Apathy Predicts Dementia in Cognitively Normal Older People

Severe apathy in cognitively normal older people was tied to an increased risk of future dementia, a prospective study showed.

Compared with older adults who had low levels of apathy, those with severe apathy were nearly twice as likely to develop probable dementia (HR 1.9, 95% CI 1.5-2.5, P<0.001) over 9 years of follow-up, reported Meredith Bock, MD, of the University of California San Francisco, and co-authors.

This relationship remained robust even after adjusting for demographics, cardiovascular risk factors, APOE4 status, and depressed mood (adjusted HR 1.8, 95% CI 1.3-2.3, P<0.001), the researchers wrote in Neurology.

The findings provide novel evidence for apathy as a prodrome of dementia, they said.

Although apathy is correlated with depression, it is distinct with neuroanatomic correlates in the dorsolateral prefrontal cortex and associated sub-regions in the basal ganglia. "While depression has been studied more extensively as a predictor of dementia, our study adds to the research showing that apathy also deserves attention as an independent predictor of the disease," Bock said in a statement.

Apathy is the most common of all the mental health and behavioral symptoms people with dementia experience, noted Clive Ballard, MD, of Exeter University in England, who wasn't involved with the study. "About 50% of people with dementia who have apathy also have depression, but in the other half it is a separate symptom," Ballard said.

"It is very debilitating and has a big impact on people's ability to function day-to-day and take care of themselves, and on the level of care an individual needs," he told MedPage Today. "There are no established drug therapies, but programs to encourage enjoyable activities, enjoyable exercise, and social interaction have been able to demonstrate significant benefits in clinical trials."

Previous studies have suggested that patients with mild cognitive impairment and apathy have a higher incident risk of dementia. "There are no large studies that have investigated apathy as an independent risk factor for or prodrome of dementia in a diverse sample of cognitively normal older adults," the researchers noted.

In their study, Bock and colleagues followed 2,018 white and Black community-dwelling older adults in the NIH's Health, Aging, and Body Composition (Health ABC) cohort. Apathy was assessed in Health ABC by trained staff at an in-person clinic visit using a modified version of the Apathy Evaluation Scale.

The researchers determined incident dementia over 9 years using an algorithm that incorporated dementia medication use, hospital records, or significant global cognitive decline. They also evaluated cognitive change over 5 years with the Modified Mini-Mental State Examination and Digit Symbol Substitution Test.

Mean age of participants was 73.9. Approximately one-third were Black (35.9%) and about half (52.3%) were women. Participants reported an average of 13.3 years of education.

Participants were divided into tertiles based on low, moderate, or severe apathy symptoms: 768 people were in the low apathy group, 742 had moderate apathy, and 508 had severe apathy. Participants with greater apathy at baseline were significantly more likely to be male, Black, and less educated.

During the follow-up period, 381 people developed probable dementia. Severe apathy was associated with an increased risk of dementia compared with low apathy (25% vs 14%). Moderate apathy also was tied to increased dementia risk compared with low apathy, but this relationship was not significant after adjustment.

Greater apathy was associated with worse cognitive score at baseline, but not the rate of cognitive change over time.

The study had several limitations. The algorithm used to determine incident dementia may not be as sensitive as an in-depth physician evaluation, the researchers noted. It also did not allow dementia subtypes to be diagnosed.

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