Loneliness is a state of perceived social and emotional isolation that has been associated with cognitive and functional decline and with a doubling of the risk of Alzheimer's disease (AD) dementia. Furthermore, loneliness has been shown to increase dementia risk while controlling for depression and objective measures of social support and social ties. Biological pathways linking loneliness and cognitive decline in the elderly are unknown. This study will examine loneliness as a putative, early psychosocial marker of AD and will address the possibility that changes in social cognition, such as loneliness, may be associated with connectivity disruptions in the default mode network (DMN) linked to early AD related pathology and clinical decline. The goal of this study is to determine whether measures of loneliness are associated with sensitive neuropsychological tests and multi-modal neuroimaging biomarkers of preclinical AD in a cohort of clinically normal (CN) older adults, participating in the ongoing Harvard Aging Brain Study (HABS). CN elderly are a heterogeneous group of individuals without overt cognitive impairment, including a subset with preclinical AD. HABS is a newly established, National Institute on Aging funded, 5-year observational study of community dwelling, CN elderly, who are assessed for the presence of AD biomarkers and are monitored intensively for cognitive decline. The proposed study will add clinical evaluations for loneliness and objective measures of social network and support in a subset of 100 CN participants and will assess the cross-sectional relationship of these measures to depression, to sensitive cognitive assessments and to existing functional magnetic resonance imaging (fMRI) and Pittsburgh Compound B positron emission tomography (PiB-PET) amyloid imaging to address the following 3 specific aims: 1) To examine the relation of loneliness measures to cognitive function while adjusting for depression, objective social ties and known factors affecting cognitive decline, 2) To investigate whether loneliness is associated with brain network disruption as assessed with resting-state fMRI, 3)To examine the relation of loneliness to cortical amyloid burden, as measured by PiB PET. This study will define changes in cognition related to loneliness, elucidate alterations in neural networks associated with loneliness in older individuals, and will examine loneliness in relation to known biomarkers of the AD pathway. This proposal will advance the understanding of two debilitating conditions often associated with aging, loneliness and AD, which are rarely studied together. By using multi-modal neuroimaging, multi-dimensional clinical evaluations and social epidemiological tools we can address the biological basis of the loneliness construct in elderly at risk for AD and the interaction of social and cognitive health with the earliest manifestations of AD.

Public Health Relevance

This study will extend our understanding of loneliness and its potential relevance to early clinical detection and diagnosis of Alzheimer's disease (AD) and it will inform effective interventions for loneliness in older individuals. This work responds to NIA strategic goal A-1 to support basic research in the psychological science of aging to understand the pathways and mechanisms through which psychological and social factors impact health and also supports strategic goal C-1 to refine our knowledge of molecular, cellular, cognitive and other behavioral changes that cause or accompany development of AD and other dementias of aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
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Wagster, Molly V
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Brigham and Women's Hospital
United States
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Donovan, Nancy J; Wu, Qiong; Rentz, Dorene M et al. (2017) Loneliness, depression and cognitive function in older U.S. adults. Int J Geriatr Psychiatry 32:564-573
Donovan, Nancy J; Okereke, Olivia I; Vannini, Patrizia et al. (2016) Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults. JAMA Psychiatry 73:1230-1237
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