Brain Pathology Adds to Evidence of Link Between Social Activity and Preserved Cognition in Older Adults
Key findings
- This analysis of a clinical–pathologic study of older adults investigated whether aggregation of hyperphosphorylated tau in the locus coeruleus (LC), quantified postmortem, is associated with levels of antemortem social activity and cognitive performance
- Tau aggregation in the LC was associated with lower levels of social activity in the overall sample of 142 participants as well as in the 63 participants who exhibited no cognitive impairment before death
- LC tangle pathology was also associated with lower cognitive performance, and that relationship was partially mediated by late-life level of social activity
- Recognition of decline in social activity and monitoring of LC integrity and neurochemical function might allow early identification of individuals at increased risk of developing Alzheimer's disease
Prior to the accumulation of cerebral amyloid-beta plaques and neurofibrillary tangles of hyperphosphorylated tau that lead to Alzheimer's disease (AD), the bilateral brainstem nuclei that comprise the locus coeruleus (LC) accumulate tau as pre-tangle material. LC tangle density has been negatively correlated with episodic memory function, and it may be a very early marker of vulnerability to AD.
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The LC–noradrenaline system functions with the hypothalamic–pituitary–adrenal system to regulate cognitive, behavioral, and physiologic responses to endogenous and exogenous stresses. Some recent work suggests that the preserved function of the LC–noradrenaline system may be a form of neural reserve that supports cognitive performance even in the presence of neurodegenerative brain changes.
It's also thought that LC-related resilience against cognitive decline might be strengthened by engagement in stimulating cognitive and social activities.
Heidi I. L. Jacobs, PhD, a neuropsychologist/neuroscientist in the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Nancy Donovan, MD, director of the Division of Geriatric Psychiatry at Brigham and Women's Hospital, and colleagues have completed the first investigation of how LC tangle pathology associates with level of social activity. In Molecular Psychiatry, they say early brainstem pathology can affect social function, and the level of social function, in turn, influences cognition before detectable AD.
Methods
Data for this study were drawn from the Rush Memory and Aging Project, an observational study of aging and dementia launched in 1997. Participants underwent annual neuropsychological and clinical assessments and agreed to brain donation at the time of death.
A social activity score was calculated each year from questions about the frequency of going to restaurants, sporting events, or playing bingo; going on day trips or overnight trips; doing unpaid community/volunteer work; visiting relatives' or friends' houses; participating in community groups; and attending religious services. Participants also completed a battery of cognitive function tests and assessments of depressive symptoms and physical activity.
The 142 older adults included in the current analysis had LC pathologic information and social activity measures obtained within one year, on average, before death. The cohort was 69% female, and the median age at death was 89.
At the time of death, a neurologist reviewed all clinical data and rendered a diagnostic opinion about the most likely diagnosis:
- No cognitive impairment (NCI)—63 participants
- Mild cognitive impairment (MCI)—47
- AD dementia—32
Social Activity Analyses
The researchers first examined links between LC tangle density and social activity, adjusting for age, sex, and education:
- Lower LC tangle density was associated with greater social activity (B=−0.05; P=0.023)
- LC tangle density remained associated with social activity when further adjusted for depressive symptoms, amyloid-beta, neurofibrillary tangles, and LC neuronal density (B=−0.06; P=0.033)
- In the NCI group, lower LC tangle density was significantly associated with higher social activity (B=−0.10; P=0.036)
- In the combined MCI and AD dementia groups, LC tangle density and social activity were not significantly associated
Cognition Analyses
When adjusted for age, sex, education and depressive symptoms, better cognitive performance was associated with:
- Lower LC tangle density (B=−0.13; P<0.001)
- Higher social activity score near the end of life (B=0.35; P=0.002)
In mediation analysis, the negative association between LC tangle density and cognitive performance was partially mediated by social activity (B=−0.13; P<0.0001).
The Path Forward
Recognition of neurobehavioral symptoms, such as social decline, and monitoring of LC integrity and neurochemical function might allow early identification of individuals at increased risk of developing AD. These findings should also inform the design of AD prevention trials.
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