Alzheimer’s: Healthy lifestyle linked to slower memory decline, regardless of genetic risk

The researchers recruited 29,072 study participants from North, South, and West China aged 60 or older with typical cognitive functions. Their mean age was 72.2 years, and 51.5% were men.

Genetic testing at baseline showed that 20.43% of the study participants were carriers of the APOE ε4 gene, the strongest known risk factor for Alzheimer’s disease and related dementias.

The researchers followed up with the participants at intervals over the next 10 years, in 2012, 2014, 2016, and 2019.

At baseline and each follow-up, the researchers assessed the participants’ memory using the Auditory Verbal Learning Test (AVLT), which includes measurement of immediate recall, short delay-free recall (3 min later), long delay-free recall (30 min later), and long delay recognition.

For this study, Dr. Jia and colleagues used American guidelines and the findings of previous studies to define a healthy lifestyle. They identified six factors:

• a healthy diet – adherence to the recommended intake of at least 7 of 12 eligible food items (fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, and tea)
• regular physical exercise – at least 150 minutes of moderate-intensity activity or at least 75 minutes of vigorous-intensity activity per week
• Active social contact (participation in meetings or attending parties, visiting friends or relatives, traveling, and chatting online) – at least twice per week
• active cognitive activity (writing, reading, playing cards, mahjong, and other games) – at least twice per week
• never smokes (participants who had smoked less than 100 cigarettes in their lifetime) or used to smoke (participants who had quit smoking at least 3 years before the study)
• never drank alcohol or drank occasionally

Researchers categorized participants into groups depending on their number of healthy lifestyle factors:

• 0-1 healthy lifestyle factors = unfavorable lifestyle (6967 participants)
• 2-3 healthy lifestyle factors = average lifestyle (16,549 participants)
• 4-6 healthy lifestyle factors = favorable lifestyle (5556 participants)

All participants’ mean memory test scores declined continuously over the decade, consistent with how memory declines with age. However, the highest memory test scores were observed in the favorable lifestyle group and the lowest in the unfavorable lifestyle group, indicating that participants with favorable lifestyles had slower memory decline than those with unfavorable lifestyles (by 0.028 points/year).

The results showed that a healthy diet had the strongest effect on memory, followed by an active cognitive activity, regular physical exercise, active social contact, never or former smoking, and never drinking.

This study did not identify the mechanisms responsible for modifying memory loss. However, the researchers hypothesized that they might include “reduced cerebrovascular risk, enhancement of cognitive reserve, inhibition of oxidative stress and inflammation, and promotion of neurotrophic factors.”

Dr. Caselli told MNT that the “findings echo heart healthy behaviors (diet, exercise, no smoking in particular), with the addition of active social and cognitive activity, [and] cardiovascular health […] in turn is important for our cognitive health, so whether directly or indirectly [beneficial to memory], these findings seem credible and consistent with other well conducted studies.”

Dorly J.H. Deeg, Ph.D., professor of epidemiology of aging at Amsterdam University Medical Center, who was not involved in the study, also praised the study for its large and varied sample population and the numerous analyses supporting the findings.

The APOE ε4 allele, present in 20.43% of the study participants, is correlated with earlier and more rapidly progressive memory decline and represents a major risk factor for Alzheimer’s disease.

In this study, the researchers observed that a healthy lifestyle positively affected memory in all participants, regardless of whether they carried the APOE ε4 allele or not.

“[W]e find there are some people who are disheartened by finding they are an ε4 carrier […] The findings of this study will hopefully give such people hope that they can actively mitigate their genetically based vulnerability,” said Dr. Caselli.

In their paper, Dr. Jia and colleagues identify several study limitations, including that lifestyle factors were self-reported and thus prone to measurement errors. Furthermore, memory was evaluated using a single neuropsychological test. They also acknowledge the study design did not assess if a healthy lifestyle started affecting memory before the age of 60.

Dr. Caselli told MNT that the possibility that some participants were in the preclinical stage of Alzheimer’s disease cannot be excluded. “Though this entailed a 10-year follow-up, the preclinical phase of Alzheimer’s disease is closer to 20 years so things like social and cognitive activity may already start to decline in subtle ways before a person with preclinical stage disease develops overt symptoms and is diagnosed with MCI [mild cognitive impairment],” he said.

In comments to MNT, Dr. Deeg pointed out that the researchers “excluded a huge number of participants (30% of eligible persons).” In the study paper, “[t]his is described as ‘younger than 60 years, refused to participate, etc’. As a reviewer, I would not think this is a satisfactory explanation,” she said.

Dr. Deeg told MNT that the findings of observational studies such as this one “should be replicated in randomized controlled trials.”

“Such trials have been performed – usually with only one lifestyle factor, mostly physical activity. Unfortunately, the findings are not unequivocal, and a recent JAMA article showed no effects,” she added. “So, we have some way to go to find out what intervention would work, and why – and for this, we need to know what the underlying mechanisms in the brain are.”

In an editorial linked to this study, Séverine Sabia, Ph.D., research professor at Université Paris Cité in France, and Archana Singh-Manoux, Ph.D., research professor at University College London recommend that future research focuses on “identifying 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.”