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Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework.
Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.
1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001).
We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
Commonly used measures of instrumental activities of daily living (IADL) do not capture activities for a technologically advancing society. This study aimed to adapt the proxy/informant-based Amsterdam IADL Questionnaire (A-IADL-Q) for use in the UK and develop a self-report version.
An iterative mixed method cross-cultural adaptation of the A-IADL-Q and the development of a self-report version involving a three-step design: (1) interviews and focus groups with lay and professional stakeholders to assess face and content validity; (2) a questionnaire to measure item relevance to older adults in the U.K.; (3) a pilot of the adapted questionnaire in people with cognitive impairment.
Community settings in the UK.
One hundred and forty-eight participants took part across the three steps: (1) 14 dementia professionals; 8 people with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia due to Alzheimer’s disease; and 6 relatives of people with MCI or dementia; (2) 92 older adults without cognitive impairment; and (3) 28 people with SCD or MCI.
The cultural relevance and applicability of the A-IADL-Q scale items were assessed using a 6-point Likert scale. Cognitive and functional performance was measured using a battery of cognitive and functional measures.
Iterative modifications to the scale resulted in a 55-item adapted version appropriate for UK use (A-IADL-Q-UK). Pilot data revealed that the new and revised items performed well. Four new items correlated with the weighted average score (Kendall’s Tau −.388, −.445, −.497, −.569). An exploratory analysis of convergent validity found correlations in the expected direction with cognitive and functional measures.
The A-IADL-Q-UK provides a measurement of functional decline for use in the UK that captures culturally relevant activities. A new self-report version has been developed and is ready for testing. Further evaluation of the A-IADL-Q-UK for construct validity is now needed.
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