Late-Life Risk Factors for All-Cause Dementia and Differential Dementia Diagnoses in Women: A Prospective Cohort Study.
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SUBMITTER: Neergaard JS
PROVIDER: S-EPMC4839938 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Depression prevention requires identifying key risk contributors. Prior studies have identified several factors related to late-life depression but have seldom addressed factors jointly or in dose-response fashion. This study aimed to examine a wide range of potential predisposing factors and to estimate individual and joint contributions to risk of late-life depression in women. A total of 21,728 women aged ≥65years, without prior depression, in the Nurses' Health Study conducted in the United States were followed from 2000 to 2010. Demographic, social, lifestyle/behavioral and health variables were selected a priori from the literature or previous findings in this cohort. Depression was defined as physician/clinician-diagnosed depression, regular antidepressant use, or the presence of severe depressive symptoms. During 10-year follow-up, 3945 incident cases were identified. After simultaneous multivariable-adjustment, multiple factors in the domains of social stress (lower self-rated societal position and high volume of caregiving to disabled/ill relatives), unfavorable lifestyle (smoking, physical inactivity, heavy or binge drinking), and poor physical health (multiple comorbidity burden, excessive sleep, difficulty falling/staying asleep, bodily pain, and physical/functional limitation or disability) were significantly associated with higher depression risk; many featured dose-response relationships. Sensitivity analyses that excluded outcomes within 2years yielded similar estimates. The total population attributable fraction for all factors was 55.5%. Physical/functional limitation accounted for one-quarter of population attributable fraction, followed by problematic sleep, inadequate exercise, and pain (combining for one-third of population attributable fraction). Efforts to remediate or prevent these factors may contribute to an efficient strategy for late-life depression prevention in women.
| S-EPMC5455056 | biostudies-literature
Project description:BackgroundDementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority.MethodsIn prospective study of 958 ambulant community-dwelling older women (≥70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records.FindingsAt baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation (n = 132) and/or death (n = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38-2.97; extensive, aHR 2.10 95%CI 1.33-3.32), compared to women with low AAC.InterpretationIn community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia.FundingKidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia.
| S-EPMC9535408 | biostudies-literature
Project description:IntroductionAlzheimer's disease and related dementias can be considered the epidemic of the 21st century. Particularly, the predicted growth in the size of elderly populations in low-income and middle-income countries is expected to produce a dramatic surge in dementia prevalence and incidence. Although a rising burden of dementia presents an urgent challenge for India, previous efforts to study dementia in the country have relied on non-representative samples in geographically restricted regions. The Harmonised Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) will provide rich, population-representative data on late-life cognition and dementia and their risk factors for the first time in India.MethodsThe LASI-DAD will recruit a sample of 3000 people aged 60+ years. Their family members or friends, whom respondents nominate as informants, participate in the computer-assisted personal interview. The study sample is drawn from the ongoing, nationally representative Longitudinal Aging Study in India, a multipurpose panel survey of aging. We aim to collect rich data on cognitive and neuropsychological tests, informant reports, and epidemiological data through a comprehensive geriatric assessment, and venous blood collection and assays. For a subsample, we collect neuroimaging data. Data collection is currently in progress in 14 States and Union Territories of India. Clinicians will provide clinical consensus diagnosis based on the Clinical Dementia Rating.Ethics and disseminationEthics approval was obtained from the Indian Council of Medical Research and all collaborating institutions. Anonymised data will be available for the larger research community through a secured website hosted by the Gateway to Global Aging Data platform. Research findings from the LASI-DAD team will be disseminated through journal publications and presentations at professional conferences.
| S-EPMC6677961 | biostudies-literature
Project description:BackgroundLiver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia.MethodsWe conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer's disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses.Results155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer's disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18-1.48]) but a reduced risk of Alzheimer's disease (0.92 [0.84-1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65-1.96]), vascular dementia (2.95 [2.53-3.45]) and Alzheimer's disease (1.46 [1.26-1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25-3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer's disease (0.83 [0.75-0.91]) and all-cause dementia (0.9 [0.84-0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1-1.39]) but not Alzheimer's disease (1.0 [0.91-1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer's disease were only present in those without MASLD (0.78 [0.67-0.91]).ConclusionsMAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.
| S-EPMC11201326 | biostudies-literature
Project description:Objective To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality.Design Longitudinal study with up to 32 years of follow-up.Setting Nurses' Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012).Participants 74 582 women from the Nurses' Health Study and 39 284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline.Main outcome measures Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drinking while outcome was mortality (all cause, cardiovascular, cancer). Cox proportional hazard models were used to calculate the adjusted hazard ratios of all cause, cancer, and cardiovascular mortality with their 95% confidence intervals across categories of BMI, with 22.5-24.9 as the reference.Results During up to 32 years of follow-up, there were 30 013 deaths (including 10 808 from cancer and 7189 from cardiovascular disease). In each of the four categories of BMI studied (18.5-22.4, 22.5-24.9, 25-29.9, ≥30), people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors.Conclusion Although people with a higher BMI can have lower risk of premature mortality if they also have at least one low risk lifestyle factor, the lowest risk of premature mortality is in people in the 18.5-22.4 BMI range with high score on the alternate healthy eating index, high level of physical activity, moderate alcohol drinking, and who do not smoke. It is important to consider diet and lifestyle factors in the evaluation of the association between BMI and mortality.
| S-EPMC5122318 | biostudies-literature
Project description:BackgroundAlthough cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women.Methods and findingsWe used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996-2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44-0.74) for total mortality, 0.29 (0.16-0.54) for CVD mortality, and 0.76 (0.54-1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4-5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths.ConclusionsIn this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern-including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake-was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention. Please see later in the article for the Editors' Summary.
| S-EPMC2939020 | biostudies-literature
Project description:ObjectivesDepression can be a prodromal feature or a risk factor for dementia. We aimed to investigate which clinical factors in patients with late-life depression are associated with a higher risk of developing dementia and a more rapid conversion.DesignRetrospective cohort study.SettingSouth London and Maudsley NHS Foundation Trust (SLaM) secondary mental healthcare services.ParticipantsThe SLaM Clinical Record Interactive Search was used to retrieve anonymised data on 3659 patients aged 65 years or older who had received a diagnosis of depression in mental health services and had been followed up for at least 3 months.Outcome measuresPredictors of development of incident dementia were investigated, including demographic factors, health status rated on the Health of the National Outcome scale for older people (HoNOS65+), depression recurrence and treatments including psychotropic drugs and cognitive behavioural therapy (CBT).ResultsIn total, 806 (22.0%) patients developed dementia over a mean follow-up time of 2.7 years. Significant predictors of receiving a dementia diagnosis in fully adjusted models and after accounting for multiple comparisons were older age (adjusted HR=1.04, 95% CI 1.03 to 1.06 per year difference from sample mean) and the HoNOS65+ subscale measuring cognitive problems (HR=4.72, 95% CI 3.67 to 6.06 for scores in the problematic range). Recurrent depressive disorder or past depression (HR=0.65, 95% CI 0.55 to 0.77) and the receipt of CBT (HR=0.73 95% CI 0.61 to 0.87) were associated with a lower dementia risk. Over time, hazards related to age increased and hazards related to cognitive problems decreased.ConclusionsIn older adults with depression, a higher risk of being subsequently diagnosed with dementia was predicted by higher age, new onset depression, severity of cognitive symptoms and not receiving CBT. Further exploration is needed to determine whether the latter risk factors are responsive to interventions.
| S-EPMC7252968 | biostudies-literature
Project description:There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ? APOE ?4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants.A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.
| S-EPMC5723557 | biostudies-literature
Project description:Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson's cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status. Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = -178.86 cm3, 95% CI = -325.07 to -32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95). Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.
| S-EPMC8719837 | biostudies-literature
Project description:Study questionAre there associations between natural or surgical menopause and incident dementia by age at menopause?Summary answerCompared to age at menopause of 46-50 years, earlier natural menopause (≤40 and 41-45 years) was related to higher risk of all-cause dementia, while a U-shape relationship was observed between age at surgical menopause and risk of dementia.What is known alreadyMenopause marks the end of female reproductive period. Age at menopause reflects the length of exposure to endogenous estrogen. Evidence on the association between age at natural, surgical menopause, and risk of dementia has been inconsistent.Study design, size, durationA population-based cohort study involving 160 080 women who participated in the UK Biobank study.Participants/materials, setting, methodsWomen with no dementia at baseline, and had no missing data on key exposure variables and covariates were included. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs on the association of categorical menopause age with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). Restricted cubic splines were used to model the non-linear relationship between continuous age at natural, surgical menopause, and risk of dementia. In addition, we analyzed the interaction effect of ever-used menopausal hormone therapy (MHT) at baseline, income level, leisure activities, and age at menopause on risk of dementia.Main results and the role of chanceCompared to women with age at menopause of 46-50 years, women with earlier natural menopause younger than 40 years (1.36, 1.01-1.83) and 41-45 years (1.19, 1.03-1.39) had a higher risk of all-cause dementia, while late natural menopause >55 years was linked to lower risk of dementia (0.83, 0.71-0.98). Compared to natural menopause, surgical menopause was associated with 10% higher risk of dementia (1.10, 0.98-1.24). A U-shape relationship was observed between surgical menopause and risk of dementia. Women with surgical menopause before age 40 years (1.94, 1.38-2.73) and after age 55 years (1.65, 1.21-2.24) were both linked to increased risk of all-cause dementia. Women with early natural menopause without ever taking MHT at baseline had an increased risk of AD. Also, in each categorized age at the menopause level, higher income level or higher number of leisure activities was linked to a lowers risk of dementia.Limitations, reasons for cautionMenopausal age was based on women's self-report, which might cause recall bias.Wider implication of the findingsWomen who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures to delay the development of dementia.Study funding/competing interestsThis work was supported by the Start-up Foundation for Scientific Research in Shandong University (202099000066), Science Fund Program for Excellent Young Scholars of Shandong Provence (Overseas) (2022HWYQ-030), and the National Natural Science Foundation of China (82273702). There are no competing interests.Trial registration numberN/A.
| S-EPMC10663050 | biostudies-literature