Search

Objectives: We aimed to compare and link the total scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), two common global cognitive screeners., Methods: 2,325 memory clinic patients (63.2 ± 8.6 years; 43% female) with a variety of diagnoses, including subjective cognitive decline, mild cognitive impairment, and dementia due to various etiologies completed the MMSE and MoCA concurrently. We described both screeners, including at the item level. Then, using linear regressions, we investigated how age, sex, education, and diagnosis affected total scores on both instruments. Next, in linear mixed models, we treated the two screeners as repeated measures and analyzed the influence of these characteristics on the relationship between the instruments' total scores. Finally, we linked total scores using equipercentile equating, accounting for relevant patient characteristics., Results: MMSE scores (mean ± standard deviation: 25.0 ± 4.6) were higher than MoCA scores (21.2 ± 5.4), and MMSE items generally showed less variation than MoCA items. Both instruments' scores were individually influenced by age, sex, education, and diagnosis. The relationship between the screeners was moderated by age (estimate = -0.01, 95% confidence interval = [-0.03, -0.00]), education (0.14 [0.10, 0.18]), and diagnosis. These were accounted for when producing crosswalk tables based on equipercentile equating., Conclusions: Accounting for the influence of patient characteristics, we created crosswalk tables to convert MMSE scores to MoCA scores, and vice versa. These tables may facilitate collaboration between clinicians and researchers and could allow larger, pooled analyses of global cognitive functioning in older adults.

Background and Objectives: Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia., Methods: From the Amsterdam Dementia Cohort, we selected amyloid-positive participants with MCI or mild dementia and at least 2 longitudinal Mini-Mental State Examination (MMSE) measurements. Amyloid positivity was based on CSF AD biomarker concentrations or amyloid PET. We used linear mixed modeling to predict MMSE over time, describing trajectories using a cubic time curve and interactions between linear time and the baseline predictors age, sex, baseline MMSE, APOE ε4 dose, CSF β-amyloid (Aβ) 1-42 and pTau, and MRI total brain and hippocampal volume. Backward selection was used to reduce model complexity. These models can predict MMSE over follow-up or the time to an MMSE value. MCI and mild dementia were modeled separately. Internal 5-fold cross-validation was performed to calculate the explained variance ( R 2 )., Results: In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years. Cognitive decline rates increased over time for both MCI and mild dementia (model comparisons linear vs squared vs cubic time fit; p < 0.05 favoring a cubic fit). For MCI, backward selection retained age, sex, and CSF Aβ1-42 and pTau concentrations as time-varying effects altering the MMSE trajectory. For mild dementia, retained time-varying effects were Aβ1-42, age, APOE ε4, and baseline MMSE. R was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aβ1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%.2 was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aβ1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%., Discussion: We constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and the remaining uncertainty and aid in conversations about individualized potential treatment effects.

Objective: The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) is well validated and commonly used to assess difficulties in everyday functioning regarding dementia. To facilitate interpretation and clinical implementation across different European countries, we aim to provide normative data and a diagnostic cutoff for dementia., Methods: Cross-sectional data from Dutch Brain Research Registry ( N = 1,064; mean ( M ) age = 62 ± 11 year; 69.5% female), European Medial Information Framework-Alzheimer's Disease 90 + ( N = 63; Mage = 92 ± 2 year; 52.4% female), and European Prevention of Alzheimer's Dementia Longitudinal Cohort Study ( N = 247; Mage = 63 ± 7 year; 72.1% female) were used. The generalized additive models for location, scale, and shape framework were used to obtain normative values ( Z -scores). The beta distribution was applied, and combinations of age, sex, and educational attainment were modeled. The optimal cutoff for dementia was calculated using area under receiver operating curves (AUC-ROC) and Youden Index, using data from Amsterdam Dementia Cohort ( N = 2,511, Mage = 64 ± 8 year, 44.4% female)., Results: The best normative model accounted for a cubic-like decrease of IADL performance with age that was more pronounced in low compared to medium/high educational attainment. The cutoff for dementia was 1.85 standard deviation below the population mean (AUC = 0.97; 95% CI [0.97-0.98])., Conclusion: We provide regression-based norms for A-IADL-Q and a diagnostic cutoff for dementia, which help improve clinical assessment of IADL performance across European countries.

Introduction: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results., Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System., Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols., Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Instrumental Activities of Daily Living (IADL) limitations are associated with reduced health-related quality of life for people with mild cognitive impairment (MCI). For these people, the assessment of IADL is crucial to the diagnostic process, as well as for the evaluation of new interventions addressing MCI. The Amsterdam IADL Questionnaire Short Version (A-IADL-Q-SV) is an established assessment tool with good psychometric properties that has been shown to be robust to cultural differences in Western countries. The aims of this study were to: (1) cross-culturally adapt and validate the A-IADL-Q-SV for the German-speaking population of Switzerland; (2) investigate its cultural comparability; and (3) evaluate further psychometric properties., Methods: The A-IADL-Q-SV German was pretested on clinicians and participants in a memory clinic setting. The psychometric properties and cultural comparability of the questionnaire were investigated in memory clinic settings including participants with MCI or mild dementia, as well as participants with normal cognition recruited from the community. Item response theory (IRT) was applied to investigate measurement invariance by means of differential item functioning to assess item bias. Additionally, the test-retest reliability on scale level, the construct validity through hypothesis testing and the discriminant validity of the A-IADL-Q-SV German were evaluated., Results: Ninety-six informants of participants with normal cognition, MCI or mild dementia completed the A-IADL-Q-SV German. The basic assumptions for IRT scoring were met. No meaningful differential item functioning for culture was detected between the Swiss and Dutch reference samples. High test-retest reliability on scale level (ICC 0.93; 95% CI 0.9-0.96) was found. More than 75% of the observed correlations between the A-IADL-Q-SV German and clinical measures of cognition and functional status were found to be in the direction and of the magnitude hypothesized. The A-IADL-Q-SV German was shown to be able to discriminate between participants with normal cognition and MCI, as well as MCI and mild dementia., Conclusions: The A-IADL-Q-SV German is a psychometrically robust measurement tool for a Swiss population with normal cognition, MCI and mild dementia. Thus, it provides a valuable tool to assess IADL functioning in clinical practices and research settings in Switzerland. Trial registration This study was registered retrospectively in July 2019 on ClinicalTrials.gov (NCT04012398).

Background: The cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population., Methods: Baseline data of the Capturing Changes in Cognition study was used: an international, prospective cohort study including participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia, and dementia with Lewy bodies (DLB). The CFC comprises seven existing cognitive tests focusing on memory and executive functions (EF) and the informant-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). Construct validity and clinical relevance were assessed by (1) confirmatory factor analyses (CFA) using all CFC subtests and (2) linear regression analyses relating the CFC score (independent) to reference measures of disease severity (dependent), correcting for age, sex, and education. To assess the suitability for the target population, we compared score distributions of the CFC to those of traditional tests (Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, and Clinical Dementia Rating scale)., Results: A total of 184 participants were included (age 71.8 ± 8.4; 42% female; n = 14 SCD, n = 80 MCI, n = 78 AD, and n = 12 DLB). CFA showed that the hypothesized three-factor model (memory, EF, and IADL) had adequate fit (CFI = .931, RMSEA = .091, SRMR = .06). Moreover, worse CFC performance was associated with more cognitive decline as reported by the informant (β = .61, p < .001), poorer quality of life (β = .51, p < .001), higher caregiver burden (β = - .51, p < .001), more apathy (β = - .36, p < .001), and less cortical volume (β = .34, p = .02). Whilst correlations between the CFC and traditional measures were moderate to strong (ranging from - .65 to .83, all p < .001), histograms showed floor and ceiling effects for the traditional tests as compared to the CFC., Conclusions: Our findings illustrate that the CFC has good construct validity, captures clinically relevant aspects of disease severity, and shows no range restrictions in scoring. It therefore provides a more useful outcome measure than traditional tests to evaluate cognition and function in MCI and mild AD.

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia., Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models., Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia., Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Instrumental activities of daily living (IADL) are complex activities which involve multiple cognitive processes, and which are expected to be susceptible to the early effects of cognitive impairment. Informant-based questionnaires are the most common tools used to assess IADL performance in dementia, but must be adjusted for use in early stages of impairment., Objective: To investigate the differences in IADL on the continuum of cognitive decline (i.e. no cognitive decline - subjective cognitive decline - mild cognitive impairment- mild dementia - moderate dementia) using the Spanish version of the Amsterdam IADL Questionnaire (A-IADL-Q)., Methods: A total of 500 volunteer participants were included: 88 participants with no signs of cognitive decline, 109 participants with subjective cognitive complaints, 114 participants with mild cognitive impairment (MCI), 81 participants with mild dementia and 108 participants with moderate dementia. IADL was assessed with the A-IADL-Q, a computerized and adaptive questionnaire that calculates scores according to the specific pattern of responses of each participant. The data were examined by ANOVAs and regression analysis. Multinomial logistic regression analysis was used to evaluate the capacity of the A-IADL-Q to distinguish between diagnostic groups., Results: Participants with no cognitive decline and those with subjective cognitive decline obtained higher A-IADL-Q scores than MCI participants, and participants with MCI obtained higher scores than patients with dementia. The A-IADL-Q showed excellent discrimination between non-cognitive impairment and dementia, and significant but low discrimination between non-cognitive impairment and MCI., Conclusion: A-IADL-Q can discriminate IADL functioning between groups across the dementia spectrum., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Many studies have investigated factors associated with quality of life (QoL) in nursing home residents with dementia. Both pain and neuropsychiatric symptoms (NPS) are clinically relevant and individually associated with a lower QoL; however, there are no studies that investigated pain and NPS together in relation to QoL., Purpose: In this study, we explored the relationship of pain and NPS with QoL in nursing home residents with dementia by investigating the association between pain concurrently with NPS, and QoL., Methods and Patients: Secondary data analyses of cross-sectional data from 199 residents were collected by observations at dementia special care units of 10 nursing homes. QoL was measured with Qualidem, pain with the Mobilization Observation Behavior Intensity Dementia (MOBID-2) Pain Scale and NPS with the Neuropsychiatric Symptoms Inventory. The relation of pain and NPS to QoL was studied using multiple linear regression analyses. Analyses were adjusted for age, sex, activities of daily living, comorbidity, medication use, and dementia severity., Results: Regression models with pain and NPS, showed no independent relationship between pain and QoL subdomains, but NPS, in particular agitation and depressive symptoms, were significantly associated with lower QoL subdomain scores. Agitation was related to lower scores on the subdomains "relationship" [95% confidence interval (CI), -0.083 to -0.059], "positive affect" (95% CI, -0.037 to -0.013), "restless tense behavior" (95% CI, -0.003 to -0.004), and "social relations" (95% CI, -0.033 to -0.009), whereas depression was related to lower scores on the subdomains "positive affect" (95% CI, -0.054 to -0.014), "negative affect" (95% CI, -0.114 to -0.074), "restless tense behavior" (95% CI, -0.075 to -0.025), and "social relations" (95% CI, -0.046 to -0.002)., Conclusions: Only NPS were significantly associated with QoL in nursing home residents with dementia. Further longitudinal research is needed to estimate the nature of the relationship between pain, NPS, and QoL.

Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status.Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a "big data" common data set.We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe.A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries.

Background: Many older people worry about cognitive decline. Early cognitive screening in an anonymous and easily accessible manner may reassure older people who are unnecessarily worried about normal cognitive aging while it may also expedite help seeking in case of suspicious cognitive decline., Objective: To develop and validate online and telephone-based automated self-tests of cognitive function., Methods: We examined the feasibility and validity of the self-tests in a prospective study of 117 participants of whom 34 had subjective cognitive decline (SCD), 30 had mild cognitive impairment (MCI), and 53 had dementia. The ability of these self-tests to accurately distinguish MCI and dementia from SCD was examined with ROC curves. Convergent validity was examined by calculating rank correlations between the self-tests and neuropsychological tests., Results: Both the online and telephone cognitive self-tests were feasible, because the majority of participants (86% and 80%, respectively) were able to complete them. The online self-test had adequate diagnostic accuracy in the screening for MCI and dementia versus SCD with an Area under the Curve (AUC) of 0.86 (95% CI: 0.78-0.93). The AUC of the MMSE was 0.82 (95% CI: 0.74-0.89). By contrast, the telephone self-test had lower diagnostic accuracy (AUC = 0.75, 95% CI: 0.64-0.86). Both self-tests had good convergent validity as demonstrated by moderate to strong rank correlations with neuropsychological tests., Conclusion: We demonstrated good diagnostic accuracy and convergent validity for the online self-test of cognitive function. It is therefore a promising tool in the screening for MCI and dementia.

Introduction: This study aimed to investigate the sensitivity to change over time of a new informant-based instrument to assess instrumental activities of daily living (IADL) during the course of dementia: the Amsterdam IADL Questionnaire(©) (A-IADL-Q)., Methods: Participants (n = 102) were patients and their informants who visited the Alzheimer Center of the VU University Medical Center. Linear mixed models with random effects were used to relate longitudinal change on the A-IADL-Q to diagnosis and to longitudinal change in cognitive measures., Results: We found longitudinal change on the A-IADL-Q to differ between diagnosis (P = .003), with dementia patients showing the fastest rate of decline (P < .001). In addition, we found longitudinal change on the A-IADL-Q to be related to longitudinal change in cognitive measures (global cognition: P < .001; memory: P = .024; executive functioning: P = .028)., Discussion: Findings indicate the A-IADL-Q is sensitive to change over time in IADL functioning and can be used in evaluating treatment effects and assessing individual disease progress., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess how amyloid deposition, glucose hypometabolism, and cerebral atrophy affect neuropsychological performance in patients with Alzheimer disease (AD) dementia, patients with mild cognitive impairment (MCI), and controls over time., Methods: A total of 41 patients with AD dementia, 28 patients with MCI, and 19 controls underwent [(11)C]-Pittsburgh compound B ((11)C-PiB) and [(18)F]-2-fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET and MRI scans at baseline. We extracted global binding potential for (11)C-PiB, the number of abnormal voxels for (18)F-FDG, and gray matter volumes using SIENAX for MRI as measures of amyloid, hypometabolism, and atrophy. In addition, repeat neuropsychological testing was performed, including memory, attention, language, and executive tasks (mean follow-up 2.2 ± 0.7 years). Cross-sectional and longitudinal relationships between imaging markers and cognition were assessed using linear mixed models, including terms for the imaging markers, time, sex, age, diagnosis, and interactions for imaging marker × time and imaging marker × time × diagnosis., Results: Linear mixed models showed that baseline hypometabolism and atrophy were associated with poorer baseline performance on attention and executive functions (p < 0.05), whereas amyloid was not related to baseline cognition. Hypometabolism and amyloid were strongly associated with longitudinal decline in essentially all cognitive domains (pinteraction < 0.05), whereas atrophy was related specifically to future decline in Mini-Mental State Examination and memory (pinteraction < 0.05)., Conclusion: Glucose hypometabolism and brain atrophy were associated with concurrent cognitive function, whereas brain amyloid was not. Amyloid deposition and glucose hypometabolism were predictors for decline of a wide variety of cognitive functions, while brain atrophy specifically predicted memory deterioration., (© 2014 American Academy of Neurology.)

The measurement of instrumental activities of daily living (IADL) is common in clinical practice and research into dementia. IADL are cognitively complex daily activities, such as cooking and doing finances. Their measurement is required for the diagnostic process of dementia, and also useful for the monitoring of disease progression. Since problems in IADL contribute to the disease burden of both patient and caregiver, it is a relevant outcome measure for disease-modifying and non-pharmacological interventions. Despite the widespread use of IADL instruments, an overview of its theoretical background, measurement methods, and potential sources of bias is lacking. In the current manuscript, we therefore aim to provide a selective overview of these topics.

Background: Measuring impairments in "instrumental activities of daily living" (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting., Methods: Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and "disability assessment of dementia" (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses., Results: Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63-0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A-IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not., Conclusions: In this study, we showed a fair diagnostic accuracy for A-IADL-Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool.

Background: This study describes the validation of a new instrument measuring instrumental activities of daily living (IADL), the Amsterdam IADL Questionnaire© (a registered copyright of the Alzheimer Center of the VU University Medical Center). This informant-based tool aimed at detecting IADL problems in incipient dementia was previously found to have a high internal consistency and test-retest reliability., Methods: Patients and their informants who visited the Alzheimer Center of the VU University Medical Center were included in this study. Item response theory was used to estimate the individuals' trait levels as a measure of IADL disability. Construct validity was tested by correlating estimated trait levels with clinical and demographic measures using Pearson's or Kendall's τ correlation coefficients. Additionally, estimated trait levels between patients with and without dementia and between patients with early- and late-onset dementia were compared using independent t tests., Results: A total of 206 informants of patients completed the Amsterdam IADL Questionnaire. The correlations between estimated trait levels and other measures were in concordance with previously formed hypotheses. Patients diagnosed with dementia (n = 93) had higher estimated trait levels than patients without dementia (n = 96), Cohen's effect size, d = 1.04, t(187) = 7.1, p < 0.001. We found no differences between early- and late-onset dementia patients., Conclusions: Results suggest that the Amsterdam IADL Questionnaire is a reliable and valid instrument in the evaluation of dementia., (Copyright © 2013 S. Karger AG, Basel.)

Background: Interference in everyday functioning is part of the diagnostic criteria for dementia. Questionnaires measuring "instrumental activities of daily living" (IADL) are used to measure this interference, but the psychometric quality of these questionnaires is often questioned. In addition, these questionnaires are less suited for early-onset patients. This is problematic, given the high frequency of relatively young patients in memory clinics. In this article, we describe the development and psychometric properties of a new informant-based IADL questionnaire aimed at detecting incipient dementia and appropriate for a broad age range., Methods: We defined IADL in consensus with experts and constructed items based on existing items and suggestions from experts and informants. Informants of subjects (n = 206) who visited the Alzheimer Center of the VU University Medical Center completed the questionnaire. Factor structure was investigated using classical exploratory factor analysis and item response theory. We assessed test-retest reliability in 73 informants using weighted κ values., Results: The questionnaire consisted of 75 items and was computerized to enhance ease of administration. Exploratory factor analysis supported a single-factor model, with 48.3% of the variance being explained by the first factor. We removed five items, as they did not fit the model. High internal consistency was demonstrated. Test-retest reliability showed that the majority of items (87.9%) had substantial-to-almost perfect κ values., Conclusion: The Amsterdam IADL Questionnaire (Amsterdam IADL questionnaire is a registered trademark of Alzheimer Center VU University Medical Center, Amsterdam, The Netherlands) is a 70-item informant-based computerized questionnaire aimed at detecting early dementia and early-onset dementia. Initial results show that this questionnaire is a promising new tool., (Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate whether problems in instrumental activities of daily living (IADL) can add to conventionally used clinical measurements in helping to predict a diagnosis of dementia at 1- and 2-year follow-up., Design: Multicenter prospective cohort study., Setting: Memory clinics in Europe., Participants: Individuals aged 55 and older without dementia., Measurements: IADLs were measured using pooled activities from five informant-based questionnaires. Structural equation modeling (SEM) was used to investigate the relation between IADLs and dementia. Age, sex, education, depression, and cognitive measures (Mini-Mental State Examination and verbal memory) were included in the model., Results: Five hundred thirty-one participants had baseline and 1-year follow-up assessments; 69 (13.0%) of these had developed dementia at 1-year follow-up. At 2-year follow-up, 481 participants were seen, of whom 100 (20.8%) had developed dementia. Participants with IADL disabilities at baseline had a higher conversion rate (24.4%) than participants without IADL disabilities (16.7%) (chi-square = 4.28, degrees of freedom = 1, P = .04). SEM showed that IADL disability could help predict dementia in addition to the measured variables at 1-year follow-up (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.51-3.13) and 2-year follow-up (OR = 2.11, 95% CI = 1.33-3.33)., Conclusion: IADL disability is a useful addition to the diagnostic process in a memory clinic setting, indicating who is at higher risk of developing dementia at 1- and 2-year follow-up., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

IntroductionThere are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100.MethodsParticipant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed.ResultsThe mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI).DiscussionAmong the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

ObjectiveTo demonstrate measurement precision of cognitive domains in the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set.MethodParticipants with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) were included from all ADNI waves. We used data from each person's last study visit to calibrate scores for memory, executive function, language, and visuospatial functioning. We extracted item information functions for each domain and used these to calculate standard errors of measurement. We derived scores for each domain for each diagnostic group and plotted standard errors of measurement for the observed range of scores.ResultsAcross all waves, there were 961 people with NC, 825 people with MCI, and 694 people with AD at their most recent study visit (data pulled February 25, 2019). Across ADNI's battery there were 34 memory items, 18 executive function items, 20 language items, and seven visuospatial items. Scores for each domain were highest on average for people with NC, intermediate for people with MCI, and lowest for people with AD, with most scores across all groups in the range of -1 to +1. Standard error of measurement in the range from -1 to +1 was highest for memory, intermediate for language and executive functioning, and lowest for visuospatial.ConclusionModern psychometric approaches provide tools to help understand measurement precision of the scales used in studies. In ADNI, there are important differences in measurement precision across cognitive domains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

IntroductionThe Dutch Brain Research Registry aims to facilitate online recruitment of participants for brain disease studies.MethodsRegistrants were primarily recruited through an online social media campaign. The registration process included a short questionnaire, which was subsequently used in the prescreening process to match participants to studies.ResultsIn the first 18 months, 17,218 registrants signed up (58±11 years old, 78% female). Out of 34,696 study invitations that were sent, 36% were accepted by registrants, of which 50% to 84% were finally enrolled, resulting in 10,661 participants in 28 studies. Compared to non-participants, study participants were more often older, male, more highly educated, retired or unemployed, non-smoking, healthier, and more often had a family member with dementia.DiscussionThe Dutch Brain Research Registry facilitates effective matching of participants to brain disease studies. Participant factors related to study enrollment may reflect facilitators or barriers for participation, which is useful for improving recruitment strategies.

BackgroundImpairment in daily functioning is a clinical hallmark of dementia. Difficulties with "instrumental activities of daily living" (IADL) seem to increase gradually over the course of Alzheimer's disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD.MethodsIn a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging-Alzheimer's Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized.ResultsThe rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p = .453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = - 0.32 [- 0.55, - 0.09], p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (- 1.06 [- 1.27, - 0.85], p

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Objective: Neuropsychological assessment through VideoTeleConferencing (VTC) can help improve access to diagnostic and follow-up care in memory clinics. This study investigated the stability of performance on VTC assessment in relation to in-person assessment using a test-retest design and explored user experiences of VTC assessment. Materials and Methods: Thirty-one patients (62 ± 6.7 years, 45% female, 58% Subjective Cognitive Decline, 42% Mild Cognitive Impairment/dementia diagnosis) were included from the Amsterdam Dementia Cohort between August 2020 and February 2021. Patients underwent a face-to-face neuropsychological assessment followed by a VTC assessment using the same test protocol within 4 months. Reliability coefficients were calculated using intraclass correlation coefficients (ICC). For each test, the proportion of clinically relevant differences in performances between assessment modalities was calculated. User experiences of patients and neuropsychologists were assessed with questionnaires (User Satisfaction and Ease of use [USE] questionnaire and System Usability Scale [SUS]). Neuropsychologists also participated in a focus group. Results: ICC values were moderate to excellent (0.63-0.93) for all test measures in the total sample. On all tests, most patients did not show clinically relevant performance differences between modalities. Patients and neuropsychologists reported overall positive VTC system usability, although neuropsychologists indicated in the focus group that patients without cognitive impairment required less training for the system and were more independent. Conclusion: VTC assessment showed adequate to excellent test-retest reliability for a broad range of neuropsychological tests commonly used in practice. Assessment through VTC may be a user friendly method in the memory clinic, especially to monitor individuals at risk for future cognitive decline. [ABSTRACT FROM AUTHOR]

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

Introduction: We evaluated determinants associated with care partner outcomes along the Alzheimer's disease (AD) stages. Methods: We included n = 270 care partners of amyloid‐positive patients in the pre‐dementia and dementia stages of AD. Using linear regression analysis, we examined determinants of four care partner outcomes: informal care time, caregiver distress, depression, and quality of life (QoL). Results: More behavioral symptoms and functional impairment in patients were associated with more informal care time and depressive symptoms in care partners. More behavioral symptoms were related with more caregiver distress. Spouse care partners spent more time on informal care and QoL was lower in female care partners. Behavioral problems and subtle functional impairment of the patient predisposed for worse care partner outcomes already in the pre‐dementia stages. Discussion: Both patient and care partner determinants contribute to the care partner outcomes, already in early disease stages. This study provides red flags for high care partner burden. [ABSTRACT FROM AUTHOR]

Introduction: Impaired awareness in dementia caused by Alzheimer's disease and related disorders made study partner-report the preferred method of measuring interference in "instrumental activities of daily living" (IADL). However, with a shifting focus toward earlier disease stages and prevention, the question arises whether self-report might be equally or even more appropriate. The aim of this study was to investigate how participant- and study partner-report IADL perform in a community-based volunteer population without dementia and which factors relate to differences between participant- and study partner-report. Methods: Participants (N = 3,288; 18–97 years, 70.4% females) and their study partners (N = 1,213; 18–88 years, 45.8% females) were recruited from the Dutch Brain Research Registry. IADL were measured using the Amsterdam IADL Questionnaire. The concordance between participant- and study partner-reported IADL difficulties was examined using intraclass correlation coefficient (ICC). Multinomial logistic regressions were used to investigate which demographic, cognitive, and psychosocial factors related to participant and study partner differences, by looking at the over- and underreport of IADL difficulties by the participant, relative to their study partner. Results: Most A-IADL-Q scores represented no difficulties for both participants (87.9%) and study partners (89.4%). The concordance between participants and study partners was moderate (ICC = 0.55, 95% confidence interval [CI] = [0.51, 0.59]); 24.5% (N = 297) of participants overreported their IADL difficulties compared with study partners, and 17.8% (N = 216) underreported difficulties. The presence of depressive symptoms (odds ratio [OR] = 1.31, 95% CI = [1.12, 1.54]), as well as memory complaints (OR = 2.45, 95% CI = [1.80, 3.34]), increased the odds of participants overreporting their IADL difficulties. Higher IADL ratings decreased the odds of participant underreport (OR = 0.71, 95% CI = [0.67, 0.74]). Conclusion: In this sample of community-based volunteers, most participants and study partners reported no major IADL difficulties. Differences between participant and study partner were, however, quite prevalent, with subjective factors indicative of increased report of IADL difficulties by the participant in particular. These findings suggest that self- and study partner-report measures may not be interchangeable, and that the level of awareness needs to be considered, even in cognitively healthy individuals. [ABSTRACT FROM AUTHOR]

Introduction: We estimated the age‐specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE ε4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. [ABSTRACT FROM AUTHOR]

Although the incidence of dementia increases exponentially with age, some individuals reach more than 100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl). The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET-MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation. To date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR 22.0-27.5); most centenarians lived independently, retained hearing and vision abilities and were independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥ 26 points had a mortality percentage of 17% per annual year  in the second year after baseline, while centenarians with a baseline MMSE score < 26 points had a mortality of  42% per annual year (p = 0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60-80 year-old population controls (p = 4.8 × 10−7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p = 6.3 × 10−7). Comprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health. [ABSTRACT FROM AUTHOR]

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD. [ABSTRACT FROM AUTHOR]

Background and objective: There has been a growing interest in using computerized cognitive assessment to detect age-related cognitive disorders. We have developed a tablet-based cancellation test (e-CT), previously shown as a reliable measure of executive functions and free of effect of familiarity with computer-based devices in healthy older adults. This study aimed to investigate the influence of demographics and current daily use of computer-based devices in older adults with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). We further studied the ability of the e-CT to discriminate MCI and AD patients from older adults with normal cognition (NC). Methods: The e-CT was administered to 325 older adults (NC = 112, MCI = 129, AD = 84). Subjects also performed the K-T test, a paper-and-pencil cancellation test from which the e-CT was developed. Multiple linear regression analyses were conducted to assess the contribution of demographics and current daily use of computer-based devices on the e-CT in patient groups. The Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) were established to compare the efficacy of the e-CT and the K-T test to classify subjects into diagnostic groups. Results: In the MCI group, age (B = -0.37, p<0.001) and current daily use of computer-based devices (B = 5.85, p<0.001) were associated with the number of correct cancellations of the e-CT. In the AD group, only current daily use of a computer-based device was a significant contributor (B = 6.28, p<0.001). The e-CT (AUC = 0.811; 95% confidence interval [CI]: 0.756–0.867) and the K-T (AUC = 0.837; CI: 0.787–0.887) showed good and comparable diagnostic accuracy to discriminate between MCI and NC subjects. To discriminate between NC and AD, both tests showed high diagnostic accuracy, with the AUC values of 0.923 (CI: 0.876–0.971) and 0.929 (95%CI: 0.886–0.972) for the e-CT and the K-T, respectively. Conclusion: The e-CT presents satisfying discriminative validity and is a promising tool for detection of early cognitive impairment in older adults. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to investigate the sensitivity to change over time of a new informant-based instrument to assess instrumental activities of daily living (IADL) during the course of dementia: the Amsterdam IADL Questionnaire © (A-IADL-Q). Methods Participants (n = 102) were patients and their informants who visited the Alzheimer Center of the VU University Medical Center. Linear mixed models with random effects were used to relate longitudinal change on the A-IADL-Q to diagnosis and to longitudinal change in cognitive measures. Results We found longitudinal change on the A-IADL-Q to differ between diagnosis ( P = .003), with dementia patients showing the fastest rate of decline ( P < .001). In addition, we found longitudinal change on the A-IADL-Q to be related to longitudinal change in cognitive measures (global cognition: P < .001; memory: P = .024; executive functioning: P = .028). Discussion Findings indicate the A-IADL-Q is sensitive to change over time in IADL functioning and can be used in evaluating treatment effects and assessing individual disease progress. [ABSTRACT FROM AUTHOR]

A decline in everyday cognitive functioning is important for diagnosing dementia. Informant questionnaires, such as the informant questionnaire on cognitive decline in the elderly (IQCODE), are used to measure this. Previously, conflicting results on the IQCODEs ability to discriminate between Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively healthy elderly were found. We aim to investigate whether specific groups of items are more useful than others in discriminating between these patient groups. Informants of 180 AD, 59 MCI, and 89 patients with subjective memory complaints (SMC) completed the IQCODE. To investigate the grouping of questionnaire items, we used a two-dimensional graded response model (GRM).The association between IQCODE, age, gender, education, and diagnosis was modeled using structural equation modeling. The GRM with two groups of items fitted better than the unidimensional model. However, the high correlation between the dimensions (r=.90) suggested unidimensionality. The structural model showed that the IQCODE was able to differentiate between all patient groups. The IQCODE can be considered as unidimensional and as a useful addition to diagnostic screening in a memory clinic setting, as it was able to distinguish between AD, MCI, and SMC and was not influenced by gender or education. (JINS, 2011, 17, 674–681) [ABSTRACT FROM AUTHOR]

Background: Informant questionnaires may be useful in diagnosing early dementia. Conflicting results were found when these questionnaires were used to differentiate patients with mild cognitive impairment (MCI) from healthy elderly subjects. We evaluated the ability of the most commonly used informant questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), to discriminate between Alzheimer's disease (AD), MCI and subjective memory complaints (SMC). Methods: Informants of 180 AD patients, 59 MCI patients and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical Center between 2004 and 2007 completed the short Dutch version of the IQCODE. Logistic regression and receiver operating characteristic curves were used to evaluate the diagnostic ability of the IQCODE. Results: The IQCODE was able to differentiate AD from MCI and SMC, but was not able to differentiate SMC from MCI. Conclusions: The IQCODE may be helpful in diagnosing AD but is of limited use in differentiating MCI from SMC. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is a neurodegenerative disease that presents with profound changes in social cognition. Music might be a sensitive probe for social cognition abilities, but underlying neurobiological substrates are unclear. We performed a meta-analysis of voxel-based morphometry studies in FTD patients and functional MRI studies for music perception and social cognition tasks in cognitively normal controls to identify robust patterns of atrophy (FTD) or activation (music perception or social cognition). Conjunction analyses were performed to identify overlapping brain regions. In total 303 articles were included: 53 for FTD (n = 1153 patients, 42.5% female; 1337 controls, 53.8% female), 28 for music perception (n = 540, 51.8% female) and 222 for social cognition in controls (n = 5664, 50.2% female). We observed considerable overlap in atrophy patterns associated with FTD, and functional activation associated with music perception and social cognition, mostly encompassing the ventral language network. We further observed overlap across all three modalities in mesolimbic, basal forebrain and striatal regions. The results of our meta-analysis suggest that music perception and social cognition share neurobiological circuits that are affected in FTD. This supports the idea that music might be a sensitive probe for social cognition abilities with implications for diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

Abstract Impairment in instrumental activities of daily living (IADL) is an early clinical feature of Alzheimer's disease (AD). The neurobiology underlying IADL disruptions is still unclear. We aimed to investigate the relationship between IADL functioning and cortical atrophy across the AD spectrum. We selected 162 memory-clinic subjects with subjective cognitive decline (n = 49), mild cognitive impairment (n = 26) or AD dementia (n = 87), and an available structural MRI acquired at 3.0 Tesla and Amsterdam IADL Questionnaire (A-IADL-Q) assessment. We used linear regression correcting for age, sex, education, vascular injuries, and total intracranial volume to investigate the association between gray matter volume and A-IADL-Q score, and voxel-based morphometry to investigate whether any associations were specific for distinct regions. Less gray matter volume was associated with lower A-IADL-Q scores (β = 0.346, 95% CI = [0.185-0.507], p < 0.001), specifically in cortical regions covering the medial temporal lobes, cingulate cortex, and precuneus (all p (familywise error–corrected) < 0.05). Results were similar when repeating the analyses in amyloid-positive subjects (n = 78). Our findings illustrate that the A-IADL-Q detects functional impairment related to AD-specific neurodegeneration. Highlights • Worse everyday functioning is related to more cortical atrophy across the AD clinical spectrum. • These associations were specific for anatomical regions known to be involved in AD. • The A-IADL-Q detects functional impairment that can be attributed to AD pathology. [ABSTRACT FROM AUTHOR]