Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: the Cache County Dementia Progression study

Abstract

Objectives: Progression of Alzheimer dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains.

Design: Longitudinal, prospective cohort study.

Setting: Cache County (Utah).

Participants: Three hundred twenty-eight persons with a diagnosis of possible/probable AD.

Measurements: Mini-Mental State Exam (MMSE), Clinical Dementia Rating sum-of-boxes (CDR-sb), and Neuropsychiatric Inventory (NPI).

Results: Over a mean follow-up of 3.80 (range: 0.07-12.90) years, the mean (SD) annual rates of change were -1.53 (2.69) scale points on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) on the NPI. Among surviving participants, 30% to 58% progressed less than 1 point per year on these measures, even 5 to 7 years after dementia onset. Rates of change were correlated between MMSE and CDR-sb (r = -0.62, df = 201, p < 0.001) and between the CDR-sb and NPI (r = 0.20, df = 206, p < 0.004). Female subjects (LR χ = 8.7, df = 2, p = 0.013) and those with younger onset (likelihood ratio [LR] χ = 5.7, df = 2, p = 0.058) declined faster on the MMSE. Although one or more apolipoprotein E ε 4 alleles and ever use of FDA-approved antidementia medications were associated with initial MMSE scores, neither was related to the rate of progression in any domain.

Conclusions: A significant proportion of persons with AD progresses slowly. The results underscore differences between population-based versus clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD.

Figure 1

displays individuals identified with dementia from the Cache County Study on Memory in Aging (CCSMA) to the present. Not shown are the CCSMA subjects lost to follow-up between study waves.

Figure 2

displays the trajectories of cognitive (Panel A), functional (Panel B) and NPS (Panel C) domains of dementia. Trajectories in blue represent those whose MMSE slopes fall above the median and red are those that fall below the median. Filled black circles represent individuals with no follow-up. Note the individual in Panel A whose slope falls above the median, but MMSE score is stable at 0. This reflects the relative insensitivity of the MMSE to change in very severe dementia. Inspection of the plots suggests a significant number of individuals decline slowly, with MMSE values at 20 or above at the final observation. The plots also suggest an association between cognitive and functional domains, but little to no association between cognitive and NPS domains. ARC = Annual rate of change.