Tag: Older

Healthy Lifestyle Linked to Slower Memory Decline in Older Adults

Brain Connections Neural Network

The researchers uncovered that each personal wholesome habits (healthful eating plan, standard workout, energetic social get in touch with, cognitive action, non-using tobacco, and by no means drinking alcohol) was associated with a slower-than-typical drop in memory in excess of 10 decades just after accounting for other health, economic, and social aspects. The strongest result on slowing memory decrease was a balanced diet, followed by cognitive exercise and then physical work out.

Even individuals with genes connected to Alzheimer’s ailment see advantages.

In accordance to a 10 years-extended review of older grown ups in China, just lately released in The BMJ, a nutritious way of life, specially a nutritious diet plan, is joined to slower memory decrease.

The analyze uncovered that even carriers of the apolipoprotein E (APOE) gene, which is the strongest acknowledged possibility variable for

Memory continuously declines as people age, but evidence from existing studies is insufficient to assess the effect of a healthy lifestyle on memory in later life. And given the many possible causes of memory decline, a combination of healthy behaviors might be needed for an optimal effect.

To explore this further, researchers analyzed data from 29,000 adults aged at least 60 years (average age 72; 49{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} women) with normal cognitive function who were part of the China Cognition and Aging Study.

At the start of the study in 2009, memory function was measured using the Auditory Verbal Learning test (AVLT) and participants were tested for the APOE gene (20{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} were found to be carriers). Follow-up assessments were then conducted over the next 10 years in 2012, 2014, 2016, and 2019.

A healthy lifestyle score combining six factors was then calculated: healthy diet, regular exercise, active social contact (eg. seeing friends and family), cognitive activity (eg. writing, reading, playing mahjong), non-smoking, and never drinking alcohol.

Based on their score, ranging from 0 to 6, participants were put into favorable (4 to 6 healthy factors), average (2 to 3 healthy factors), or unfavorable (0 to 1 healthy factors) lifestyle groups and into APOE carrier and non-carrier groups.

After accounting for a range of other health, economic and social factors, the researchers found that each individual healthy behavior was associated with a slower-than-average decline in memory over 10 years. A healthy diet had the strongest effect on slowing memory decline, followed by cognitive activity and then physical exercise.

Compared with the group that had unfavorable lifestyles, memory decline in the favorable lifestyle group was 0.28 points slower over 10 years based on a standardized score (z score) of the AVLT, and memory decline in the average lifestyle group was 0.16 points slower. Participants with the APOE gene with favorable and average lifestyles also experienced a slower rate of memory decline than those with an unfavorable lifestyle (0.027 and 0.014 points per year slower, respectively).

What’s more, those with favorable or average lifestyles were almost 90{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} and almost 30{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} less likely to develop dementia or mild cognitive impairment relative to those with an unfavorable lifestyle, and the APOE group had similar results.

This is an observational study so can’t establish cause and the researchers acknowledge some limitations, such as the potential for measurement errors due to self-reporting of lifestyle factors, and the possibility of selection bias, as some participants did not return for follow-up evaluations. But this was a large study with a long follow-up period, allowing for the evaluation of individual lifestyle factors on memory function over time. And findings remained significant after further analyses, suggesting that they are robust.

As such, the researchers say their results provide strong evidence that adherence to a healthy lifestyle with a combination of positive behaviors is associated with a slower rate of memory decline, even for people who are genetically susceptible to memory decline. They suggest further research could focus on the effects of a healthy lifestyle on memory decline across the lifespan, acknowledging that memory problems can also affect younger people, not included in this study. “These results might offer important information for public health initiatives to protect older adults against memory decline,” they conclude.

“Prevention is important, given the absence of effective treatments for Alzheimer’s disease and related dementias,” say researchers in a linked editorial.

However, they point out that these results do not help to determine which among the six health behaviors included in the score (or specific combination) is the best target for dementia prevention, or when in the life course to focus prevention efforts. Further insight is also needed to determine whether the differences in memory decline observed in this study are clinically meaningful, they add.

They suggest a similar approach that led to a substantial reduction in cardiovascular disease should be taken with dementia prevention, “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.”

Reference: “Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study” by Jianping Jia, Tan Zhao, Zhaojun Liu, Yumei Liang, Fangyu Li, Yan Li, Wenying Liu, Fang Li, Shengliang Shi, Chunkui Zhou, Heyun Yang, Zhengluan Liao, Yang Li, Huiying Zhao, Jintao Zhang, Kunnan Zhang, Minchen Kan, Shanshan Yang, Hao Li, Zhongling Liu, Rong Ma, Jihui Lv, Yue Wang, Xin Yan, Furu Liang, Xiaoling Yuan, Jinbiao Zhang, Serge Gauthier and Jeffrey Cummings, 25 January 2023, The BMJ.
DOI: 10.1136/bmj-2022-072691

The study was funded by the National Natural Science Foundation of China.

Social frailty comes with health risks for older adults



CNN
 — 

Consider three hypothetical women in their mid-70s, all living alone in identical economic circumstances with the same array of ailments: diabetes, arthritis and high blood pressure.

Ms. Green stays home most of the time and sometimes goes a week without seeing people. But she’s in frequent touch by phone with friends and relatives, and she takes a virtual class with a discussion group from a nearby college.

Ms. Smith also stays home but rarely talks to anyone. She has lost contact with friends, stopped going to church and spends most of her time watching TV.

Ms. Johnson has a wide circle of friends and a busy schedule. She walks with neighbors regularly, volunteers at a local school twice a week, goes to church and is in close touch with her children, who don’t live nearby.

Three sets of social circumstances, three levels of risk should the women experience a fall, bout of pneumonia or serious deterioration in health.

Of the women, Ms. Johnson would be most likely to get a ride to the doctor or a visit in the hospital, experts suggest. Several people may check on Ms. Green and arrange assistance while she recovers.

But Ms. Smith would be unlikely to get much help and more likely than the others to fare poorly if her health became challenged. She’s what some experts would call “socially vulnerable” or “socially frail.”

Social frailty is a corollary to physical frailty, a set of vulnerabilities (including weakness, exhaustion, unintentional weight loss, slowness and low physical activity) shown to increase the risk of falls, disability, hospitalization, poor surgical outcomes, admission to a nursing home and earlier death in older adults.

Essentially, people who are physically frail have less physiological strength and a reduced biological ability to bounce back from illness or injury.

Those who are socially frail similarly have fewer resources to draw upon but for different reasons — they don’t have close relationships, can’t rely on others for help, aren’t active in community groups or religious organizations, or live in neighborhoods that feel unsafe, among other circumstances. Also, social frailty can entail feeling a lack of control over one’s life or being devalued by others.

Many of these factors have been linked to poor health outcomes in later life, along with so-called social determinants of health — low socioeconomic status, poor nutrition, insecure housing and inaccessible transportation.

Social frailty assumes that each factor contributes to an older person’s vulnerability and that they interact with and build upon each other.

“It’s a more complete picture of older adults’ circumstances than any one factor alone,” said Dr. Melissa Andrew, a professor of geriatric medicine at Dalhousie University in Halifax, Nova Scotia, who published one of the first social vulnerability indices for older adults in 2008.

This way of thinking about older adults’ social lives, and how they influence health outcomes, is getting new attention from experts in the United States and elsewhere. In February, researchers at Massachusetts General Hospital and the University of California, San Francisco published a 10-item “social frailty index” in the Proceedings of the National Academy of Sciences journal.

Using data from 8,250 adults 65 and older who participated in the national Health and Retirement Study from 2010 to 2016, the researchers found that the index helped predict an increased risk of death during the period studied in a significant number of older adults, complementing medical tools used for this purpose.

“Our goal is to help clinicians identify older patients who are socially frail and to prompt problem-solving designed to help them cope with various challenges,” said Dr. Sachin Shah, a coauthor of the paper and a researcher at Massachusetts General Hospital.

“It adds dimensions of what a clinician should know about their patients beyond current screening instruments, which are focused on physical health,” said Dr. Linda Fried, a frailty researcher and dean of the Mailman School of Public Health at Columbia University.

Beyond the corridors of medicine, Fried said, “we need society to build solutions” to issues raised in the index — the ability of older adults to work, volunteer and engage with other people; the safety and accessibility of neighborhoods in which they live; ageism and discrimination against older adults; and more.

Meanwhile, a team of Chinese researchers recently published a comprehensive review of social frailty in adults age 60 and older, based on results from dozens of studies with about 83,900 participants in Japan, China, Korea and Europe. They determined that 24{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of these older adults, assessed both in hospitals and in the community, were socially frail — a higher portion than those deemed physically frail (12{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}) or cognitively frail (9{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}) in separate studies. Most vulnerable were people 75 and older.

What are the implications for health care? “If someone is socially vulnerable, perhaps they’ll need more help at home while they’re recovering from surgery. Or maybe they’ll need someone outside their family circle to be an advocate for them in the hospital,” said Dr. Kenneth Covinsky, a geriatrician at UC San Francisco and coauthor of the recent Proceedings of the National Academy of Sciences article.

“I can see a social frailty index being useful in identifying older adults who need extra assistance and directing them to community resources,” said Jennifer Ailshire, an associate professor of gerontology and sociology at the University of Southern California Leonard Davis School of Gerontology.

Older people who are socially vulnerable may need more assistance with health care.

Unlike other physicians, geriatricians regularly screen older adults for extra needs, albeit without using a well-vetted or consistent set of measures. “I’ll ask, ‘Who do you depend on most and how do you depend on them? Do they bring you food? Drive you places? Come by and check on you? Give you their time and attention?’ ” said Dr. William Dale, the Arthur M. Coppola family chair in supportive care medicine at City of Hope, a comprehensive cancer center in Duarte, California.

Depending on the patients’ answers, Dale will refer them to a social worker or help modify their plan of care. But he cautioned that primary care physicians and specialists don’t routinely take the time to do this.

Oak Street Health, a Chicago-based chain of 169 primary care centers for older adults in 21 states and recently purchased by CVS Health, is trying to change that in its clinics, said Dr. Ali Khan, the company’s chief medical officer of value-based care strategy.

At least three times a year, medical assistants, social workers or clinicians ask patients about loneliness and social isolation, barriers to transportation, food insecurity, financial strain, housing quality and safety, access to broadband services and utility services.

The organization combines these findings with patient-specific medical information in a “global risk assessment” that separates older people into four tiers of risk, from very high to very low. In turn, this informs the kinds of services provided to patients, the frequency of service delivery and individual wellness plans, which include social as well as medical priorities.

The central issue, Khan said, is “what is this patient’s ability to continue down a path of resilience in the face of a very complicated health care system?” and what Oak Street Health can do to enhance that.

What’s left out of an approach such as this, however, is something crucial to older adults: whether their relationships with other people are positive or negative. That isn’t typically measured, but it’s essential in considering whether their social needs are being met, said Linda Waite, the George Herbert Mead distinguished service professor of sociology at the University of Chicago and director of the National Social Life, Health, and Aging Project.

For older adults who want to think about their own social vulnerability, consider this five-item index, developed by researchers in Japan.

1. Do you go out less frequently compared with last year?

2. Do you sometimes visit your friends?

3. Do you feel you are helpful to friends or family?

4. Do you live alone?

5. Do you talk to someone every day?

Think about your answers. If you find your responses unsatisfactory, it might be time to reconsider your social circumstances and make a change.

Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study

Abstract

Objective To identify an optimal lifestyle profile to protect against memory loss in older individuals.

Design Population based, prospective cohort study.

Setting Participants from areas representative of the north, south, and west of China.

Participants Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009.

Main outcome measures Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), 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 drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample.

Results 29 072 participants were included (mean age of 72.23 years; 48.54{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} (n=14 113) were women; and 20.43{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52).

Conclusion A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.

Introduction

Although a fundamental function of daily life, memory continuously declines as people age,1 impairing both life quality and work productivity and increasing the risk of dementia.234 However, age related memory decline is not always a prodrome of dementia; memory loss can merely be senescent forgetfulness, which is more prevalent among older individuals, and can be reversed or become stable rather than progress to a pathological state.5 Thus, the prevention and slowing of age related memory decline in older individuals is paramount. Fortunately, memory decline can be mutable because various contributing factors are reportedly associated with memory loss.

Studies have been conducted to identify factors that might affect memory, including ageing, the apolipoprotein E (APOE) ε4 genotype, chronic diseases, and lifestyle patterns.67 Among these, lifestyle has received increasing attention as a modifiable behaviour because this factor is relatively easily amendable with potential benefits for overall health as well as memory. Studies on the effect of a healthy lifestyle on cognition are increasing.89101112 However, few studies have focused on its effect on memory, and most were cross sectional in nature,13 which is insufficient to evaluate the relationship between a long term healthy lifestyle and memory decline. Additionally, those studies did not consider the interaction between a healthy lifestyle and genetic risk; thus, the exact effect of a healthy lifestyle on memory decline in individuals with a higher genetic risk remains unknown. Therefore, longitudinal studies are needed to further investigate the effect of modifiable lifestyle factors on memory decline in older individuals, considering genetic risks, such as the presence of an APOE ε4 genotype.

We used data from a large population based cohort (the China Cognition and Ageing Study; COAST) to investigate whether adherence to a combination of healthy lifestyle factors was associated with a slower memory decline in cognitively normal older adults, even those genetically susceptible to memory decline.

Methods

Study design and participants

The COAST is a nationwide, population based, cohort study on dementia in China (ClinicalTrials.gov identifier: NCT03653156). This investigation included individuals from 12 provinces from the north, south, and west of China, representing the geographical characteristics, degree of urbanisation, economic status, dietary patterns, and cultural and social differences in China. We conducted a multistage, stratified, cluster sampling procedure, which considered sex and age distribution, among these provinces. A total of 96 study sites (48 urban and 48 rural) were randomly selected (supplementary 1). Written or oral informed consent was obtained from all participants.

The study enrolment procedure began on 8 May 2009 and comprised two sequential phases (lasting about six months together). In phase 1, individuals aged 60 years or older, who gave consent to participate in the study, were listed in the community census or village registry, and had resided there for at least one year preceding the survey date, were included in the study. We excluded participants with a life threatening disease, hearing loss, or vision loss. In phase 2, participants from phase 1 with available APOE genotyping and without mild cognitive impairment or dementia were included. Four rounds of follow-up were conducted—ie, a follow-up any time in 2012, 2014, 2016, and 2019. The end date of the study was 26 December 2019.

Diagnosis of dementia and mild cognitive impairment

The aim of this study was to investigate the association between lifestyle and memory in participants with normal cognitive function throughout the study period. Neuropsychological tests were done to determine the cognitive status of the participants at baseline and at each follow-up. For people who progressed to mild cognitive impairment or dementia during the follow-up period, the data after their diagnosis were excluded in the main analyses. Global cognitive function was assessed using the Mini-Mental State Examination,14 which evaluates orientation, attention, calculation, executive function, language, among others. The total score of the Mini-Mental State Examination ranges from 0 to 30, with higher scores representing a better cognitive function. Participants whose score was less than 26 were suspected of cognitive impairment and would receive further evaluation, including physical and other neuropsychological testing. The results and participants’ medical records were reviewed by neurologists who were masked to the genetic results. Dementia was diagnosed on the consensus of at least two neurologists, according to the Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision criteria).15 Mild cognitive impairment was diagnosed according to the Peterson criteria.16 Having normal cognitive function was defined as having a score of 0 for the Clinical Dementia Rating.17 People for whom a consensus could not be reached were considered controversial cases. These cases would be discussed and diagnosed by an expert group, which included senior neurologists, psychiatrists, and neuropsychologists.

Assessment of lifestyle factors

Lifestyle information was collected at baseline and each follow-up based on each individual’s performance over the past year through a healthy behaviour questionnaire (supplementary 2). We assessed lifestyle status by six modifiable lifestyle factors: physical exercise, diet, drinking, smoking, cognitive activity, and social contact. For physical exercise, weekly frequency and total time were collected, and at least 150 min of moderate or 75 min of vigorous activity per week was considered a healthy factor, according to the American guidelines for physical activity in adults.18 For smoking, participants were categorised as smokes current, never (participants who had smoked <100 cigarettes in their lifetime) smokes, or used to smoke (participants who had quit smoking at least three years before). Never or former smoking was deemed a healthy lifestyle factor.19 For alcohol consumption, the current frequency and volume of alcohol consumption were recorded, and individuals were categorised into never drinking (never drank or drank occasionally), low to excess drinking (daily alcohol consumption of 1-60 g), and heavy drinking (daily alcohol consumption >60 g).20 The category of never drinking was deemed a healthy lifestyle factor.21 The remaining three lifestyle factors were deemed healthy based on the top 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of the population distribution, according to previous studies.22232425 For diet, we recorded the participant’s daily intake of 12 food items (fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, and tea) (supplementary 2).26 For cognitive activity (writing, reading, playing cards, mahjong, and other games) and social contact (participation in meetings or attending parties, visiting friends or relatives, travelling, and chatting online), engagement frequencies were investigated. Ultimately, these factors were deemed healthy when participants consumed appropriate daily amounts of at least 7 of the 12 food items for diet, and they engaged in cognitive activity or social contact at least twice weekly in this study.

We evaluated the association of each single lifestyle factor with memory function. For further investigation of the combined effect of lifestyle factors on memory function, we categorised participants into three groups based on the third of the number of healthy lifestyle factors: favourable (4-6 healthy factors), average (2-3), and unfavourable (0-1). To investigate the effect of lifestyle on memory stratified by APOE genotypes, participants were also grouped into people who were APOE ε4 carriers and people who were not carriers.

Outcomes

Memory function was measured at baseline and each follow-up using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT),27 which included measurement of immediate recall, short delay free recall (3 min later), long delay free recall (30 min later), and long delay recognition. During the test, a rater read a list of words consisting of 15 nouns; immediately after its completion, the participant attempted to repeat as many words as possible. The score of immediate recall was 0-60, and the scores of all other tests were 0-15. The standard z scores for the auditory verbal learning test were calculated based on the respective mean and standard deviation test scores. The composite z score for memory function was constructed by averaging the z scores for each test in the auditory verbal learning test.

Covariates

Potential confounders were selected based on directed acyclic graphs (supplementary figure 1) depicting the best known relations between the variables in this study. Sociodemographic information obtained at baseline were sex, place of residence (rural or urban), region (north, west, or south), marital status (married, widowed, or divorced/separated/single), years of education (<1 year, 1-6 years, 7-12 years, >12 years), monthly household income (1000-2999, 3000-4999, 5000-10 000, >10000 Chinese Yuan), occupation (manual labourer, office worker, household, or others). Health related covariates were collected at baseline and each follow-up, including age, body mass index and medical illnesses (hypertension, diabetes, hyperlipidaemia, heart attack, head injury, cerebrovascular disease, and depression). We also included the learning effect of each participant as a covariate due to repeated cognitive assessments.

Statistical analysis

Baseline characteristics of the analytical sample were summarised across three lifestyle groups as a percentage for categorical variables and mean and standard deviation for continuous variables. Missing values are summarised in supplementary table 1. A multiple imputation chain-equation was used to impute missing data. Data were assumed to be missing at random. Missing continuous variables were imputed using predictive mean matching method, and binary variables were imputed by Logistic regression model. We generated five imputed datasets with 100th iteration, and analysed each dataset separately, then combined their results by use of Rubin’s method.

Linear mixed effects models were used in this study, and all statistical assumptions were tested before interpretation of results. The data met the distributional requirements in each case. We examined the effects of different lifestyle profiles, APOE ε4 status, as well as their interactions on longitudinal memory trajectories in participants with normal cognition throughout the study by use of linear mixed effects models. The composite z score of the auditory verbal learning test was the dependent variable. The fixed effects were the following: lifestyle profiles (each respective lifestyle factor as well as the combination); APOE ε4 status; time (follow-up year from baseline); two way interactions of lifestyle with APOE ε4 status and time; and three way interactions between lifestyle, APOE ε4 status, and time. The random effects included intercept and time. Age (centred at 74 years to reduce the correlation between the age and age squared terms), age squared (to allow for the comparison of acceleration in the rate of memory decline between lifestyle groups), baseline memory score, learning effect (by assignment code to the first assessment as 1 versus subsequent assessments coded as 0), and other covariates were also adjusted in this model. In addition, the global cognitive trajectories in the cognitively normal population were evaluated using a linear mixed effects model with global cognition (standard z score of the Mini-Mental State Examination) as dependent variable. Furthermore, we investigated the interaction between lifestyle and age on memory decline.

As lifestyle status and some of the covariates changed over time, a time dependent Cox regression model (non-proportional hazard model) was used to assess the effect of lifestyle groups on progression to mild cognitive impairment or dementia in the total study population and APOE ε4 stratified population. In this model death and drop-out data were treated as censoring data. Additionally, we evaluated whether dropping out from the study affected the effects of lifestyle on mild cognitive impairment or dementia using an inverse probability weighting model. We also assessed the influence of death as a competing risk for mild cognitive impairment or dementia via competing risk analyses.

Sensitivity analyses

We conducted several additional sensitivity analyses to evaluate the robustness of our findings. Firstly, we included the number of lifestyle factors as a continuous variable in the mixed model to test the rationale of our grouping method. Secondly, we derived a weighted standardised healthy lifestyle score based on the β coefficient of each lifestyle factor in the linear mixed effects model adjusted for covariates.28 Specifically, the original binary lifestyle variables were multiplied by the β coefficients, and all the β coefficients were summed. The score of each lifestyle factor was obtained via the β coefficient of each lifestyle factor divided by the sum of the β coefficients, multiplied by 100. Participants were categorised into three groups based on the third of weighted standardised score into low, intermediate, and high score groups. Third, we excluded each lifestyle factor to identify possible factors that might drive the associations with memory. The excluded lifestyle factor was used as a confounder. Fourthly, we excluded participants who later developed mild cognitive impairment or dementia to determine whether the results were consistent with the main results. Fifthly, we excluded participants who died or dropped out throughout the study in order to evaluate the possible effects of death or drop-out on the results (if the results were consistent when participants were excluded with when they were not excluded, death or drop-out would have had no effect on the results). Finally, to assess the reverse causality of memory decline and healthy lifestyle profile, we performed a cross-lagged panel model, which is used when examining reciprocal causal processes in longitudinal data with at least two waves of data. Each analysis included a cross-wave component that estimated the change in each outcome from one wave, characterised by relationships between outcomes from each specific wave. We examined changes in composite z scores for memory in relation to changes in healthy lifestyle profiles over time.

All statistical analyses were done in R (version 3.6.3). We used the following packages: mice, for imputing; lmerTest, for linear mixed effects models; cmprsk, for competing risk models; lavaan, for cross-lagged analysis; and ipw, for inverse probability weighting. The two tailed significance level was set at P<0.05.

Patient and public involvement

Participants of the COAST study were not involved in setting the research question or the outcome measures, nor were they involved in developing plans for recruitment, design, or implementation of the study. No participants were asked for advice on interpreting or writing up of results. We know that the public involvement has great value in improving the quality of research; however, we did not have the necessary funding to invite participants for their advice. We intend to engage participants and the public to disseminate the results of our study.

Results

In total, 56 894 individuals were screened for eligibility. In phase 1, we excluded 17 148 individuals who were younger than 60 years or did not give permission to participate. In total, 39 746 individuals completed the neuropsychological assessment and clinical examination. In phase 2, we excluded 7814 individuals with mild cognitive impairment and 2860 individuals with dementia. Overall, we enrolled 29 072 with normal cognitive function who underwent APOE genotyping at baseline. During the 10 year follow-up period, 7164 individuals died and 3567 individuals discontinued participation for various reasons (fig 1).

Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study
Fig 1

Study profile. MCI=mild cognitive impairment

Table 1 summarises the participants’ baseline demographic characteristics according to the three lifestyle groups. At baseline, all participants had normal cognitive function (48.54{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} female), with a mean age of 72.23 years (standard deviation 6.61), and 20.43{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} were carriers of APOE ε4 (supplementary table 2). Additionally, 6967 participants were enrolled in the unfavourable lifestyle group, 16 549 in the average group, and 5556 in the favourable group.

Table 1

Demographic characteristics of the cognitively normal population and time dependent healthy lifestyle groups at baseline. Data are number ({bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}), unless otherwise specified

Lifestyle and memory function in older adults

We used linear mixed effects models to describe the trends in global cognition and memory function and to examine the influence of healthy lifestyle and APOE ε4 status on the annual rate of change in memory function over the 10 year follow-up period. The trajectories in the population with normal cognitive function indicated that, although the overall cognition state remained stable, memory declined continuously over time (supplementary figure 2, supplementary tables 3-4). This memory decline occurred faster in the APOE ε4 carriers than in the APOE ε4 non-carriers (0.002 points/year, 95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.001 to 0.003, P=0.007) (supplementary figure 2, supplementary table 5).

We evaluated the contribution of each binary lifestyle component on memory decline. The results showed that a healthy diet had the strongest effect on memory (β=0.016, 95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.014 to 0.017, P<0.001), followed by active cognitive activity (β=0.010, 0.008 to 0.012, P<0.001), regular physical exercise (β=0.007, 0.005 to 0.009, P<0.001), active social contact (β=0.004, 0.002 to 0.006, P<0.001), never or former smoking (β=0.004, 0.000 to 0.008, P=0.026), and never drinking (β=0.002, 0.000 to 0.004, P=0.048) (supplementary table 6). Furthermore, we analysed the association between lifestyle groups and memory performance. Our results showed that participants with favourable and average lifestyles had a slower rate of memory decline than did participants with an unfavourable lifestyle (P<0.001) (fig 2). Specifically, the decline in the composite z score was slower by 0.028 points/year (95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.023 to 0.032) in the favourable group and by 0.016 points/year (0.012 to 0.020) in the average group than in the unfavourable group. Figure 2 (bottom panel) shows that the mean composite Auditory Verbal Learning Test scores continuously declined over the 10 year period; the highest test scores were observed in the favourable group and the lowest in the unfavourable group.

Fig 2
Fig 2

Longitudinal change in memory among favourable, average, and unfavourable groups in the cognitively normal population. (Top panel) Estimated change in memory function over 10 years, by group. Dots represent individuals’ estimated composite z scores for AVLT. (Bottom panel) Mean composite AVLT z scores of all groups. AVLT=Auditory Verbal Learning Test

Assessing the interaction between lifestyle and age showed a slower rate of age related memory decline in the favourable and average lifestyle groups compared with that in the unfavourable group. Compared with the unfavourable group, the memory score in the favourable lifestyle group was 0.007 (95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.005 to 0.009, P<0.001) points higher per increased year of age and in the average group was 0.002 (0.000 to 0.003, P=0.033) (supplementary table 7).

Lifestyle and memory function in people with or without APOE ε4

Similar results were obtained in the analyses that were stratified according to the APOE genotype (fig 3). In people who carry APOE ε4 allele and in people who do not, a favourable lifestyle was associated with better memory performance over time compared with average and unfavourable lifestyles (P<0.001). Among people who carry APOE ε4, participants with favourable and average lifestyles exhibited a slower rate of memory decline than did those with an unfavourable lifestyle (0.027 (95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.023 to 0.031) and 0.014 (0.010 to 0.019) points/year, respectively). Among people who did not carry the APOE ε4 allele, the estimated rates of decline were 0.029 (0.019 to 0.039) points/year slower for participants with favourable lifestyles and 0.019 (0.011 to 0.027) for participants with average lifestyles, compared with participants who had an unfavourable lifestyle. Further analysis showed no significant interaction effect between APOE ε4 status and lifestyle profiles on memory decline (P=0.52).

Fig 3
Fig 3

Longitudinal change in memory among favourable, average, and unfavourable groups in the APOE ε4 stratified population. Dots in the left panels represent individuals’ estimated composite AVLT z scores. AVLT=Auditory Verbal Learning Test; APOE=apolipoprotein E

Lifestyle and mild cognitive impairment or dementia

Time dependent Cox regression models suggest that, over 10 years of follow-ups, a favourable lifestyle was associated with a lower probability of progression to mild cognitive impairment and dementia. Compared with an unfavourable lifestyle, the hazard ratios were 0.71 (95{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} confidence interval 0.68 to 0.73) for an average lifestyle and 0.11 (0.10 to 0.12) for a favourable lifestyle. The result was similar when considering the competing risk of death (supplementary table 8). The inverse probability weighting model showed that participants who dropped out of the study did not affect the association between lifestyle and mild cognitive impairment or dementia (supplementary table 9). The APOE stratified analysis showed a similar result with that of the total population (supplementary table 8).

The relations between the mean auditory verbal learning test score and the percentage of participants with dementia or mild cognitive impairment are presented in figure 4. The percentage of participants with dementia or mild cognitive impairment increased as the mean Auditory Verbal Learning Test scores decreased among the older adults in our study.

Fig 4
Fig 4

Mean AVLT scores and the percentage of participants with dementia (top panel) and mild cognitive impairment (bottom panel) among older adults, at different follow-up periods. The percentages of participants with dementia and mild cognitive impairment increase with a reduction in the mean AVLT scores. AVLT=Auditory Verbal Learning Test; MCI=mild cognitive impairment

Sensitivity analyses

The results of the sensitivity analyses are presented in the supplementary material. The first sensitivity analysis was conducted to test the robustness of the rationale of our grouping methods. When the number of lifestyle factors was considered as a continuous variable in the mixed effects model, two or more healthy lifestyle factors were associated with a slower rate of memory decline than did no healthy factors (supplementary table 10). The results of the analysis investigating the association between lifestyle and memory based on the weighted standardised healthy lifestyle scores showed that participants in the high and intermediate score groups had a slower rate of memory decline by 0.029 (0.025 to 0.033, P<0.001) and 0.017 (0.015 to 0.019, P<0.001) points/year, respectively, compared with participants in the low score group (supplementary tables 11-12). We found that no particular healthy lifestyle factor drove the association between lifestyle and memory (supplementary table 13). Additionally, among participants who did not develop mild cognitive impairment or dementia, did not drop out, and were alive throughout the follow-up period, the association between lifestyle profiles and memory decline remained significant (supplementary tables 14-15). Cross lagged analyses were done to assess the bidirectional, longitudinal associations between memory function and a healthy lifestyle during the 10 year follow-up period. The results supported the absence of a reverse causality between memory decline and healthy lifestyle profiles (supplementary figure 3).

Discussion

This large scale study is the first to our knowledge to estimate the effects of different lifestyle profiles, APOE ε4 status, and their interactions on longitudinal memory trajectories over a 10 year follow-up period. Our results show that a healthy lifestyle was associated with a slower rate of memory decline in cognitively normal older individuals, including in people who are genetically susceptible to memory decline.

Comparison with other studies

This study characterised the longitudinal memory trajectories of the participants with normal global cognition. Of note, the results showed that, although global cognition remained relatively stable, memory declined rapidly as the individual aged. Therefore, focusing on global cognition might lead to overlooking memory problems, especially among people older than 65 years, a third of whom are reported to experience memory complaints.29 Effective strategies for protecting against memory decline might benefit many older individuals. Previous studies have investigated the associations between lifestyle factors and memory loss; however, most have focused on a single lifestyle factor, such as smoking,30 drinking,3132 diet,33 or physical activities.734 Few studies have been conducted to target the combined effects of multiple lifestyle factors on memory decline. Thus, comparison of the contribution of each factor to memory decline has been a challenge.

In this study, we investigated the contribution of each lifestyle factor and their combined effects in a large sample size over an entire decade. We found that diet had the strongest association with memory, followed by cognitive activity, physical exercise, and social contact. Although each lifestyle factor contributed differentially to slowing memory decline, our results showed that participants who maintained more healthy lifestyle factors had a significantly slower memory decline than those with fewer healthy lifestyle factors. This information could be useful in making personal choices that can help to protect against memory decline, and our results provide further evidence that memory loss is potentially modifiable. Although the mechanisms responsible for such changes were not determined in this study, they might include reduced cerebrovascular risk, enhancement of cognitive reserve, inhibition of oxidative stress and inflammation, and promotion of neurotrophic factors.11133536

Another defining feature of our study is that all participants underwent APOE genotyping. The APOE ε4 allele is reportedly correlated with earlier and more rapidly progressive memory decline,137 and the frequency of the ε4 allele dramatically increases to 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} in patients with Alzheimer’s disease.38 People who have the APOE ε4 allele are more likely to exhibit abnormally high Aβ levels in the brain and experience more rapid neurodegeneration and memory loss than people who do not.39404142 The APOE ε4 allele can also magnify the effects of other risk factors, including physical inactivity, unhealthy diet, and smoking.43 However, most studies that have explored the role of APOE have focused on the associations between lifestyle and global cognition rather than memory.444546 Here, we observed a positive effect of a healthy lifestyle on memory in both carriers of APOE ε4 and non-carriers, and no interaction effect was observed between the APOE genotype and lifestyle profiles over time. These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors are associated with a slower rate of memory decline, regardless of the genetic risk.

Strengths and limitations of this study

Although many studies have investigated the relationship between a healthy lifestyle and dementia, few have focused on memory loss, which is a condition that older adults with normal cognitive function can experience and that differs from dementia. This multicentre study with a large sample and a long term follow-up period provided an opportunity to observe the longitudinal trajectories of memory function in older adults with different lifestyles. However, our study also has some limitations. Firstly, the assessments of lifestyle factors were based on self-reports and are, therefore, prone to measurement errors. Secondly, several participants were excluded due to missing data or not returning for follow-up evaluations, which might have led to selection bias. Thirdly, the proportion of individuals with an unhealthy lifestyle might have been underestimated in our study because people with poor health were less likely to have participated in the study. Fourthly, given the nature of our study design, we could not assess whether maintaining a healthy lifestyle had already started influencing memory by the time of enrolment in the study. Fifthly, we evaluated memory using a single neuropsychological test that does not comprehensively reflect overall memory function. However, the Auditory Verbal Learning Test is an effective instrument for memory assessment, and we used a composite score based on four Auditory Verbal Learning Test subscales to represent memory conditions to the greatest extent possible. Sixthly, as participants might become familiar with repeated cognitive testing, a learning effect could have influenced the results, although, we considered that possibility in the design of the statistical analysis method. Finally, we studied memory decline solely among older adults; however, memory problems commonly affect young individuals as well. Thus, further studies should be conducted to facilitate a more extensive investigation into the effects of a healthy lifestyle on memory decline across the lifespan. This approach would help to elucidate the crucial age window during which a healthy lifestyle can exert the most favourable effect.

Conclusions

The results of this study provide strong evidence that adherence to a healthy lifestyle with a combination of positive behaviours, such as never or former smoking, never drinking, a healthy diet, regular physical exercise, and active cognitive activity and social contact, is associated with a slower rate of memory decline. Importantly, our study provides evidence that these effects also include individuals with the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.

What is already known on this topic

  • Memory is a fundamental function of daily life that continuously declines with increasing age

  • Evidence from cohort studies is insufficient to evaluate the effect of healthy lifestyle on memory trajectory

  • Given the multifactorial biological cause of memory decline, a combination of healthy lifestyle factors might be necessary for an optimal effect, even for people who are genetically susceptible to memory decline

What this study adds

  • A combination of positive healthy behaviours is associated with a slower rate of memory decline in cognitively normal older adults, including in people with the apolipoprotein E ε4 allele

  • These results might offer important information for public health initiatives to protect older adults against memory decline

What Older Americans Need to Know About Taking Paxlovid

Judith Graham

A new coronavirus variant is circulating, the most transmissible one yet. Hospitalizations of infected sufferers are climbing. And older adults characterize nearly 90{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of U.S. fatalities from covid-19 in recent months, the major portion considering that the begin of the pandemic.

What does that necessarily mean for people today 65 and older catching covid for the 1st time or people dealing with a repeat an infection?

The concept from infectious disease professionals and geriatricians is very clear: Find cure with antiviral treatment, which stays effective towards new covid variants.

The remedy of 1st selection, professionals explained, is Paxlovid, an antiviral cure for people with moderate to moderate covid at superior danger of getting seriously ill from the virus. All older people 65 and up slide in that class. If folks cannot tolerate the medicine — probable troubles with other medications have to have to be meticulously evaluated by a clinical service provider — two possibilities are out there.

“There’s tons of evidence that Paxlovid can decrease the risk of catastrophic occasions that can adhere to an infection with covid in older men and women,” reported Dr. Harlan Krumholz, a professor of medicine at Yale College.

In the meantime, acquire a program for what you will do if you get covid. Exactly where will you look for treatment? What if you simply cannot get in rapidly to see your medical professional, a common trouble? You require to act rapid since Paxlovid need to be commenced no afterwards than five times right after the onset of signs or symptoms. Will you have to have to regulate your medicine program to guard against possibly perilous drug interactions?

“The time to be figuring all this out is ahead of you get covid,” said Dr. Allison Weinmann, an infectious-illness pro at Henry Ford Clinic in Detroit.

Becoming organized proved necessary when I caught covid in mid-December and went to urgent treatment for a prescription. Mainly because I’m 67, with blood most cancers and autoimmune illness, I’m at elevated hazard of receiving seriously ill from the virus. But I just take a blood thinner that can have life-threatening interactions with Paxlovid.

Thankfully, the urgent care center could see my electronic healthcare report, and a physician’s be aware there reported it was safe for me to end the blood thinner and get the treatment method. (I’d consulted with my oncologist in advance.) So, I walked away with a Paxlovid prescription, and within a working day my headaches and chills had disappeared.

Just before obtaining covid, I’d study an essential research of almost 45,000 people 50 and more mature taken care of for covid concerning January and July 2022 at Mass Basic Brigham, a massive Massachusetts wellbeing program. 20-8 {bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of the patients had been prescribed Paxlovid, which experienced been given an unexpected emergency use authorization for moderate to moderate covid from the Fda in December 2021 72{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} had been not. All were outpatients.

In contrast to in other studies, most of the patients in this one particular experienced been vaccinated. Nonetheless, Paxlovid conferred a noteworthy gain: People who took it ended up 44{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} much less likely to be hospitalized with serious covid-relevant illnesses or die. Amid people who’d gotten much less than a few vaccine doses, these hazards were reduced by 81{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}.

A couple of months earlier, a research out of Israel had confirmed the efficacy of Paxlovid — the brand name name for a blend of nirmatrelvir and ritonavir — in seniors contaminated with covid’s omicron strain, which arose in late 2021. (The primary examine developing Paxlovid’s performance experienced been carried out though the delta strain was commonplace and provided only unvaccinated people.) In individuals 65 and more mature, most of whom experienced been vaccinated or formerly experienced covid, hospitalizations have been lowered by 73{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} and fatalities by 79{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}.

Continue to, several aspects have obstructed Paxlovid’s use amid older grown ups, which include doctors’ considerations about drug interactions and patients’ issues about probable “rebound” bacterial infections and facet outcomes.

Dr. Christina Mangurian, vice dean for school and academic affairs at the College of California-San Francisco School of Medicine, encountered several of these issues when both equally her mom and dad caught covid in July, an episode she chronicled in a latest JAMA write-up.

Initial, her father, 84, was explained to in a virtual health care appointment by a medical professional he didn’t know that he couldn’t consider Paxlovid for the reason that he’s on a blood thinner — a determination afterwards reversed by his principal care medical professional. Then, her mom, 78, was informed, in a separate digital appointment, to get an antibiotic, steroids, and over-the-counter medicines rather of Paxlovid. The moment yet again, her most important treatment medical doctor intervened and presented a prescription.

In equally circumstances, Mangurian stated, the medical doctors her moms and dads initial saw appeared to misunderstand who ought to get Paxlovid, and underneath what situations. “This details to a big deficit in phrases of how info about this remedy is getting disseminated to entrance-line clinical providers,” she informed me in a cell phone dialogue.

Michael Osterholm, director of the Center for Infectious Disorder Investigate and Policy at the College of Minnesota, agrees. “Every working day, I listen to from persons who are misinformed by their medical professionals or contact-in nurse strains. Usually, they are remaining informed you just can’t get Paxlovid right up until you’re very seriously ill — which is just the opposite of what’s encouraged. Why are we not undertaking extra to teach the healthcare group?”

The possible for drug interactions with Paxlovid is a important concern, specially in more mature patients with a number of clinical ailments. A lot more than 120 medicines have been flagged for interactions, and each and every case needs to be evaluated, having into account an individual’s problems, as effectively as kidney and liver perform.

The great news, gurus say, is that most potential interactions can be managed, either by quickly halting a medicine though getting Paxlovid or minimizing the dose.

“It can take a small added function, but there are methods and techniques in location that can support practitioners figure out what they should really do,” stated Brian Isetts, a professor at the College of Minnesota College or university of Pharmacy.

In nursing households, clients and people really should inquire to talk to expert pharmacists if they’re explained to antiviral therapy is not advisable, Isetts advised.

About 10{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of patients cannot get Paxlovid due to the fact of probable drug interactions, according to Dr. Scott Dryden-Peterson, professional medical director of covid outpatient therapy for Mass Typical Brigham. For them, Veklury (remdesivir), an antiviral infusion remedy shipped on a few consecutive days, is a very good option, though often difficult to arrange. Also, Lagevrio (molnupiravir), an additional antiviral tablet, can assistance shorten the period of symptoms.

Lots of older adults concern that following taking Paxlovid they’ll get a rebound infection — a unexpected resurgence of symptoms following the virus appears to be to have run its class. But in the wide bulk of circumstances “rebound is incredibly moderate and signs or symptoms — commonly runny nose, nasal congestion, and sore throat — go absent in a few times,” reported Dr. Rajesh Gandhi, an infectious-sickness health practitioner and professor of drugs at Harvard Health-related Faculty.

Gandhi and other physicians I spoke with mentioned the chance of not dealing with covid in older older people is significantly greater than the chance of rebound illness.

Facet consequences from Paxlovid include things like a metallic style in the mouth, diarrhea, nausea, and muscle mass aches, amongst other individuals, but critical troubles are unusual. “Consistently, people are tolerating the drug truly properly,” claimed Dr. Caroline Harada, associate professor of geriatrics at the College of Alabama-Birmingham Heersink School of Medication, “and experience greater quite swiftly.”

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