Sex-specific neuropsychological correlates of apathy and depression across neurodegenerative disorders

Abstract

Background: Apathy and depression are common neuropsychiatric symptoms across neurodegenerative disorders and are associated with impairment in several cognitive domains, yet little is known about the influence of sex on these relationships.

Objectives: We examined the relationship between these symptoms with neuropsychological performance across a combined cohort with mild or major neurodegenerative disorders, then evaluated the impact of sex.

Design, setting and participants: We conducted a cohort analysis of participants in the COMPASS-ND study with mild cognitive impairment (MCI), vascular MCI, Alzheimer’s disease, mixed dementia, Parkinson’s disease, frontotemporal dementia, and cognitively unimpaired (CU) controls.

Measurements: Participants with neurodegenerative disease and CU controls were stratified by the presence (severity ≥1 on Neuropsychiatric Inventory Questionnaire) of either depressive symptoms alone, apathy symptoms alone, both symptoms, or neither. A neuropsychological battery evaluated executive function, verbal fluency, verbal learning, working memory, and visuospatial reasoning. Analysis of covariance was used to assess group differences with age, sex, and education as covariates.

Results: Groups included depressive symptoms only (n = 70), apathy symptoms only (n = 52), both (n = 68), or neither (n = 262). The apathy and depression + apathy groups performed worse than the neither group on tests of working memory (t(312) = -2.4, p = 0.02 and t(328) = -3.8, p = 0.001, respectively) and visuospatial reasoning (t(301) = -2.3, p = 0.02 and t(321) = -2.6, p = 0.01, respectively). The depression, apathy, and depression + apathy groups demonstrated a similar degree of impairment on tests of executive function, processing speed, verbal fluency, and verbal learning when compared to participants without apathy or depression. Sex-stratified analyses revealed that compared to the male neither group, the male apathy and depression + apathy groups were impaired broadly across all cognitive domains except for working memory. Females with depression alone showed deficits on tests of executive function (t(166) = 2.4, p = 0.01) and verbal learning (t(167) = -4.3, p = 0.001) compared to the female neither group.

Conclusions: This study demonstrated that in neurodegenerative diseases, apathy with or without depression in males was associated with broad cognitive impairments. In females, depression was associated with deficits in executive function and verbal learning. These findings highlight the importance of effectively treating apathy and depression across the spectrum of neurodegenerative disorders with the goal of optimizing neuropsychological outcomes.

Plain Language Summary

Apathy and depression are common symptoms that patients with dementia face during the course of illness. These symptoms are prevalent and often disabling in patients with mild cognitive impairment, Alzheimer’s disease, mixed dementia, Parkinson’s Disease, and Frontotemporal dementia. Studies have shown that people with apathy and depression also suffer from difficulties with memory and learning. Interestingly, researchers have found that while women are more likely to experience depression, men are more likely to suffer from apathy. However, it is not known why these differences exist. We also do not know how memory and learning are affected by the presence of only one (apathy or depression) symptom, as compared to the presence of both.

We set out to examine differences in cognitive performance between patients with apathy alone, depression alone, both, or neither, across groups with mild cognitive impairment, Alzheimer’s disease, mixed dementia, Parkinson’s Disease, and Frontotemporal dementia. Further, we evaluated this relationship within each sex.
We found a patter of differences between males and females, and between having both or only one of the symptoms.

This study demonstrates that in dementia, apathy with or without depression in males is associated with broad cognitive impairments. In females, depression is associated with deficits in several domains. These findings highlight the importance of effectively treating apathy and depression across neurodegenerative disorders with the goal of optimizing cognition.