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Anxious-depressive symptoms an early sign of Alzheimer’s in cognitively normal elderly

Elevated amyloid beta levels were associated with increasing anxious-depressive symptoms among older adults with normal cognitive health and may predict preclinical Alzheimer’s disease, according to study results.

Prior research collected from multiple epidemiological studies has demonstrated that cognitively normal older adults with neuropsychiatric symptoms, especially depression-related symptoms and anxiety, are twice as likely to develop amnestic mild cognitive impairment compared with those without these symptoms, according to the researchers.

“Recent findings suggest that cognitively normal older individuals with biomarker evidence of amyloidosis (principally high fibrillar brain amyloid beta levels) are more likely to experience rising depressive symptoms over time,” Nancy J. Donovan, MD, from Brigham and Women’s Hospital, and colleagues wrote. “At the same time, these preliminary observations raise more pointed questions as to the quality, severity, and time course of depressive symptoms that are most characteristic of preclinical Alzheimer’s disease and the specificity of their associations with Alzheimer’s molecular markers.”

Researchers examined the associations of brain amyloid beta burden and longitudinal measures of depression and depressive symptom clusters in 270 community-dwelling, cognitively normal older adults to understand how depressive symptoms affect preclinical Alzheimer’s disease. They assessed continuous Pittsburgh compound B (PiB) binding as a predictor of depression using the Geriatric Depression Scale (GDS) total score and scores for three GDS clusters — apathy-anhedonia, dysphoria and anxiety-concentration — over a 5-year period. Predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E 4 status, depression history and interactions with time.

In total, 13% of the participants reported current or past depression. Older adults with a history of depression had a significantly higher mean baseline PiB binding compared with those with no depression history. The results showed that older adults with a history of depression had a higher adjusted mean GDS score over the 5-year period vs. those without depression. There was a significant difference in mean PiB binding between adults with no depression history compared with adults with current depression (1.16 and 1.28; P = .006) but not compared with those with past depression (1.16 and 1.22; P = .2).

“These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and provide support for the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer’s disease,” Donovan and colleagues wrote. “Further longitudinal follow-up is necessary to determine whether these escalating depressive symptoms give rise to clinical depression and/or [mild cognitive impairment] and dementia stages of Alzheimer’s disease over an extended period.” – by Savannah Demko

Disclosures: Donovan has received salary support from Eisai and Eli Lilly; her spouse is employed by Alkermes. Please see the study for all other authors’ relevant financial disclosures.