Adherence to six healthy lifestyles is linked to slower cognitive decline in older adults, regardless of their APOE ε4 allele status, in a large study from China.
“This finding could offer important information to protect older adults from memory decline,” said study author Dr. Jianping Jia, of the Center for Neurological Disorders Innovation and the Department of Neurology at the University. Xuan Wu Hospital of Capital Medical University, Beijing, China.
“APOE ε4 is the most important known risk factor for Alzheimer’s disease and related dementias, and in the context of ongoing and future targeted prevention trials, this result is particularly important,” commented Professor Severino Sabia of Paris Cité University in Paris, France, and Professor Archana Singh-Manoux of University College London, London, United Kingdom, in an accompanying editorial. “These results support the idea that lifestyle change could counteract the deleterious effect of APOE ε4 on cognitive decline and dementia,” they noted. (BMJ 2023;380: p117)
In addition to APOE ε4, chronic diseases and lifestyle can affect memory. However, very few studies have investigated the impact of lifestyle on memory.
Jianping and his team studied the association between healthy behaviors and memory decline in 29,072 individuals aged 60 and older who had normal cognitive function at baseline and who underwent APOE genotyping at the start of the study in 2009. They were followed until death, termination of the trial or until the end of the trial on December 26, 2019. (BMJ 2023;380:e072691)
The average age of the patients was 72.23 years; 48.54 percent were women. About 20.5 percent were APOE ε4 carriers.
6 healthy behaviors assessed
Six healthy habits – healthy eating (adhering to the recommended intake of at least seven of the 12 eligible foods such as fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked and never drank alcohol – were all analyzed.
Lifestyle was scored based on the number of healthy factors participants considered. The resulting score was categorized as favorable (four to six factors), average (two to three factors), and unfavorable (zero to one factor).
Memory function was assessed using the World Health Organization/University of California Los Angeles Auditory Verbal Learning Test (AVLT), a composite measure including tests of immediate, short-delay recall and long-term, as well as long-term recognition. Global cognition was assessed using the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory.
The link between lifestyle and cognition
Each individual healthy behavior was associated with slower memory decline over 10 years. Healthy lifestyle score was associated with slower memory decline in a dose-response manner.
The 10-year memory decline in the favorable lifestyle group was 0.28 points slower than that in the unfavorable lifestyle group according to a standardized score (z-score) of the AVLT. Memory decline in the average lifestyle group was 0.16 points slower.
The Strongest Deterrent Against Memory Decline
A healthy diet, along with cognitive activity, regular exercise, abstaining from alcohol, and not smoking were found to be significantly linked to slower memory decline despite the presence of APOE ε4.
“A healthy diet had the strongest protective effect on memory, followed by cognitive activity and physical exercise,” the researchers said.
Memory decline was faster in APOE ε4 than in non-APOE ε4 carriers (0.002 points per year; p= 0.007). People with a favorable or average lifestyle were almost 90 percent and 30 percent less likely to develop dementia or mild cognitive impairment, compared to those with an unfavorable lifestyle.
During the 10-year study period, 7,164 participants died and 3,567 stopped participating in the trial.
APOE ε4 linked to impaired memory function
About 25 percent of the general population has one copy of APOE ε4; 2 to 3 percent carry two copies, although inheriting APOE ε4 does not mean an individual will develop the disease. (https://www.nia.nih.gov/news/study-reveals-how-apoe4-gene-may-increase-risk-dementia)
Whether the effect of APOE genotype on memory in patients with mild cognitive impairment is influenced by age and underlying AD pathology has been previously investigated. What was observed was the presence of APOE ε4
is associated with impaired memory functioning in middle-aged and elderly patients with mild cognitive impairment, although affected memory function varies with age. (Dementia, geriatrics, cognitive disorders 2008;26:101-108)
“Memory declines with age, but age-related memory decline is not necessarily a prodrome of dementia,” Jianping explained. “This simply suggests senescent forgetting, which may be reversed or become stable.”
As APOE is a lipid transport protein. Lipid dysregulation has also recently emerged as a key feature of several neurodegenerative diseases, including Alzheimer’s disease. What is not clear is how APOE ε4 disrupts the intracellular lipid state.
A study showed that manipulation of lipid metabolism could constitute a therapeutic approach to alleviate the consequences of carrying the APOE4 allele. (Sci Transl Med 2021;13(583):eaaz4564)
Future Research Directions
Sabia and Singh-Manoux said additional studies are needed to identify key behaviors to target, what combination, the risk limit and when to intervene. With dementia prevention in mind, they said research should identify “not only the most important factors, but also the threshold at which they matter and the age at which intervention is likely to be most important.” more efficient “.
