Health-Deficit Accumulation Affects Risk for Mild Cognitive Impairment, Dementia


Frailty index score can identify patients at risk for cognitive dysfunction and might be an important marker with potential prognostic value.

David D. Ward, PhD

Newly published data suggests health-deficit accumulation, specifically among older Americans, affects the likelihood of progressive cognitive impairment, as well as the likelihood of cognitive improvement independent of the APOE ε4 allele.

Lead author David D. Ward, PhD, postdoctoral fellow, geriatric medicine research, Centre for Health Care of the Elderly, Nova Scotia Healthy Authority, and colleagues calculated a frailty index score using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer’s Coordinating Center (NACC). Among those not cognitively impaired (NCI; n = 9773), each 0.1 increment increase in score were associated with a higher risk of developing mild cognitive impairment (MCI) and a higher risk of developing dementia.

In total, there were 14,490 participants in the study with a mean age of 72.2 years. In the MCI subsample (n = 4717) at baseline, there was a higher degree of frailty that was associated with a lower probability of being reclassified as NCI from MCI, a higher risk of returning to MCI in those who were reclassified as NCI, and a higher risk of progressing to dementia.

"We conclude that frailty is a key risk factor for age-related cognitive dysfunction and dementia, representing both a target for interventions aimed at the prevention of age-related cognitive impairment and possible prognostic marker among those who have MCI,” Ward and colleagues noted.

The score is a health-state measure, incorporating information from multiple physiological systems, and closely reflects an individual’s risk for adverse health events and mortality independently of chronological age. A higher frailty index score indicated accumulation of more age-related health deficits while approximating biological age.

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Ward et al. aimed to detail the dynamic nature of cognitive functioning by calculating the likelihood of transitions between cognitive states in both directions over a 12-month period. Decline of cognitive function was considered forward transition, whereas improvement of cognitive functioning was defined as backwards transition.

The investigators also assessed whether frailty index score and APOE ε4 allele carrier status exerted independent or interactive effects on cognitive-state transition probabilities. They found no statistically significant interactions between these variables for any transition in the NCI subsample. However, in the MCI subsample, the association of the frailty index score and the risk of progressing to dementia was significantly weaker in those carrying an APOE ε4 allele than in non-carriers (interaction hazard risk [HR], 0.88; 95% CI, 0.80–0.97).

There were no meaningful differences in these associations when participants whose race was other than white were removed from the analytical sample. Notably, associations of the frailty index score with transition probabilities did not differ significantly between men and women.

Over 12 months, NCI subsample participants maintained their prior state 43,086 times (90.6%) and transitioned between states 4491 times (9.4%), 3086 (68.7%) of which were transitions between cognitive states, with 1405 (31.3%) transitions to death. Of the cognitive-state transitions in the NCI subsample, 80.9% were forward transitions, and 19.1% were backward transitions. In the MCI subsample, 70.5% were forward compared to 29.5% who experienced backwards transition.

"This work supports an emerging conceptualization of late-onset dementia as a complex outcome of aging that often is intimately related to an individual’s general health, as well as genetic risk factors,” Ward et al concluded.

Ward DD, Wallace LM, Rockwood K. Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia. J Neurol Psychiatry. Published online November 13, 2020. doi: 10.1136/jnnp-2020-324081.
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