Effects of general medical health on Alzheimer's progression: the Cache County Dementia Progression Study

Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression.

This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI).

Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = -1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01).

Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.