American Academy of Neurology Abstract

Rate of cognitive decline in Alzheimer's Disease: relationship to clinical and biological factors.

Objective

To calculate rate of cognitive decline in Alzheimer's Disease (AD) using repeated measures analysis methods; to test clinical and biological factors thought to affect progression.

Background

Sporadic AD patients progress at markedly varying rates. Previous studies, suggesting that a variety of factors may influence the rate of progression, are inconsistent.

Design/Methods

267 patients; probable or possible AD; assessed annually at ADRC for 2-9 years; mean initial Mini-Mental State Examination (MMSE) 20.5. Rate of cognitive change (slope) was calculated for the MMSE and Mattis Dementia Rating Scale (DRS), using repeated measures analysis techniques similar to Restricted Maximum Likelihood (REML). Covariates of slope included: initial cognitive score, age, sex, education, APOE genotype and presence/absence of Lewy bodies (LB) at autopsy.

Results

Mean slopes (+- SD) were -3.4 +- 2.9 points per year (MMSE), and -13.1 +- 10.9 (DRS). Slopes correlated strongly with initial scores for both tests. Older age and LB pathology were significantly associated with higher slope; education and gender were not. The APOE e4 allele, although associated with earlier age of onset of AD, did not influence slope.

Conclusions

Annual rate of cognitive change in AD is markedly influenced by initial score. Heterogeneity is further explained by age of onset, and by factors such as LB. APOE strongly affects age at onset of AD, and has a less clear effect on progression.