Facilitating clinical use of the Amsterdam Instrumental Activities of Daily Living Questionnaire: Normative data and a diagnostic cutoff value.

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.

Determining the Minimal Important Change of Everyday Functioning in Dementia: Pursuing Clinical Meaningfulness.

BACKGROUND AND OBJECTIVES: Decline in everyday functioning is a key clinical change in Alzheimer disease and related disorders (ADRD). An important challenge remains the determination of what constitutes a clinically meaningful change in everyday functioning. We aimed to investigate this by establishing the minimal important change (MIC): the smallest amount of change that has a meaningful effect on patients' lives. We retrospectively investigated meaningful change in a memory clinic cohort. METHODS: In the first, qualitative part of the study, community-recruited informal caregivers of patients with ADRD and memory clinic clinicians completed a survey in which they judged various situations representing changes in everyday functioning. Their judgments of meaningful change were used to determine thresholds for MIC, both for decline and improvement, on the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. In the second, quantitative part, we applied these values in an independent longitudinal cohort study of unselected memory clinic patients. RESULTS: MIC thresholds were established at the average threshold of caregivers (N = 1,629; 62.4 ± 9.5 years; 77% female) and clinicians (N = 13): -2.2 points for clinically meaningful decline and +5.0 points for clinically meaningful improvement. Memory clinic patients (N = 230; 64.3 ± 7.7 years; 39% female; 60% dementia diagnosis) were followed for 1 year, 102 (45%) of whom showed a decline larger than the MIC, after a mean of 6.7 ± 3.5 months. Patients with a dementia diagnosis and more atrophy of the medial temporal lobe had larger odds (odds ratio [OR] = 3.4, 95% CI [1.5-7.8] and OR = 5.0, 95% CI [1.2-20.0], respectively) for passing the MIC threshold for decline than those with subjective cognitive complaints and no atrophy. DISCUSSION: We were able to operationalize clinically meaningful decline in IADL by determining the MIC. The usefulness of the MIC was supported by our findings from the clinical sample that nearly half of a sample of unselected memory clinic patients showed a meaningful decline in less than a year. Disease stage and medial temporal atrophy were predictors of functional decline greater than the MIC. Our findings provide guidance in interpreting changes in IADL and may help evaluate treatment effects and monitor disease progression.

Giving meaning to the scores of the Amsterdam instrumental activities of daily living questionnaire: a qualitative study.

BACKGROUND: Everyday functioning is a clinically relevant concept in dementia, yet little is known about the clinical meaningfulness of scores on functional outcome measures. We aimed to establish clinically meaningful scoring categories for the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q), representing no, mild, moderate and severe problems in daily functioning. METHODS: Informal caregivers (n = 6) of memory-clinic patients and clinicians (n = 13), including neurologists and nurse specialists, working at various memory clinics in The Netherlands. In focus groups, participants individually ranked nine summaries of fictional patients from least to most impairment in daily functioning. Then, they placed bookmarks to demarcate the thresholds for mild, moderate and severe problems. Individual bookmark placements were then discussed to reach consensus. Clinicians completed a survey in which they placed bookmarks, individually. RESULTS: While individual categorizations varied somewhat, caregivers and clinicians generally agreed on the thresholds, particularly about the distinction between 'no' and 'mild' problems. Score categories were no problems (T-score ≥ 60), mild problems (T-score 50-59), moderate problems (T-score 40-49), and severe problems in daily functioning (T-score < 40), on a scale ranging 20-80. CONCLUSIONS: Our findings provide categories for determining the level of functional impairment, which can facilitate interpretation of A-IADL-Q scores. These categories can subsequently be used by clinicians to improve communication with patients and caregivers.

The Cognitive Online Self-Test Amsterdam (COST-A): Establishing norm scores in a community-dwelling population.

BACKGROUND: Heightened public awareness about Alzheimer's disease and dementia increases the need for at-home cognitive self-testing. We offered Cognitive Online Self-Test Amsterdam (COST-A) to independent groups of cognitively normal adults and investigated the robustness of a norm-score formula and cutoff. METHODS: Three thousand eighty-eight participants (mean age ± standard deviation = 61 ± 12 years, 70% female) completed COST-A and evaluated it. Demographically adjusted norm scores were the difference between expected COST-A scores, based on age, gender, and education, and actual scores. We applied the resulting norm-score formula to two independent cohorts. RESULTS: Participants evaluated COST-A to be of adequate difficulty and duration. Our norm-score formula was shown to be robust: ≈8% of participants in two cognitively normal cohorts had abnormal scores. A cutoff of -1.5 standard deviations proved optimal for distinguishing normal from impaired cognition. CONCLUSION: With robust norm scores, COST-A is a promising new tool for research and clinical practice, providing low cost and minimally invasive remote assessment of cognitive functioning.

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report.

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.

The influence of diversity on the measurement of functional impairment: An international validation of the Amsterdam IADL Questionnaire in eight countries.

INTRODUCTION: To understand the potential influence of diversity on the measurement of functional impairment in dementia, we aimed to investigate possible bias caused by age, gender, education, and cultural differences. METHODS: A total of 3571 individuals (67.1 ± 9.5 years old, 44.7% female) from The Netherlands, Spain, France, United States, United Kingdom, Greece, Serbia, and Finland were included. Functional impairment was measured using the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. Item bias was assessed using differential item functioning (DIF) analysis. RESULTS: There were some differences in activity endorsement. A few items showed statistically significant DIF. However, there was no evidence of meaningful item bias: Effect sizes were low (ΔR 2 range 0-0.03). Impact on total scores was minimal. DISCUSSION: The results imply a limited bias for age, gender, education, and culture in the measurement of functional impairment. This study provides an important step in recognizing the potential influence of diversity on primary outcomes in dementia research.

Latent class analysis identifies functional decline with Amsterdam IADL in preclinical Alzheimer's disease.

INTRODUCTION: Trials in Alzheimer's disease (AD) now include participants at the earliest stages to prevent further decline. However, the lack of tools sensitive to subtle functional changes in early-stage AD hinders the development of new therapies as it is difficult to prove their clinical relevance. METHODS: We assessed functional changes over three years in 289 elderly memory complainers from the Investigation of Alzheimer's Predictors in subjective memory complainers cohort using the Amsterdam Instrumental-Activities-of-Daily-Living questionnaire (A-IADL-Q). RESULTS: No overall functional decline related to AD imaging markers was evidenced. However, five distinct classes of A-IADL-Q trajectories were identified. The largest class (212 [73.4%]) had stable A-IADL-Q scores over 3 years. A second group (23 [8.0%]) showed a persistent functional decline, higher amyloid load (P = .0005), and lower education (P = .0392). DISCUSSION: The A-IADL-Q identified a subtle functional decline in asymptomatic at-risk AD individuals. This could have important implications in the field of early intervention in AD.

Cognitive impairment in patients with multiple sclerosis is associated with atrophy of the inner retinal layers.

BACKGROUND: Inner retinal layer (IRL) atrophy is a potential biomarker for neurodegeneration in multiple sclerosis (MS). OBJECTIVE: To investigate the relationship between cognitive impairment and IRL atrophy in MS. METHODS: Cross-sectional study design, including 217 patients and 59 healthy controls. Subjects were investigated clinically, underwent retinal optical coherence tomography (OCT) and comprehensive cognitive assessments. The association between these modalities was evaluated by regression analyses. RESULTS: Of the patients, 44.2% were cognitively impaired. In the absence of multiple sclerosis-associated optic neuritis (MSON), cognitively impaired patients had a significantly lower mean peripapillary retinal nerve fiber layer (pRNFL, Δ: 8.13 µm, p < 0.001) and mean macular ganglion cell-inner plexiform layer (mGCIPL, Δ: 11.50 µm, p < 0.001) thickness compared to cognitively preserved patients. There was a significant association between the presence of cognitive impairment and pRNFL (odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04-1.18, p = 0.001) and mGCIPL (OR = 1.11, 95% CI = 1.05-1.18, p < 0.001) atrophy. This association was masked by the severe IRL atrophy seen following MSON. CONCLUSION: The strong relationship between cognitive impairment across multiple cognitive domains and atrophy of the pRNFL and mGCIPL in patients who never suffered from MSON suggests that OCT is useful in assessing central nervous system neurodegeneration in MS.