Psychometric characteristics of the Amsterdam instrumental activities of daily living questionnaire in healthy individuals and NIA-AA stages of preclinical Alzheimer’s Disease

Background: As clinical trials increasingly focus on the earliest stages of Alzheimer’s disease (AD), there is a need for reliable and valid functional measures in these stages. The National Institute of Aging and Alzheimer’s Association (NIA-AA) defined six clinical stages of AD, with stages 1 and 2 covering preclinical AD with normal cognitive and functional performance. Here, we explored the psychometric characteristics of the Amsterdam Instrumental Activities of Daily Living Questionnaire(A-IADL-Q), separately in stage1-2 AD and amyloid negative controls. Method: Data from four European memory clinic and community-based cohorts (SCIENCe, ALFA+, EPAD-LCS and INSIGHT pre-AD) were jointly analyzed (Fig.1;selection criteria). Amyloid positivity was determined by cerebrospinal fluid or positron-emission tomography, using local cut-offs. We explored three measurement properties:(1) internal consistency, using confirmatory factor analysis and Cronbach’s alpha, (2) construct validity, by correlating A-IADL-Q performance with demographics and neuropsychological tests covering global cognition, executive functions, memory and attention, using Pearson’s r or Kendall’s tau, and (3) responsiveness, using linear mixed modelling with time as variable of interest, adjusted for age, sex and education. Result: A total of 396 controls (mean age = 62±7year, 71% female) and 242 stage1-2 individuals (mean age = 65±9year, 60.7% female) were included (Table1). High internal consistency was supported by a single factor structure (comparative fit index = 0.997, Cronbach’s alpha>0.905). In line with previous validation studies, low correlations were found between A-IADL-Q performance and demographic characteristics. Low correlations were found with neuropsychological test performance (Table2). Regarding responsiveness (N _controls = 219, mean follow-up = 1.45±0.75 year, N _stage1-2 = 127, mean follow-up = 2.16±1.15 year), A-IADL-Q showed a decline in stage1-2, although this did not reach statistical significance (β = -0.1, p = 0.45). Controls showed a small increase in performance, again non-significant (β = 0.06, p = 0.41)(Fig.2). At baseline, stage1-2 individuals had lower A-IADL-Q scores than controls (Welch two-sample t-test: t = -3.13, p<0.01). Conclusion: Our findings support the psychometric characteristics of the A-IADL-Q in stage1-2 individuals and controls. Construct validity was partially supported, as expected, because cognitive impairments are not evident in this population. In line with this, findings regarding responsiveness may have been affected by the short follow-up time of one year. Future validation in preclinical AD should include a longer follow-up duration, to adequately capture potential decline.