Lifestyle Interventions Provide Maximum Memory Benefit When Combined; And May Offset Elevated Alzheimer's Risk Due To Genetics, Pollution

FROM THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONFERENCE 2019

LOS ANGELES,July 15,2019 --New research reported at the Alzheimer's Association International Conference(AAIC) 2019 in Los Angeles suggests healthy lifestyle choices — including healthy diet,exercise,and cognitive stimulation — may decrease risk of cognitive decline and dementia. Researchers also found lifestyle modifications may reduce risk even in the face of other risk factors,including genetics and pollution,and provide maximum memory benefit when combined.

Five research studies reported at AAIC 2019 suggest:

Adopting four or five healthy lifestyle factors reduced risk of Alzheimer's dementia by 60% compared to adopting none or only one factor.

Adherence to a healthy lifestyle may counteract genetic risk for Alzheimer's disease.

Having a higher cognitive reserve,built through formal education and cognitive stimulation,may benefit the aging brain by reducing risk of dementia among people exposed to high levels of air pollution.

Confirmation that early adult to mid-life smoking may be associated with cognitive impairment at mid-life,as early as one's 40s.

Alcohol use disorder significantly increased risk of dementia in older women.

"While there is no proven cure or treatment for Alzheimer's,a large body of research now strongly suggests that combining healthy habitspromotes good brain health and reduces your risk of cognitive decline," said Maria C. Carrillo,PhD,Alzheimer's Association chief science officer. "The research reported today at AAIC gives us attainable,actionable recommendations that can help us all live a healthier life."

To determine whether multi-component lifestyle changes can protect memory and thinking skills in people at risk of developing dementia the Alzheimer's Association is leading the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk(U.S. POINTER). U.S. POINTER is the first study to examine these combined interventions in a large-scale,diverse,U.S.-based population. The interventions include physical exercise,nutritional counseling and modification,cognitive and social stimulation,and improved self-management of health. The study is taking place at five sites across the U.S.; initial results are expected in 2023.

Adopting Multiple Healthy Lifestyle Factors May Reduce Risk for Dementia

Growing research suggests adopting several healthy lifestyle factors provides maximum benefit for brain and body health. Using data from the Chicago Health and Aging Project (CHAP; n=1,431) and the Rush Memory and Aging Project (MAP; n=920),Klodian Dhana,MD,assistant professor at Rush University Medical Center in Chicago and colleagues examined how healthy lifestyle mitigates the risk of Alzheimer's disease. The researchers focused on five low-risk lifestyle factors: healthy diet,at least 150 minutes/week of moderate to vigorous physical activity,not smoking,light to moderate alcohol intake,and engaging in cognitively stimulating activities.

During an average follow-up of nine years in CHAP and six years in MAP,there were 293 (21%) and 229 (25%) cases of Alzheimer's dementia,respectively. For study participants who adopted four or five low-risk lifestyle factors,researchers found about 60% lower risk of Alzheimer's dementia when compared with participants who did not follow any or only one of the low-risk factors. The researchers found that for participants who adopted one more low-risk lifestyle factor,whatever their current number of factors,their risk of Alzheimer's dementia decreased by an additional 22%.

"This study highlights the importance of following multiple healthy lifestyle practices for lowering the risk of Alzheimer's dementia," said Dhana. "In the U.S.,adherence to a healthy lifestyle is low,and therefore promoting these lifestyle factors should become the primary goal for public health policies."

Healthy Lifestyle may Counteract Genetic Risk for Dementia

Genetic factors are known to increase risk of Alzheimer's disease,but whether or not this risk can be counteracted by healthy lifestyle is unknown. Using data from 196,383 adults of European ancestry aged 60 and older from UK Biobank,Elżbieta Kuźma,a research fellow at the University of Exeter Medical School,and team,identified 1,769 cases of dementia over a median follow-up period of eight years. The researchers grouped the participants into those with high,intermediate and low genetic risk for dementia,and favorable,intermediate and unfavorable lifestyle based on their diet,physical activity,smoking and alcohol consumption.

To assess genetic risk,the researchers used a polygenic risk score (PRS) based on previously publishedAlzheimer's disease genome-wide association studies statistics,including all mutations associated with Alzheimer's disease. Each genetic risk factor was weighted according to the strength of its association with Alzheimer's. For lifestyle status,the researchers considered no current smoking,regular physical activity,healthy diet and moderate alcohol consumption as healthy behaviors.

The research team found participants with high genetic risk and an unfavorable lifestyle were almost three times more likely to develop dementia compared to those with a low genetic risk and favorable lifestyle (hazard ratio [HR]=2.83,95%; confidence interval [CI]=2.09-3.83,p<0.001). The risk of all-cause dementia was 32% lower among participants with a high genetic risk following a favorable lifestyle compared with an unfavorable lifestyle (HR=0.68; 95% CI=0.51-0.90,p=0.008). Genetic factors were not found to significantly modify the relationship between the healthy lifestyle and dementia risk.

"This research is exciting in that it shows there are actionable things we can do to try to counteract genetic risk for dementia," said Kuźma. "In our study,adherence to a healthy lifestyle was associated with a reduced risk of dementia regardless of the genetic risk."

Cognitive Reserve May Protect Against brain Damage Caused by Air Pollution

Previous research suggests living in locations with high levels of outdoor air pollution — especially tiny particles or droplets in the air known as fine particulate matter — is associated with higher likelihood of Alzheimer's or other dementias,and can cause brain damage and brain shrinkage. Research has also shown that brain damage caused by Alzheimer's does not result in the same degree of cognitive impairment in all persons living with the disease. This may be explained by "cognitive reserve," which is the brain's capacity to cope with the negative impact of brain damage on cognition.

In this new research reported at AAIC 2019,Diana Younan,MPH,a senior research associate at the University of Southern California,and colleagues looked at a population of women aged 65 to 79 years from the Women's Health Initiative Memory Study (n=6,113) who did not have dementia at the time of enrollment to see whether cognitive reserve affects the relationship between exposure to outdoor air pollution and risk of Alzheimer's. Study participants — who were grouped into low or high cognitive reserve based on cognitive functioning scores,years of education,job status and physical activity — were followed over 14 years and tested annually for dementia. The researchers used mathematical modeling to estimate the outdoor air pollution levels at each participant's home.

The study confirmed that living in locations with high air pollution increased the risk for Alzheimer's and other dementias. Importantly,older women with higher cognitive reserve only showed a 21% increased risk due to living in polluted locations compared with a 113% increased environmental risk for those with lower cognitive reserve.

"Our study showed that engaging in physically and mentally stimulating activities is an important element of cognitive reserve,and the resulting benefit may offer protection against brain damage caused by outdoor air pollution exposure in late life," said Younan.

Cigarette Smoking May Reduce Cognitive Function as Early as in Mid-life

Smoking may be a risk factor for cognitive aging,but few studies have looked at how smoking trajectories over the life course are linked to later cognitive function. In new research by Amber Bahorik,MSW,a postdoctoral researcher at the University of California,San Francisco,and team led by Kristine Yaffe,the study's principal investigator,the smoking trajectories of adults from the Coronary Artery Risk Development in Young Adults study (n=3,364; mean age 50.1±3.6) were examined over 25 years to determine their link with cognitive function.

The researchers found that,compared to non-smokers,"heavy stable" smokers were 1.5 to 2.2 times more likely to have cognitive impairment,while "quitters" and "minimal stable" smokers did not have an increased risk. They also found cumulative smoking exposure in people who smoked a pack a day for more than 10 years was associated with poor cognitive function. Cognitive impairment was observed among smokers as early as their 40s.

"Our findings demonstrate that early adult to mid-life smoking may be associated with cognitive impairment much earlier than we expected," said Bahorik. "This adds to the already dense body of evidence showing continued smoking negatively impacts several health functions and emphasizes the benefits of quitting."

Alcohol Use Disorder in Female Veterans Increases Risk for Dementia

Alcohol use disorder (AUD) is the most common substance use disorder among military personnel and is a growing epidemic in women,according to the Committee on Prevention,Diagnosis,Treatment,and Management of Substance Use Disorders in the U.S. Armed Forces. AUD,which is characterized by the National Institutes of Health (NIH) as compulsive alcohol use,loss of control over alcohol intake,and withdrawal when not using,is experienced by an estimated 16 million Americans. A team again featuring Drs. Bahorik and Yaffe from University of California,San Francisco studied how AUD may increase risk of dementia in female veterans.

The researchers studied 2,207 female veterans with AUD and 2,207 female veterans without AUD over the age of 55 at Veterans Health Administration medical centers from October 2004 to September 2015; all women were free from dementia at baseline. During an average of 3.6 years of follow up,4% of female veterans with AUD developed dementia compared to 1% without AUD. After adjustment for demographics,psychiatric conditions and medical comorbidities,women with AUD had a more than threefold increase in risk of developing dementia compared to women without AUD.

"This study highlights the need to consider alcohol use,especially alcohol use disorder,when evaluating dementia risk profiles," said Bahorik. "It also emphasizes the need for programs and services to address the growing problems of both AUD and dementia in older women."

About AAIC

The Alzheimer's Association International Conference (AAIC) is the world's largest gathering of researchers from around the world focused on Alzheimer's and other dementias. As a part of the Alzheimer's Association's research program,AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital,collegial research community.

AAIC 2019 home page:www.alz.org/aaic/

AAIC 2019 newsroom:www.alz.org/aaic/pressroom.asp

About the Alzheimer's Association®

The Alzheimer's Association is the leading voluntary health organization in Alzheimer's care,support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research,to provide and enhance care and support for all affected,and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit alz.orgor call 800.272.3900.

Klodian Dhana,et al. Impact of Healthy Lifestyle Factors on the Risk of Alzheimer's Dementia; Findings from Two Prospective Cohort Studies. (Funded by the National Institute on Aging)

Elzbieta Kuzma,et al. Genetic Risk,Lifestyle and Dementia. (Funder(s): James Tudor Foundation; Mary Kinross Charitable Trust; Halpin Trust; National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care for the South West Peninsula (PenCLAHRC); National Health and Medical Research Council,Australia; National Institute on Aging/National Institutes of Health (NIA/NIH); Alan Turing Institute under the Engineering and Physical Sciences Research Council (EPSRC))

Diana Younan,et al. Heterogeneity in the Increased Risk for Alzheimer's Disease and Related Dementias Associated with Fine Particle Exposure: Exploring the Role of Cognitive Reserve. (Funded by the National Institute of Environmental Health Sciences with data generated by a grant from the National Institute on Aging)

Amber Bahorik,et al. Early Adult to Mid-Life Cigarette Smoking and Cognitive Function: Findings from the Cardia Study. (Funder: U.S. National Institutes of Health)

Amber Bahorik,et al. Alcohol Use Disorders in Female Veterans and the Impact on Dementia Risk. (Funder: U.S. Department of Defense)

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