Abstract
ObjectiveTo investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer’s disease (AD).Design and SettingA community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study).Participants3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD.Main Outcome MeasuresCognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults) or an informant (in the sample of prevalent AD patients). Data were analyzed with autoregressive cross-lagged panel analysis.ResultsCognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD.ConclusionsCognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults.
Highlights
Empirical investigation into the temporal ordering of Alzheimer’s disease (AD) signs has largely focused on cerebrospinal fluid and structural magnetic resonance imaging biomarkers [1,2]
We recently demonstrated strong coupling of cognitive and functional declines both between and within patients diagnosed with probable AD [12]
A sample of initially non-demented older adults was drawn from the Washington Heights/Hamilton Heights Inwood Columbia Aging Project (WHICAP) [13,14]
Summary
Empirical investigation into the temporal ordering of Alzheimer’s disease (AD) signs has largely focused on cerebrospinal fluid and structural magnetic resonance imaging biomarkers [1,2]. The concept of mild cognitive impairment (MCI) was proposed to describe early cognitive impairment prior to the manifestation of frank functional loss sufficient to warrant a diagnosis of dementia [3] These MCI criteria required that functional abilities be “essentially normal.”. In recognition of these observations, the most recent recommendations of a National Institute on Aging and Alzheimer’s Association work group explicitly allow for functional problems in the diagnosis of MCI due to AD These new criteria require only that patients “generally maintain their independence of function in daily life, with minimal aids or assistance,” blurring the temporal ordering of cognitive and functional decline in older adults at risk for dementia [7]. This approach allows for an exploration of reciprocal causality between cognition and function
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