driven ADL is important, as the loss of functional capacity is the defining factor for a diagnosis of PDD. We were able to differentiate the cognitive-driven from the motor-driven ADL impairments for the FAQ. PD-MCI patients with more cognitive- compared to motor-driven ADL impairments may pose a risk group for conversion to PDD and can be targeted for early treatments.

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OBJECTIVES: Within the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s mild cognitive impairment (MCI) cohort, we previously identified MCI subtypes as well as participants initially diagnosed with MCI but found to have normal neuropsychological, biomarker, and neuroimaging profiles. We investigated the functional change over time in these empirically derived MCI subgroups. METHODS: ADNI MCI participants (n=654) were classified using cluster analysis as Amnestic MCI (single-domain memory impairment), Dysnomic MCI (memory+language impairments), Dysexecutive/Mixed MCI (memory+language+attention/executive impairments), or Cluster-Derived Normal (CDN). Robust normal control participants (NCs; n=284) were also examined. The Functional Activities Questionnaire (FAQ) was administered at baseline through 48-month follow-up. Multilevel modeling examined FAQ trajectories by cognitive subgroup. RESULTS: The Dysexecutive/Mixed group demonstrated the fastest rate of decline across all groups. Amnestic and Dysnomic groups showed steeper rates of decline than CDNs. While CDNs had more functional difficulty than NCs across visits, both groups' mean FAQ scores remained below its suggested cutoff at all visits. CONCLUSIONS: Results (a) show the importance of executive dysfunction in the context of other impaired cognitive domains when predicting functional decline in at-risk elders, and (b) support our previous work demonstrating that ADNI's MCI criteria may have resulted in false-positive MCI diagnoses, given the CDN's better FAQ trajectory than those of the cognitively impaired MCI groups. (JINS, 2017, 23, 521-527).

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BACKGROUND: Staging vascular cognitive impairment (VCI) might be useful for sample selection in clinical trials and for guiding clinical decision-making. Clinical dementia rating (CDR) has been applied for staging cognitive impairments of different etiologies, but it may underestimate severity of non-Alzheimer's disease cognitive deficits. METHODS: Out of a total of 147 elderly subjects, 23 (mean age: 72.95 ± 7.51 years; 56% female; mean schooling: 9.52 ± 5.11 years) fulfilled clinical and neuroimaging criteria for VCI. Correlations among cognitive and functional status and scores in CDR and its subsums (CDR Sum of Boxes - CDR-SoB - and CDR Functional Subsum - CDR-FUNC) were performed. RESULTS: Both CDR-SoB and CDR-FUNC correlated with global cognitive performance, functional status, CLOX 2, working memory and abstraction tests. CDR global score only correlated with functional status. DISCUSSION: CDR-FUNC, as well as CDR-SoB, appear to be better indexes of severity in VCI than CDR global score.