Understanding the Role of Neuropsychiatric Symptoms in Functional Decline in Alzheimer's Disease

The authors explored classes of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), examined the relationship between NPS classes on rate of functional decline over time, and determined whether effects of individual symptoms on functional decline remained after controlling for NPS classes.

The authors longitudinally analyzed 9,797 study participants with mild cognitive impairment or AD at baseline in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured with the Functional Assessment Questionnaire, and NPSs were assessed by using clinician judgment. Latent class analysis (LCA) was used to identify clusters of individuals who shared similar NPS profiles. Linear mixed models were used to estimate the relationship between NPS classes and individual symptom profiles in functional decline over time.

LCA revealed four distinct NPS classes: an asymptomatic-mild group (48.2% of the sample, N=4,721), a second group predominantly having apathy and depression (36.4%, N=3,562), a third group with high rates of multiple symptoms except for hallucinations (12.8%, N=1,250), and a small group with high rates of all symptoms (complex class, 2.7%, N=264). NPS classes differed in baseline function but were not significantly associated with rate of functional decline. When NPS classes were controlled for, persistent apathy remained strongly associated with a faster rate of functional decline. Effects of apathy were observed across NPS classes and disease severity levels.

Specific symptoms rather than classes of symptoms were associated with the trajectory of functional decline in AD. Apathy may be particularly useful for tracking longitudinal changes in function.