DOI: 10.1002/alz.079650 ISSN: 1552-5260

Baseline Frailty and Domain‐specific Cognitive Declines in Healthy and MCI Older Adults

Albert C. Liu, Grace Shu Hui Chiang, Michelle C Carlson, Qian‐Li Xue
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Both physical frailty and cognitive decline increase with age and each place adults at elevated risk for loss of independence. Inconsistent associations have been found between frailty and risk for cognitive declines across cognitive domains. However, most studies were cross‐sectional and did not include a comprehensive battery of neuropsychological tests. We hypothesized that frail older adults, whether with or without Mild Cognitive Impairment (MCI) at baseline, are at risk for accelerated domain‐specific cognitive declines.


The Ginkgo Evaluation of Memory Study (GEMS) was a prospective study of 3069 dementia‐free older adults aged 72‐96 years, followed for up to 7.5 years or a diagnosis of dementia, 482 of whom were diagnosed with MCI at baseline. A modified physical frailty phenotype was constructed using GEMS baseline data. A Neuropsychological Battery consisted of 13 tests reflecting global cognition, memory, visual‐spatial construction, language, psychomotor speed/attention, and executive function were administered annually. Linear random effects models were used to compare differences in baseline and rate of change in domain scores among individuals with and without baseline frailty.


Overall, frail participants showed poorer baseline cognitive function in all domains, and greater declines in all cognitive domains. When stratified by baseline MCI, among non‐MCI participants, those with frailty revealed poorer baseline psychomotor speed/attention and executive function, and greater declines in all cognitive domains. Among MCI participants, those with frailty exhibited lower baseline visual‐spatial construction, and greater declines in all cognitive domains except for visual‐spatial construction and executive function. In all cognitive domains, the estimated effect of frailty on cognitive decline was greater in MCI participants than non‐MCI participants.


Frailty was predictive of accelerated cognitive declines across domains and more so in those with baseline MCI. The results from this study highlight the importance of assessing frailty as a risk factor for accelerated cognitive declines, particularly among those at elevated preclinical cognitive risk. These individuals may be at the greatest risk of transitioning to dementia.

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