Neurophysiological and brain structural markers of cognitive frailty differs from Alzheimer’s disease

With increasing life span, there is growing importance of understanding the mechanisms of successful cognitive ageing. In contrast, cognitive frailty has been proposed to be a precursor to Alzheimer’s disease. Here we test the hypothesis that cognitively frail adults represent a branch of healthy ageing, distinct from latent dementia. We used electro-magnetoencephalography and magnetic resonance imaging to investigate the structural and neurophysiological features of cognitive frailty in relation to healthy aging, and clinical presentations of mild cognitive impairment and Alzheimer’s disease. Cognitive performance of the cognitively frail group was similar to those with mild cognitive impairment. We used a novel cross-modal oddball task to induce mismatch responses to unexpected stimuli. Both controls and cognitively frail showed stronger mismatch responses and larger temporal grey matter volume, compared to people with mild cognitive impairment and Alzheimer’s disease. Our results suggest that cognitively frail represents a spectrum of normal ageing rather than incipient or undiagnosed Alzheimer’s disease. Lower cognitive reserve, hearing impairment and medical comorbidity might contribute to the aetiology of cognitive impairment.