Frailty plays a key role in dementia risk
medwireNews: Frailty appears to modify the relationship between Alzheimer’s disease (AD) pathology and Alzheimer’s dementia, with increased levels making people more susceptible to clinical disease.
“That frailty is related to both odds of Alzheimer’s dementia and disease expression has implications for clinical management, since individuals with even a low level of Alzheimer’s disease pathology might be at risk for dementia if they have high amounts of frailty”, say Kenneth Rockwood (Dalhousie University, Halifax, Nova Scotia, Canada) and colleagues.
In a cross-sectional analysis of 456 participants of the Rush Memory and Aging project, frailty measured using the 41-item frailty index and AD pathology quantified from autopsy measure of neurofibrillary tangles and neuritic diffuse plaques both independently predicted Alzheimer’s dementia, increasing the odds 1.76-fold and 4.81-fold, respectively, after accounting for age, sex and education.
Also, the addition of frailty significantly improved the model fit for the relationship between AD pathology and Alzheimer’s dementia and there was a significant interaction between frailty and AD pathology, with an odds ratio of 0.73.
In all, 242 of the study participants were diagnosed with possible or probable Alzheimer’s dementia at their last annual clinical assessment. The remaining patients did not have any form of dementia.
The researchers note in The Lancet Neurology that “for about one person in six, the relationship between Alzheimer’s disease pathology and dementia was weak”, in that 8% of patients had a high burden of AD pathology without being diagnosed with dementia, while 11% had been diagnosed with dementia but had a low burden of AD pathology.
The average frailty index for the whole sample was 0.42 points, based on the number of health deficits present divided by the number of health variables measured. The median was 0.41 points, which is a cutoff point often used to distinguish between moderately and severely frail people, the researchers note.
Patients diagnosed with dementia had a significantly higher frailty index score, on average, than those without dementia, and this was highest among those with a low burden of AD pathology for whom the average score was 0.55 points versus 0.50 and 0.46 points for those with intermediate and high burden, respectively.
Among patients with a low burden of AD pathology, 69% of patients with high frailty had dementia, compared with 5% of patients with low frailty.
Rockwood and co-workers suggest that “[f]railty might reduce the threshold of Alzheimer’s disease pathology needed to cause clinical disease,” and add that “it probably also contributes to other mechanisms in the body that give rise to dementia (eg, inflammation, immunosenescence), weakening the direct link between Alzheimer’s disease pathology and dementia.”
They suggest that “frailty should be used for risk stratification and to guide the management and treatment of older adults and supports the notion that many factors contribute to the development of late-life dementia”.
Commenting on the findings in a related article, Francesco Panza and colleagues, from University of Bari Aldo Moro in Italy, make the point that primary frailty that is not associated with a specific disease may be better defined using a biopsychosocial model rather than the deficit accumulation-based frailty index used by Rockwood and team, which does not completely capture the vulnerability of older adults at risk of developing dementia.
“[T]he biopsychosocial model might add important value in both the assessment and targeting of interventions in patients with frailty; however, at present the model is not fully operationalised”, they say.
By Lucy Piper
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