Clinical Challenges: Lifestyle and Alzheimer’s Risk

Can lifestyle changes reduce Alzheimer’s risk? Ongoing clinical Trials aim to find out.

Major observational studies have linked healthy behavior to lower risk of Alzheimer’s disease. In 2020, research led by Klodian Dhana, MD, PhD, of Rush University School of Medicine in Chicago, showed that people who adhered to four or all five specified healthy behaviors – physical activity, not smoking, light-to-moderate alcohol consumption , high-quality diet, and Cognitive activities – had a 60% lower risk of Alzheimer’s dementia than people who adhered to zero or one factor.

More recently, Dhana and colleagues showed that those same behaviors were associated with a longer life, and importantly, that the extra years did not mean more time living with Alzheimer’s.

“With an increasing number of people affected by Alzheimer’s disease and other dementias, and recognizing the burden of such disease has on public health, we investigated the role of lifestyle factors in dementia risk,” Dhana told MedPage Today.

“Since these lifestyle factors evaluated are relatively modifiable – diet, for example, or physical and cognitive activities – they may impact the future risk of disease,” they said. “However, these studies are observational and lifestyle factors were self-reported, prone to bias.”

US POINTER is an ongoing clinical trial that is evaluating the effect of lifestyle interventions on cognition, Dhana noted. “The results of this clinical trial are needed to validate the findings from observational studies,” he said.

US POINTER

The US POINTER trial is a 2-year study testing whether lifestyle interventions focused on physical exercise, Nutrition, Cognitive challenges, and risk factor management can reduce Cognitive impairment in 2,000 older Americans at risk for sedentary lifestyle, poor diet, and other factors.

POINTER adapted interventions from the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) trial to fit the US culture, noted Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association in Chicago.

FINGER showed that a 2-year combination therapy simultaneously targeting physical exercise, healthy diet, cognitive stimulation, and self-monitoring of cardiac and metabolic risk factors had a protective effect on cognitive function. Performance improved in all Cognitive subdomains, including executive function, processing speed, and complex memory tasks.

“The FINGER study evaluated a very specific lifestyle recipe in individuals thought to be at increased risk in a population in Finland,” Snyder told MedPage Today. “The question was, would this translate in other parts of the world that did not have the same healthcare system in Finland has and that had more diverse populations.”

“This set the stage for the Alzheimer’s Association to launch the US POINTER trial,” she continued. “In a large number of individuals, in a diverse population across the United States, does a very specific risk intervention strategy that combines multiple components of lifestyle have an impact on cognition in people thought to be at increased risk over 2 years?”

“One of the differences is that we don’t have access to the same type of healthcare data and medical records they had in Finland,” Snyder said. “So, we’re really looking at what the science has told us may contribute to the risk.”

POINTER has two interventions: a self-guided and a structured program. The self-guided intervention gives participants education, support, and tools to help them carry out healthier lifestyle practices. The structured intervention gives participants a structured program of diet, physical and cognitive exercise, and cardiometabolic risk management.

The trial includes ancillary studies to identify the effects of lifestyle interventions on specific components of Alzheimer’s, noted Kristina McLinden, PhD, program director at the National Institute on Aging (NIA) in Bethesda, Maryland.

“One of the ancillary studies will look at neuroimaging to see what impact lifestyle modifications have on the brain,” McLinden said in an interview with MedPage Today. This will include amyloid and tau Imaging, as well as assessments of brain shape and size.

“We’ll also look at the effect of these lifestyle interventions on neurovasculature,” she added. “We’ll have the POINTER-zzz study to look at whether lifestyle interventions improve sleep, and we’ll look at the impact of interventions on the microbiome.”

EXERT and MIND

The NIA is supporting other phase III randomized controlled Trials, including the EXERT and MIND studies, to look at specific lifestyle interventions in targeted populations, McLinden noted.

EXERT is studying the effects of exercise for 18 months on cognition, functional status, brain atrophy and blood flow, and cerebrospinal fluid biomarkers of Alzheimer’s disease in humans ages 65 to 89 with amnestic mild Cognitive impairment. MIND is evaluating the Cognitive outcomes of a 3-year intervention of the MIND diet – a hybrid of the Mediterranean and DASH diets – on people ages 65 to 84 without Cognitive impairment who are overweight and have suboptimal diets.

“We’re supporting a microbiome ancillary to the MIND diet study,” McLinden added. “We all have very different gut microbiomes that will respond differently to dietary interventions. This may help us take a precision medicine approach to lifestyle interventions.”

Prevention has a tremendous role to play in Alzheimer’s disease, she said.

“If we can delay the onset of Alzheimer’s disease by a few years, it will obviously have an impact on individual lives, and that is important,” she noted. “It could also have a tremendous impact on health expenditures in this country. You could save billions by having the development of Alzheimer’s disease delayed by even a few years.”

“I also think drug approaches to Alzheimer’s can be further augmented by lifestyle interventions,” McLinden added. “That’s something we’re interested in. Exploring. It could be that drugs are enhanced by lifestyle interventions.”

  • Judy George covers Neurology and Neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, Autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

Dhana has no relationships to disclose.

Snyder is an employee of the Alzheimer’s Association.

McLinden is an employee of the National Institute on Aging.

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