A new study suggests that patients with few Alzheimer’s disease-related brain changes, such as amyloid deposition, might be at risk of dementia if they have high levels of frailty.
“Frailty could trigger the clinical expression of dementia when it might remain asymptomatic in someone who is not frail”
The researchers suggest that frailty makes older adults more susceptible to Alzheimer’s dementia, and moderates the effects of dementia-related brain changes on dementia symptoms.
As a result, they said their findings suggested that frailty should be considered in clinical care and management of Alzheimer’s dementia.
The findings support the idea that late-life dementia is a complex phenomenon rather than a single disease entity marked by genetic risk or single protein abnormalities in the brain, they noted.
Previous research has shown that some with Alzheimer’s disease-related brain changes can have few characteristic symptoms of the disease, whereas others with few 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, noted the researchers.
In their study, they used modelling to assess relationships between frailty, Alzheimer’s disease-related brain changes, and Alzheimer’s dementia among 456 patients who had either no dementia or Alzheimer’s dementia, and who subsequently died and underwent brain autopsy.
Every year, the study participants received neuropsychological and clinical evaluations, which included detailed cognitive testing and neurological examinations.
Diagnosis of Alzheimer’s dementia was based on clinician consensus, with just over half of the participants given a diagnosis of possible or probable Alzheimer’s dementia at their last assessment.
Brain plaques and tangles were measured after death to quantify Alzheimer’s disease-related changes.
In addition, the researchers developed a frailty index using a combination of 41 factors – including fatigue, joint and heart problems, osteoporosis, mobility and meal preparation.
Overall, 8% of participants had substantial Alzheimer’s disease-related brain changes without having been diagnosed with dementia, and 11% had Alzheimer’s dementia but only little brain changes.
The analysis revealed that frailty and Alzheimer’s disease-related brain changes independently contribute to dementia status, after adjusting for age, sex, and education, said the researchers.
They also found a significant association between frailty and Alzheimer’s disease-related brain changes after excluding activities of daily living from the frailty index and adjusting for other risk factors such as stroke, heart failure, high blood pressure, and diabetes.
“It is possible that helping people to maintain function and independence in later life could reduce both dementia risk”
Lead study author Professor Kenneth Rockwood, from Nova Scotia Health Authority and Dalhousie University, said: “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.
“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,” he said. “This is an enormous step in the right direction for Alzheimer’s research.
“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,” he said.
He added: “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 study, published in The Lancet Neurology journal, was funded by the Canadian Institutes of Health Research, including via the Canadian Collaboration on Neurodegeneration in Aging.