The association between low social support and risk of cognitive impairment is partially mediated by neuroanatomic biomarkers of Alzheimer’s disease

Abstract

AbstractBackgroundSocial relationships with less support are linked to greater risk of developing Alzheimer’s disease (AD) and other dementias. Despite growing evidence of this link, to our knowledge, no studies have examined neuropathological processes through which low social support may affect risk of cognitive impairment. We used data from the Women’s Health Initiative Memory Study (WHIMS)‐MRI Study to examine whether neuroanatomical characteristics indicative of AD risk and cerebrovascular diseases underlie the greater risk of cognitive impairment or dementia over time in those with less supportive social relationships.MethodParticipants included 989 women (aged 73‐87 years) from the WHIMS‐MRI study who completed the Medical Outcomes Study Social Support Scale, assessing perceived emotional, tangible, and affectionate support, in 2004‐05. Structural brain scans were performed in 2005‐06 to assess small‐vessel ischemic disease (SVID) volume and determine AD pattern similarity scores (AD‐PS), a brain‐MRI measured neuroanatomical biomarker reflecting diffuse gray matter atrophy in brain regions vulnerable to AD neuropathologies, developed by supervised machine learning and validated with AD Neuroimaging Initiative data. Annual WHIMS follow‐ups included extensive neuropsychological assessments to ascertain centrally‐adjudicated incident cases of mild cognitive impairment (MCI) or all‐cause dementia. Structural equation models were used to assess the association between social support and risk of MCI/dementia (diagnosis data available through June 2018), and whether the association was mediated by global SVID volumes or AD‐PS scores. Models were adjusted for depressive symptoms, demographic, lifestyle, and clinical covariates.ResultLow social support was associated with higher MCI/dementia risk (hazard ratio= 1.23 per 1‐SD; 95% CI: 1.07, 1.44) and also with higher AD‐PS scores (β=.067; 95% CI: .01, .12), but not SVID volume. Higher AD‐PS score accounted for 18.6% (95% CI: 4%, 43%) of the total effect of low social support on risk of MCI/dementia (Figure 1). Higher SVID only accounted for 1.9% (95% CI: ‐1.5%, 8.8%) of the total effect.ConclusionOur study illustrates an association between low social support and higher MCI/dementia risk among older women, which was partly mediated by gray matter atrophy indicative of higher AD risk. Findings also suggest less of a role of cerebrovascular disease in mediating these associations.