Risk Of Dementia In Later Life Research Articles

Midlife aspiration and optimism to improve status at work is associated with lower risk for late life dementia

Background:Vascular risk is consistently associated to the onset of dementia. Schooling and cardiovascular (CV) risk factors might have an impact on the rate of progression of Alzheimer’s disease (AD).Methods: Forty-seven patients with probable AD were recruited and classified in two groups according to their score on the Mini-Mental State Examination (MMSE): patients scoring 20 within 3 years after disease onset. Additionally, twenty-six patients who had already scored 15 were classified in two groups: patients scoring 15 within 4 years after disease onset. Also, forty patients with a score > 1.0 on the Clinical Dementia Rating (CDR) were allocated into one of two groups: patients reaching a score > 1.0 within 1⁄44 years after disease onset. Patients were assessed for gender, schooling ( 4 years), age of estimated disease onset ( 1⁄470 years), number of CV risk factors (>1⁄43, or 1⁄470kgf, or 1⁄430kg/m, or ) and waist circumference (> 1⁄4102cm, orChi-squarewas used for statistics, with the threshold of significance at ? 1.0, there were no significant results for gender (?1⁄40.702), schooling (?1⁄40.507), age at disease onset (?1⁄40.666), BMI (?1⁄40.926), weight (?1⁄40.169) or waist circumference (?1⁄40.787). Cumulative CV risk was non-significant for reaching CDR> 1.0 (?1⁄40.641), MMSE1⁄420 (?1⁄4 0.861) or MMSE1⁄415 (?1⁄40.716).Conclusions:Weight and lower schooling had marginally significant effects for a faster rate of progression of AD, assessed by way of MMSE scores.

Journal Digest

Journal Digest

Midlife overweight and obesity increase late-life dementia risk

The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association. From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes. Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019). Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.

Life-Course Socioeconomic Position and Incidence of Dementia and Cognitive Impairment Without Dementia in Older Mexican Americans: Results From the Sacramento Area Latino Study on Aging

There have been few investigations of the link between changes in life-course socioeconomic position (SEP) and cognitive decline or incidence of dementia. The authors examined the impact of changes in life-course SEP on incidence of dementia and cognitive impairment but not dementia (CIND) over a decade of follow-up. Participants of Mexican origin (n = 1,789) were members of the Sacramento Area Latino Study on Aging cohort. Incidence of dementia/CIND was ascertained by using standard diagnostic criteria. SEP indicators at 3 life stages (childhood, adulthood, and midlife) were used to derive a measure of cumulative SEP (range, 0 to 8) and SEP mobility. Nearly 24% of the sample maintained a low SEP throughout life. Hazard ratios and 95% confidence intervals were computed from Cox proportional hazards regression models. In fully adjusted models, participants with a continuously high SEP had lower hazard ratios for dementia/CIND compared with those with a continuously low SEP at all 3 life stages (hazard ratio = 0.49, 95% confidence interval: 0.24, 0.98; P = 0.04). In age-adjusted models, participants experienced a 16% greater hazard of dementia/CIND with every 1-unit increase in cumulative SEP disadvantage across the life course (hazard ratio = 1.16, 95% confidence interval: 1.01, 1.33; P = 0.04). Early exposures to social disadvantage may increase the risk of late-life dementia.

Risk of Incident Dementia in Drug-Untreated Arterial Hypertension: A Population-Based Study

Arterial hypertension in midlife may increase the risk of late-life dementia. Notably, there is conflicting data as to whether hypertension in the elderly (age 65 years and older) is a risk factor for dementia and Alzheimer's disease (AD). We determined whether drug-untreated hypertension was associated with a higher risk of incident dementia and AD. In a population-based study of older people in central Spain (NEDICES), non-demented participants were followed prospectively. Dementia at follow-up was diagnosed using DSM-IV criteria. Using Cox proportional hazards models, the risk of dementia was estimated in participants with drug-untreated hypertension and in participants with drug-treated hypertension versus controls. The 3,824 participants had a mean duration of follow-up of 3.2 years. Sixty-two (3.3%) of 1,870 participants without baseline hypertension developed incident dementia versus 78 (4.7%) of 1,657 with drug-treated, baseline hypertension and 19 (12.0%) with drug-untreated, baseline hypertension. In an unadjusted Cox model, risk of dementia was increased in participants with drug-untreated hypertension (relative risk [RR] =1.93, 95% confidence interval [CI]=1.15–3.23, p = 0.01) and in participants with drug-treated hypertension (RR =1.43, 95% CI= 1.02–2.0, p =0.035) versus participants without hypertension (reference group). In a fully adjusted Cox model, the risk of dementia remained increased in participants with drug-untreated hypertension (RR =2.38, 95% CI =1.32–4.29, p=0.004). Results were similar for risk of AD. Our results suggest that drug-untreated hypertension may be an independent risk factor for dementia and AD in the elderly.

The Effect of Midlife Physical Activity on Cognitive Function Among Older Adults: AGES—Reykjavik Study

There are few studies on the long-term associations of physical activity (PA) to cognition. Here, we examine the association of midlife PA to late-life cognitive function and dementia. The sample consisted of a population-based cohort of men and women (born in 1907-1935) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. The interval between the midlife ascertainment of PA and late-life cognitive function was 26 years. Composite scores of speed of processing, memory, and executive function were assessed with a battery of neuropsychological tests, and dementia was diagnosed according to international guidelines. There were 4,761 nondemented participants and 184 (3.7%) with a diagnosis of dementia, with complete data for the analysis. Among the participants, no midlife PA was reported by 68.8%, ≤ 5 hours PA by 26.5%, and >5 hours PA by 4.5%. Excluding participants with dementia compared with the no PA group, both PA groups had significantly faster speed of processing (≤ 5 hours, β = .22; >5 hours, β = .32, p trend < .0001), better memory (≤ 5 hours, β = .15; >5 hours, β = .18, p trend < .0001), and executive function (≤ 5 hours, β = .09; >5 hours, β = .18, p trend< .0001), after controlling for demographic and cardiovascular factors. The ≤ 5 hours PA group was significantly less likely to have dementia in late life (odds ratio: 0.6, 95% confidence interval: 0.40-0.88) after adjusting for confounders. Midlife PA may contribute to maintenance of cognitive function and may reduce or delay the risk of late-life dementia.

Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia.

Unresolved issues in dementia research include (1) the association between nonstroke cardiovascular disease (CVD) and Alzheimer disease (AD) and (2) whether the association between CVD and dementia is mediated by familial factors (ie, genes and early life environment). We therefore conducted a study with both a longitudinal and a co-twin control design in 2214 Swedish twins with clinical dementia evaluation and apolipoprotein E (ApoE) genotyping. The analyses were then replicated in a register-based cohort of 18,405 individuals. Results show that CVD increases the risk of AD in carriers (but not noncarriers) of the ApoE4 allele (hazard ratio 2.39, 95% confidence interval 1.15-4.96). CVD was also associated with an almost 2-fold increased risk of developing late-life dementia (hazard ratio 1.83, 95% confidence interval 1.23-2.72). Within twin pairs, the dementia-affected twin was more likely to have had CVD than the nondemented twin partner (odds ratio 1.86, 95% confidence interval 1.11-3.13). In conclusion, this study shows that (1) nonstroke CVD increases the risk of late-life dementia but that it is only a risk factor for AD in carriers of the ApoE4 allele and (2) the association between CVD and dementia is not explained by genetic or early life environmental factors in common to both disorders.

Sex hormone binding globulin (SHBG) and dementia over 32 years: The Prospective Population Study of Women

We have shown that high mid-life central adiposity may increase risk for dementia. The influence of sex hormones is unclear. Sex hormone binding globulin (SHBG) is inversely correlated with adiposity measures, involved in sex hormone metabolism, and may contribute to a better etiological understanding of this relationship. A baseline measure of serum SHBG from the Prospective Population Study of Women in Sweden, was related to dementia over 32 years follow-up. A representative sample of 1462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992 and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline SHBG. Logistic regression models related SHBG levels to dementia among surviving participants 32 years later. All models were adjusted for multiple potential confounders. Baseline SHBG was not related to dementia risk using Cox or logistic models. This was observed despite inverse correlations between baseline SHBG and adiposity measures, and given our previous report of high mid-life WHR related to a two-fold higher dementia risk. While mid-life SHBG levels are inversely correlated to adiposity measures cross-sectionally in mid-life, it is not a marker of late-life dementia risk.

Lowering Midlife Levels of Systolic Blood Pressure as a Public Health Strategy to Reduce Late-Life Dementia

To estimate the potential benefits of lowering systolic blood pressure (SBP) toward preventing late-life dementia, we estimated the population-attributable risk of elevated SBP for dementia. Analyses are based on the cohort of 8006 Japanese American men (born 1900-1919) followed since 1965 as a part of the Honolulu Heart Program, continued as the Honolulu Asia Aging Study. Midlife cardiovascular risk factors and late-life brain function are well described. We estimated the population-attributable risk of dementia cases attributed to midlife SBP, grouped by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria (<120, 120 to <140, and > or =140 mm Hg), taking into account treatment history, confounding factors, and competitive risk for death. The analysis is based on 7878 subjects, including 491 cases of dementia, with a mean interval of 25 years between measurement of blood pressure and dementia diagnosis. Compared with those with SBP <120 mm Hg, untreated, and <50 years of age at baseline, 17.7% (95% CI: 4.6% to 29.1%) of the cases were attributable to prehypertensive levels (SBP: 120 to <140 mm Hg) of SBP, translating into 11 excess cases per 1000. Among those who did not report taking antihypertensive medication in midlife, 27% (95% CI: 8.9% to 42.1%) of dementia cases can be attributed to systolic BP > or =120 mm Hg, translating into 17 excess cases per 1000. Although population-attributable risk estimates for population subgroups may differ by relative risk for dementia or prevalence of elevated levels of blood pressure, these data suggest that reducing midlife systolic BP is an effective prevention strategy to reduce risk for late-life dementia.

Advances in Vascular Cognitive Impairment

Advances in Vascular Cognitive Impairment

Assessing the risk of dementia in the aging population

A method for determining which patients are at a high risk of developing dementia could improve preventative care, early diagnosis, and the identification of individuals for clinical trials. The late-life dementia risk index has been developed to fulfill this need in older adults, but does the model provide sufficient accuracy and reliability in assessing such risk?

Healthy Diet at Midlife and the Risk of Late-Life Dementia and Alzheimer's Disease: A Population-based CAIDE Study

Healthy Diet at Midlife and the Risk of Late-Life Dementia and Alzheimer's Disease: A Population-based CAIDE Study

Preventive neurology

Neurology has long been a specialty where symptoms of disease are treated as they occur, with little emphasis on prevention. Fortunately, during the past years several longitudinal population-based studies have pointed out modifiable risk factors for dementia, many of them known for their association with cardiovascular disease.1 While it is important to count and manage all risk factors, an integrated, global risk assessment can provide a quantitative overview of the patients’ situation and help physicians and patients (on a clinical level) and general population (on a public health level) set goals and make decisions about necessary lifestyle-related changes or pharmacologic treatment, or both. Preventive cardiology is way ahead in this respect (i.e., Framingham risk scores). In this issue of Neurology ®, Dr. Barnes et al.2 present a late-life dementia risk index meant to stratify older adults into those with low, moderate, or high risk of …

Predicting risk of dementia in older adults

To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years. Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients. Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores. The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.

Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE Study

Caffeine stimulates central nervous system on a short term. However, the long-term impact of caffeine on cognition remains unclear. We aimed to study the association between coffee and/or tea consumption at midlife and dementia/Alzheimer's disease (AD) risk in late-life. Participants of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were randomly selected from the survivors of a population-based cohorts previously surveyed within the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or 1987 (midlife visit). After an average follow-up of 21 years, 1409 individuals (71%) aged 65 to 79 completed the re-examination in 1998. A total of 61 cases were identified as demented (48 with AD). Coffee drinkers at midlife had lower risk of dementia and AD later in life compared with those drinking no or only little coffee adjusted for demographic, lifestyle and vascular factors, apolipoprotein E epsilon4 allele and depressive symptoms. The lowest risk (65% decreased) was found in people who drank 3-5 cups per day. Tea drinking was relatively uncommon and was not associated with dementia/AD. Coffee drinking at midlife is associated with a decreased risk of dementia/AD later in life. This finding might open possibilities for prevention of dementia/AD.

Early parental death and late-life dementia risk: findings from the Cache County Study

SIR—Dementia is a major public health problem. Alzheimer's disease (AD) comprises the majority of dementia cases, and while the causes are still largely unknown, epidemiological studies are investigating a broad array of both genetic and environmental risk factors. Plausible aetiological mechanisms include lipid metabolism, inflammation and glucose regulation. Emerging biological evidence suggests that another potential mechanism for increased AD risk is neuronal death through the lifelong cumulative effect of stress reactivity and recovery [1]. Repeated stress causes damage to the CA3 region of the hippocampus via glucocorticoids and excitatory amino acid neurotransmitters released during and immediately after stress. Long-term, chronic stress over many years appears to continue the process and result in neuronal death in the hippocampus [2]. Physiological stress responses may also affect health by modulating the rate of cellular ageing via higher oxidative stress, lower telomerase activity and shorter telomere length, all indicators of cell longevity [3] with evidence that neurodegenerative changes may begin decades before clinical manifestation [4, 5]. These potential biological mechanisms, viewed from a lifecourse perspective, are consistent with observations that poor growth and development and adverse environmental conditions in early childhood are associated with increased disease risk in late life [6]. Socioeconomic adversity in the early years of life, specifically father's occupation of unskilled manual labourer, has been associated with a 2-fold increase in offspring AD risk [7] and faster rate of late-life cognitive decline in offspring [8]. Early-life parental death is an unexpected and traumatic event which usually poses the greatest adaptive challenges [9] thus introducing a host of potential stressors. These are not only economic but also psychosocial and may have a lifelong impact, especially for individuals with inadequate access to social and emotional resources. Though few studies directly address this question, in a sample of elderly Swedes, a 6-fold increase in dementia risk was demonstrated among participants experiencing a parental death before age 16 [10]. Although early-life adversity is not easily modifiable, establishing a clear link between psychosocial adversity and increased vulnerability to AD and other dementias will aid in the identification of at-risk individuals for more targeted interventions. Effective interventions may reduce the intensity of the body's physiological stress response and vulnerability to neurodegenerative diseases such as AD and other dementias. We report here analyses of the relationship between early parental death and dementia risk, in a large population-based epidemiological study. The relative effect of parental death at different stages in the lifecourse was examined. We hypothesised that experiencing early parental death would significantly increase dementia risk, with stronger effects posited for parental deaths occurring earlier in the course of development. Analyses were conducted before and after controlling for gender, age, education and apolipoprotein E (APOE) genotype.

P4-056: Work-life experience of psychosocial stress in relation to late-life risk of dementia and Alzheimer's disease

P4-056: Work-life experience of psychosocial stress in relation to late-life risk of dementia and Alzheimer's disease

O1-01-04: Midlife proficiency with written Japanese and late life dementia risk among Japanese-American men. The Honolulu-Asia aging study

was to investigate the possible effect modification of the apoE e4 allele for several lifestyle related risk factors for dementia and AD. Methods: Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 (73%) aged 65 to 79 years were reexamined in 1998. Results: The apoE e4 allele was an independent risk factor for dementia even after adjustments for lifestyle and vascular factors (OR 2.83, 95% CI 1.61-4.97). Physical inactivity, alcohol drinking, and smoking at midlife increased the risk of dementia and AD particularly among the apoE e4 carriers. Further, among the apoE e4 carriers low to moderate dietary intake of polyunsaturated fats at midlife, as well as moderate to high intake of saturated fats were associated with increased risk of dementia and AD. Also the summarized effect of the lifestyle related factors was more pronounced among the apoE e4 carriers. Conclusions: Physical inactivity, dietary fat intake, alcohol drinking, and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE e4 carriers. The apoE e4 carriers may be more vulnerable for various lifestyle related factors. Thus, especially the carriers of the apoE e4 allele might benefit from adopting a healthy and moderate lifestyle.

Loneliness and Risk of Alzheimer Disease

Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD). Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions. Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions. During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction. Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.

Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study

Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles. Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of beta coefficients and the dementia risk score was the sum of these individual scores (range 0-15). Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (> or = 47 years), low education (< 10 years), hypertension, hypercholesterolaemia, and obesity. The dementia risk score predicted dementia well (area under curve 0.77; 95% CI 0.71-0.83). The risk of dementia according to the categories of the dementia risk score was 1.0% for those with a score of 0-5, 1.9% for a score of 6-7, 4.2% for a score of 8-9, 7.4% for a score of 10-11, and 16.4% for a score of 12-15. When the cut-off of 9 points or more was applied the sensitivity was 0.77, the specificity was 0.63, and the negative predictive value was 0.98. The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.