Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large, population-based study suggests.
Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.
After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.
"A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele," study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China, write.
"This study might offer important information to protect older adults against memory decline," they add.
The study was published online January 25 in The BMJ.
Preventing Memory Decline
Memory "continuously declines as people age," but age-related memory decline is not necessarily a prodrome of dementia and can "merely be senescent forgetfulness," the investigators note. This can be "reversed or [can] become stable," instead of progressing to a pathologic state.
Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle "receiving increasing attention as a modifiable behavior."
Nevertheless, few studies have focused on the impact of lifestyle on memory; and those that have are mostly cross-sectional and also "did not consider the interaction between a healthy lifestyle and genetic risk," the researchers note.
To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.
The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study's conclusion.
Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.
The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California–Los Angeles Auditory Verbal Learning Test.
"Lifestyle" consisted of six modifiable factors:
Physical exercise (weekly frequency and total time)
Smoking (current, former, or never-smokers)
Alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking)
Diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea)
Cognitive activity (writing, reading, playing cards, mahjong, other games)
Social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online)
Participants' lifestyle was scored on the basis of the number of healthy factors they engaged in.
Participants were also stratified by APOEgenotype into APOE4 carriers and noncarriers.
Demographic and other items of health information, including the presence of medical illness, were used as covariates. The researchers also included the "learning effect of each participant as a covariate, due to repeated cognitive assessments."
Important for Public Health
During the 10-year period, 7164 participants died, and 3567 stopped participating.
Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005 – 0.009], P < .001; and 0.002 [0 .000 – 0.003], P = .033 points higher, respectively), compared to those in the unfavorable group.
Healthy diet had the strongest protective effect on memory.
Memory decline occurred faster in APOE4 vs non-APOE4 carriers (0.002 points/year [95% CI, 0.001 – 0.003]; P = .007).
But APOE4 carriers with favorable and average lifestyles showed slower memory decline (0.027 [0.023 – 0.031] and 0.014 [0.010 – 0.019], respectively), compared to those with unfavorable lifestyles. Similar findings were obtained in non-APOE4 carriers.
Those with favorable or average lifestyle were respectively almost 90% and 30% less likely to develop dementia or MCI, compared to those with an unfavorable lifestyle.
The authors acknowledge the study's limitations, including its observational design and the potential for measurement errors, owing to self-reporting of lifestyle factors. Additionally, some participants did not return for follow-up evaluations, leading to potential selection bias.
Nevertheless, the findings "might offer important information for public health to protect older against memory decline," they note — especially since the study "provides evidence that these effects also include individuals with the APOE4 allele."
"Important, Encouraging" Research
Commenting for Medscape Medical News, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings "important and encouraging."
However, said Sabia, who was not involved with the study, "there remain important research questions that need to be investigated in order to identify key behaviors, which combination, the cutoff of risk, and when to intervene."
Future research on prevention "should examine a wider range of possible risk factors" and should also "identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one."
In an accompanying editorial, Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.
They liken it to the "multifactorial risk paradigm introduced by the Framingham study," which has "led to a substantial reduction in cardiovascular disease." A similar approach could be used with dementia prevention, they suggest.
The study was funded by the Key Project of the National Natural Science Foundation of China; the National Key Scientific Instrument and Equipment Development Project; the Key Project of the National Natural Science Foundation of China; the Beijing Scholars Program; the Beijing Brain Initiative from the Beijing Municipal Science and Technology Commission; the CHINACANADA Joint Initiative on Alzheimer's Disease and Related Disorders; the Mission Program of Beijing Municipal Administration of Hospitals; National Natural Science Foundation of China; the National Science and Technology Foundation of China; the Beijing Natural Science Foundation; Major Project of Beijing Municipal Science and Technology Commission; and the Sailing Plan of Beijing Municipal Administration of Hospitals. The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Sabia received grant funding from the French National Research Agency. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.
BMJ. Published online January 25, 2023. Full text, Editorial
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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Lynch syndrome is a genetic disease which predisposes individuals to a variety of cutaneous and internal malignancies. Cutaneous tumours associated with Lynch syndrome include sebaceous neoplasms and keratoacanthomas. Lynch syndrome is due to a mutation in one of several genes that are responsible for DNA mismatch repair. These genes include MLH1, MLH2, MSH6, and PMS2.
This 20-year, retrospective study from Dana-Farber looks at rates and risk factors for developing a Lynch-associated skin neoplasm, as well as non–Lynch-associated skin neoplasms, including basal cell and squamous cell carcinoma in adults with germline mutations in Lynch syndrome–associated genes.
Overall, 21.1% of patients in the study had a documented history of a skin cancer. Among all individuals, 9.2% developed a Lynch syndrome–associated cancer and 15.0% develop a skin cancer that is not classically associated with Lynch syndrome. The most common skin cancer in the cohort was basal cell carcinoma (9.9%), followed by sebaceous adenoma (7.2%). In a multivariate regression analysis, factors associated with a greater likelihood of developing a Lynch-associated skin cancer included MLH1 (aOR, 6.67; P < .001) or MSH2 (aOR, 15.33; P < .001) germline mutations.
Limitations of the study include the single-site nature of the case review; however, the number of cases and granularity of patient demographics is impressive. Overall, dermatologists should be aware that Lynch patients are at an increased risk of skin cancer; however, in this cohort, only around 20% developed at least one. The significance is that not all Lynch syndrome patients are destined to develop skin cancer, and, even if they do, it appears that basal cell carcinoma is more common than sebaceous neoplasms. Still, routine screening of these patients is important because they display higher rates of skin cancer than the general population.
Abstract
BACKGROUND
Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS).
OBJECTIVE
Identify clinical factors associated with development of skin neoplasms in LS.
METHODS
Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020. Multivariable logistic regression was performed to evaluate clinical factors associated with skin neoplasia.
RESULTS
Of 607 LS carriers, 9.2% had LS-associated skin neoplasia and 15.0% had non-LS-associated skin neoplasia; 58.2% (353/607) had documentation of prior dermatologic evaluation; 29.7% (38/128) with skin neoplasms lacked a history of visceral LS-associated malignancy. LS-associated skin neoplasms were significantly associated with male sex, age, race, MLH1 pathogenic germline variants, MSH2/EPCAM pathogenic germline variants, and personal history of non-LS skin neoplasms. Non-LS-associated skin neoplasms was significantly associated with age, number of first- and second-degree relatives with non-LS-associated skin neoplasms, and personal history of LS-associated skin neoplasms.
LIMITATIONS
Single-institution observational study; demographic homogeneity.
CONCLUSIONS
Skin neoplasms are common in individuals with LS. We identified clinical factors associated with LS- and non-LS-associated skin neoplasms. Regular dermatologic surveillance should be considered for all LS carriers.
Journal of the American Academy of Dermatology
Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort
J Am Acad Dermatol 2023 Feb 08;[EPub Ahead of Print], CS Zhong, M Horiguchi, H Uno, C Ukaegbu, A Chittenden, NR LeBoeuf, S Syngal, VE Nambudiri, MB Yurgelun