6 healthy lifestyles to avert dementia

Adhering to six healthy lifestyles is tied to slower cognitive decline in older adults regardless of their APOE ε4 allele status in a large, population-based study in China.

“The finding might offer important information to protect older adults against memory decline,” said study author Dr Jianping Jia from the Innovation Center for Neurological Disorders and the Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.

“APOE ε4 is the strongest known risk factor for Alzheimer’s disease and related dementias, and within the context of ongoing and future targeted prevention trials, this outcome is particularly important,” commented Professor Severino Sabia from the Université Paris Cité in Paris, France, and Professor Archana Singh-Manoux from the University College London, London, UK, in an accompanying editorial. “These results support the notion that lifestyle change might counteract the deleterious effect of APOE ε4 on cognitive decline and dementia,” they pointed out. [BMJ 2023;380:p117]

Other than APOE ε4, chronic diseases, and lifestyle patterns can affect memory. However, very few studies have investigated the impact of lifestyle on memory.

Jianping and team investigated the association between healthy behaviours and memory decline in 29,072 individuals 60 years and older who had normal cognitive function at baseline and underwent APOE genotyping when the study began in 2009. They were followed up until death, discontinuation with the trial, or until the trial ended on December 26, 2019. [BMJ 2023;380:e072691]

Mean age of the patients was 72.23 years; 48.54 percent were women. About 20.5 percent were APOE ε4 carriers.

6 healthy behaviours assessed

Six healthy patterns – healthy diet (adherence to the recommended intake of at least seven of 12 eligible food items 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 weekly), active cognitive activity (≥twice weekly), never or previously smoked, and never drank alcohol – were all analysed.

Lifestyle was scored based on the number of healthy factors participants engaged in. The resulting score was categorized as favourable (four to six factors), average (two to three factors), and unfavourable (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, and long delay recall, and long delay 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 behaviour was associated with a slower decline in memory over 10 years. The healthy lifestyle score was associated with a slower memory decline in a dose-response manner.

Memory decline over 10 years in the favourable lifestyle group was 0.28 points slower compared with the group that had unfavourable lifestyles on a standardised score (z score) of the AVLT. Memory decline in the average lifestyle group was 0.16 points slower.

Strongest deterrent to memory decline

A healthy diet, as well as cognitive activity, regular physical exercise, abstaining from alcohol, and not smoking turned out to be significantly linked to slower memory decline despite the presence of APOE ε4. 

“Healthy diet had the strongest protective effect on memory, followed by cognitive activity, and physical exercise,” said the researchers.

Memory decline was faster in APOE ε4 vs non-APOE ε4 carriers (0.002 points per year; p= 0.007). Those with favourable or average lifestyle were almost 90 percent and 30 percent less likely to develop dementia or mild cognitive impairment, relative to those with an unfavourable lifestyle.

During the 10-year study period, 7,164 participants died, and 3,567 stopped participating in the trial.

APOE ε4 tied to impaired memory function

About 25 percent of the general population carry one copy of APOE ε4; 2–3 percent carry two copies, although inheriting APOE ε4 does not mean an individual will get to develop the condition. [https://www.nia.nih.gov/news/study-reveals-how-apoe4-gene-may-increase-risk-dementia]

Whether the effect of the APOE genotype on memory in patients with mild cognitive impairment is impacted by age and underlying AD pathology has been investigated previously. What was found was the presence of the APOE ε4 is associated with impaired memory functioning in both middle-aged and old patients with mild cognitive impairment, although the memory function impacted varies with age. [Dement Geriatr Cogn Disord 2008;26:101-108]

“Memory declines with age, but age-related memory decline is not necessarily a prodrome of dementia,” explained Jianping. “It merely suggests senescent forgetfulness, which can 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. What is unclear is how APOE ε4 perturbs the intracellular lipid state.

One study showed that manipulating lipid metabolism could be one therapeutic approach to alleviate the consequences of carrying the APOE4 allele. [Sci Transl Med 2021;13(583):eaaz4564]

Future directions for research

Sabia and Singh-Manoux said more studies are warranted to identify which key behaviours to target, which combination, the cut-off risk, and when to intervene. With dementia prevention in mind, they said research should identify “not only the factors that matter most but also the threshold at which they matter, and the age when intervention is likely to be most effective.”