Greater cognitive reserve is related to lower cortical excitability in healthy cognitive aging, but not in early clinical Alzheimer’s disease

OBJECTIVE: To investigate the relationship between cortico-motor excitability and cognitive reserve (CR) in cognitively unimpaired older adults (CU) and in older adults with mild cognitive impairment or mild dementia due to Alzheimer’s disease (AD). METHODS: Data were collected and analyzed from 15 CU and 24 amyloid-positive AD participants aged 50–90 years. A cognitive reserve questionnaire score (CRQ) assessed education, occupation, leisure activities, physical activities, and social engagement. Cortical excitability was quantified as the average amplitude of motor evoked potentials (MEP amplitude) elicited with single-pulse transcranial magnetic stimulation delivered to primary motor cortex. A linear model compared MEP amplitudes between groups. A linear model tested for an effect of CRQ on MEP amplitude across all participants. Finally, separate linear models tested for an effect of CRQ on MEP amplitude within each group. Exploratory analyses tested for effect modification of demographics, cognitive scores, atrophy measures, and CSF measures within each group using nested regression analysis. RESULTS: There was no between-group difference in MEP amplitude after accounting for covariates. The primary model showed a significant interaction term of group*CRQ (R(2)(adj) = 0.18, p = 0.013), but no main effect of CRQ. Within the CU group, higher CRQ was significantly associated with lower MEP amplitude (R(2)(adj) = 0.45, p = 0.004). There was no association in the AD group. CONCLUSION: Lower cortico-motor excitability is related to greater CRQ in CU, but not in AD. Lower MEP amplitudes may reflect greater neural efficiency in cognitively unimpaired older adults. The lack of association seen in AD participants may reflect disruption of the protective effects of CR. Future work is needed to better understand the neurophysiologic mechanisms leading to the protective effects of CR in older adults with and without neurodegenerative disorders.