Enhanced social interaction protects cognition by preserving synapse numbers.

Background: According to the NIA-AA guidelines, pathological diagnosis as Intermedia (I) or High (H) via ABC scores qualifies as pathological Alzheimer's disease (AD). Multiple studies indicated that some individuals, while pathologically diagnosed with AD, maintain normal cognitive function during their lifetime, here defined as resilient AD (rAD). In contrast to typical AD (tAD), characterized by both pathological AD diagnosis and dementia, rAD brains exhibited no significant differences in AD pathology but showed increased synapse numbers. To date, there is limited systematic reporting on the epidemiology and protective factors for rAD.

Methods: This study surveyed reports from multiple global centers to estimate the prevalence of rAD within the pathological AD population. Based on the PUMC Human Brain Bank, I analyzed risk factors and gene mutations associated with dementia severity in pathological AD. Additionally, mouse models were employed to explore the protective effects of enhanced social interaction on cognitive function in pathological AD.

Results: Analysis of multiple global cohorts revealed that rAD accounted for 25-36 % of pathological AD cases. Analysis of the PUMC Human Brain Bank indicated that the severity of dementia in pathological AD was not associated with age or gender. However, the tAD group showed a significantly higher prevalence of social isolation. Genetic analysis suggested that TREM2 rs2234255 GG > CC and APP rs281865161 TC > GG may be risk variants for cognitive impairment in pathological AD, while CLU rs9331896 CC > TT may serve as a protective variant for cognitive resilience. In 5 × FAD mice, increased social interaction did not significantly alter Aβ pathology progression but reduced synaptic loss, thereby improving cognitive function.

Conclusion: These findings suggested that promoting emotional care and social interaction for the elderly may help slow cognitive decline in AD patients.