Frailty could make people more susceptible to develop the risk of Alzheimer's dementia

New research indicates that frailty makes older adults more prone to dementia and Alzheimer's disease, and moderates the effects of dementia-related brain changes on symptoms of dementia.
Alzheimer's disease
High levels of frailty may develop Alzheimer's dementia

Frailty could make people more susceptible to develop the risk of Alzheimer's dementia

More recently, a study report has been published in the journal“The Lancet Neurology” that is referred to show the relationship between frailty and dementia risks or Alzheimer's disease biomarkers.

The research report suggests that high levels of frailty may develop the symptoms and risks of dementia. 

Older adults with physical fragility are more susceptible to develop Alzheimer's dementia and more likely to have brain changes associated with Alzheimer's disease. 

Physical fragility or frailty is a condition which is linked to reduced physiological or low physical reserve and increased vulnerability to other diseases.
It is also related to age, higher rates of dementia and cognitive deficits, but lately, small research has discovered how these conditions can be related. 

The physical fragility or frailty should be considered in the management of Alzheimer's dementia and clinical care.

High levels of frailty may develop Alzheimer's dementia

In the study, researchers have found that frailty makes older people (59 years and older) more susceptible to have Alzheimer's disease-related brain changes on dementia symptoms, while others with significant brain changes, but who were not frail, have fewer clinical signs and symptoms.

Lead author, Kenneth Rockwood, a professor at Nova Scotia Health Authority and Dalhousie University, Canada, explained key points of the study report in his statement and said
“By limiting the physiological reserve of the individual, frailty can lead to a clinical expression of dementia when it may remain non-accidental or asymptomatic in a person who is not frail.
This suggests that a 'frail brain' may be more prone to neurological problems such as dementia because it is less able to handle the disease burden.
This is a huge step in Alzheimer's research in the right direction.
Our findings indicate that the symptoms of dementia are caused by several factors, and brain changes associated with Alzheimer's disease are likely to be only one factor in a whole series of events that cause clinical symptoms.
Understanding and remembering how an individual's risk factors work together to elicit late-life dementia and are more likely to provide a new technique to develop targeted treatment options”.

The conclusions of the study support that the late-life dementia is a complex phenomenon (especially in the case of Alzheimer's disease) rather than a single pathogen or genetic risk or a single protein defect in the brain.
However, the authors have warned that the study is a cross-sectional comparison of pathology data from a single database of adults living in Illinois, USA.

In the previous research, it had been shown that some people with brain changes associated with Alzheimer's disease (such as an amyloid deposition) may have few distinct symptoms of the disease (functional and cognitive decline), while others with few brain changes may have symptoms of dementia.

This discrepancy reveals that some hidden factors may affect the relationship between brain changes associated with Alzheimer's disease and Alzheimer's dementia.

Most people, who develop Alzheimer's dementia and have many other health problems, are more than 65 years old.

In this research, the researchers used modeling to assess the relationships between Alzheimer's dementia, Alzheimer's disease-related brain changes and frailty (vulnerability) among 456 participants of the Rush Memory and Ageing Project (MAP) who died and underwent brain autopsy or brain dissection and who had either no dementia or Alzheimer's dementia.

Memory and Ageing Project (MAP) is a longitudinal clinical-pathological study initiated in 1997 for older people living in Illinois, USA. 

Every year, participants received neurological assessments and clinical evaluations, including detailed neurological examinations and cognitive tests. 

The clinical diagnosis of Alzheimer's disease was based on the consensus of physicians, with just over half (53 percent; 242) giving participants a diagnosis of possible Alzheimer's disease in the recent clinical evaluation.

Brain plaques, aggregates, and tangles were measured after death to determine changes related to Alzheimer's disease. Researchers also developed a frailty index and discovered a brittle index using a combination of 41 components of the health status (for example, stress, joint and heart problems, fatigue, osteoporosis, meal preparation, and mobility) obtained in each clinical evaluation.

Altogether, there was considerable change in the brain related to Alzheimer's disease. Overall, 8% of participants (35 people) had significant Alzheimer's disease-related brain changes without being diagnosed with dementia, and 11 %( 50 people) had Alzheimer's dementia but had few brain changes associated with the disease.

The analysis showed that Alzheimer's disease-related brain changes and frailty independently contribute in the case of dementia, after adjusting for sex, age and education. 

Researchers have also found an important link between frailty and brain changes related to Alzheimer's disease, after excluding daily activities from the frailty index and adjusting for other risk factors such as heart failure, stroke, diabetes, and high blood pressure. 

While frailty is likely to contribute to other mechanisms in the body that lead to dementia, it probably also reduces the threshold of brain changes associated with Alzheimer's disease to cause cognitive decline, weakening the direct link between dementia and brain changes related to Alzheimer's disease.

Whereas more research is needed since frailty can be reversed, it is possible that by helping people to maintain work and independence in later life, the severity of debilitating symptoms and dementia risk both can usually be reduced in this disease”, says Rockwood.

Dr. Francesco Panza from the University of Bari Aldo Moro, Italy, commented how understanding frailty can help indicate and prevent dementia, "In light of current knowledge on Alzheimer's dementia and cognitive frailty phenotype, secondary preventive strategies for physical frailty and cognitive impairment may be suggested.

For example, personalized multimedia or individualized multi-domain interventions can target nutritional, physical, psychological and cognitive domains, which can delay the progression to overt dementia and secondary events of adverse health-related consequences such as hospitalization, mortality, and disability.

In this research, the authors of the study said future studies should examine the longitudinal relationships between vulnerability,  frailty and cognition and the vital signs of Alzheimer's disease to determine the causal relationship.
They noted many limitations, including that not even a single definition of frailty has been established well - some definitions are more physical, others are more biological, while some biological, physical, social and psychological risks factors can be combined.
They also noticed that the frailty measurement was taken closer to death and could reflect the terminal decline, resulting in the relationship between dementia status and Alzheimer's disease-related brain changes among people with high levels of physical fragility and frailty.

Journal Reference: The Lancet Neurology, 2019 DOI: 10.1016/S1474-4422(18)30371-5
Story Source: ScienceDaily, January 2019. Frailty could make people more susceptible to dementia

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