Frailty in elderly linked to dementia: Lancet

Illinois, USA: Frailty in older adults may make them more susceptible to Alzheimer's dementia, and moderates the effects of dementia-related brain changes on dementia symptoms, according to a new study.

Findings, published in The Lancet Neurology journal suggests that frailty should be considered in the clinical care and management of Alzheimer's dementia.

Kenneth Rockwood, Nova Scotia Health Authority/Dalhousie University, Halifax, Canada, and colleagues conducted the study to examine whether frailty, which is associated with both age and dementia, moderates the relationship between Alzheimer's disease pathology and Alzheimer's dementia.

In this study, researchers used modeling to assess relationships between frailty, Alzheimer's disease-related brain changes, and Alzheimer's dementia among 456 participants of the Rush Memory and Ageing Project (MAP) who had either no dementia or Alzheimer's dementia, and who subsequently died and underwent brain autopsy. MAP is a longitudinal clinical-pathological study of older adults living in Illinois, USA, which began in 1997.

Every year participants received neuropsychological and clinical evaluations, which included detailed cognitive testing and neurological examinations. Clinical diagnosis of Alzheimer's dementia was based on clinician consensus, with just over half (53%; 242) the participants given a diagnosis of possible or probable Alzheimer's dementia at their last clinical assessment. Brain plaques and tangles were measured after death to quantify Alzheimer's disease-related changes. The researchers also developed a frailty index using a combination of 41 components of health status (eg, fatigue, joint and heart problems, osteoporosis, mobility, meal preparation) obtained at each clinical evaluation.

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Key Findings:

• 242 (53%) had a diagnosis of possible or probable Alzheimer's dementia at their last clinical assessment.


• Frailty and Alzheimer's disease pathology were independently associated with Alzheimer's dementia, after adjusting for age, sex, and education.


• When frailty was added to the model for the relationship between Alzheimer's disease pathology and Alzheimer's dementia, model fit improved.


• There was a significant interaction between frailty and Alzheimer's disease pathology.


• People with an increased frailty score had a weakened direct link between Alzheimer's disease pathology and Alzheimer's dementia; that is, people with a low amount of frailty were better able to tolerate Alzheimer's disease pathology, whereas those with higher amounts of frailty were more likely both to have more Alzheimer's disease pathology and for it to be expressed as dementia.

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"By reducing an individual's physiological reserve, frailty could trigger the clinical expression of dementia when it might remain asymptomatic in someone who is not frail," explains Professor Rockwood. "This indicates that a 'frail brain' might be more susceptible to neurological problems like dementia as it is less able to cope with the pathological burden."

"This is an enormous step in the right direction for Alzheimer's research. Our findings suggest that the expression of dementia symptoms results from several causes, and Alzheimer's disease-related brain changes are likely to be only one factor in a whole cascade of events that lead to clinical symptoms. Understanding how individual risk factors work together to give rise to late-life dementia is likely to offer a new way to develop targeted treatment options."

The findings support the idea that late-life dementia (and particularly Alzheimer's disease) is a complex phenomenon rather than a single disease entity marked by genetic risk or single protein abnormalities in the brain. However, the authors caution that this study is a cross-sectional comparison of pathology data from a single database that only includes adults living in Illinois, USA.

"While frailty is likely to reduce the threshold for Alzheimer's disease-related brain changes to cause cognitive decline, it probably also contributes to other mechanisms in the body that give rise to dementia, weakening the direct link between Alzheimer's disease-related brain changes and dementia," says Rockwood.

"While more research is needed, given that frailty is potentially reversible, it is possible that helping people to maintain function and independence in later life could reduce both dementia risk and the severity of debilitating symptoms common in this disease."

The authors say that future studies should examine longitudinal relationships between frailty, cognition, and biomarkers of Alzheimer's dementia to establish causation.

For further reference log on to https://doi.org/10.1016/S1474-4422(18)30371-5