Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with postmortem neuropathological assessment
PubMed 29480187 · doi:10.3233/JAD-170903
What was done
Data were analyzed from 484 participants in the Religious Orders Study and the Rush Memory and Aging Project who had no cognitive impairment at baseline and later had both a final clinical assessment and postmortem neuropathologic examination. Cognitive decline was measured using a modified Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. Trajectories of functional decline (basic and instrumental activities of daily living) were modeled longitudinally across clinical and neuropathologic AD categories.
What was found
Cognitive and functional decline differed by final clinical diagnosis: participants with AD dementia declined most, those with minor cognitive impairment showed intermediate decline, and those without cognitive impairment declined least. Participants with pathologic AD had significantly more cognitive decline over time than those without, but the difference in overall functional decline between these two groups was small. Handling finances and handling medications were identified as functional domains more sensitive to decline. The abstract reported no exact numerical estimates, test statistics, or p-values.
Why it matters
Because overall functional decline attributable specifically to AD pathology in preclinical stages is small and obscured by non-AD causes of decline, clinical trials of amyloid-targeting drugs require sensitive, domain-specific functional endpoints (such as finance and medication management).
Limits
The abstract provides no exact numerical data, confidence intervals, or effect sizes. The sample is limited to participants who agreed to brain autopsy, introducing potential selection bias, and non-AD contributors to functional impairment were not specifically quantified.
Cited by
- supports In the Religious Orders Study, autopsy examinations revealed that several elderly nuns had physical Alzheimer's disease pathology without showing cognitive deficits during life.