Frailty could make older people more susceptible to dementia

New research suggests that frailty makes older adults more susceptible to Alzheimer’s dementia, and moderates the effects of dementia-related brain changes on dementia symptoms.

The findings suggest that frailty should be considered in clinical care and management of Alzheimer’s dementia.

The study found that older adults (59 years and older) with higher levels of frailty were more likely to have both Alzheimer’s disease-related brain changes and symptoms of dementia.

But others with substantial brain changes, but who were not frail, showed fewer clinical symptoms.

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.

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 researchers caution that this study is a cross-sectional comparison of pathology data from a single database that only includes adults living in Illinois, USA.

Previous research has shown that some people with Alzheimer’s disease-related brain changes (eg, amyloid deposition) can have few characteristic symptoms of the disease (cognitive and functional decline), but others with few brain changes may have symptoms.

These discrepancies suggest that some hidden factors might affect the relationship between Alzheimer’s disease-related brain changes and Alzheimer’s dementia.

Most people who develop Alzheimer’s dementia are older than 65 years and have several other health problems.

Frailty—a condition linked with reduced physiological reserve and increased vulnerability to other ailments—is associated with age and higher rates of cognitive deficit and dementia, but little research has explored how these conditions might be related.


In this study, the researchers used modelling to assess relationships between frailty, Alzheimer’s disease-related brain changes, and Alzheimer’s dementia among 456 participants who had either no dementia or Alzheimer’s dementia, and who subsequently died and underwent brain autopsy.

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.

The analysis revealed that frailty and Alzheimer’s disease-related brain changes independently contribute to dementia status, after adjusting for age, sex, and education.

The researchers also found a significant association between frailty and Alzheimer’s disease-related brain changes.

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.

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.

They also note several limitations, including that a single definition of frailty has not been well established—some definitions are more biological, others are more physical, whilst some combine physical, biological, psychological, and social risk factors.

The study is published in The Lancet Neurology journal.

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Source: The Lancet Neurology.