Mild cognitive impairment: epidemiology and dementia risk in an elderly Italian population

OBJECTIVES: To investigate prevalence and incidence of mild cognitive impairment (MCI) and its risk of progression to dementia in an elderly Italian population.
DESIGN: Longitudinal.
SETTING: Population-based cohort aged 65 and older resident in an Italian municipality.
PARTICIPANTS: A total of 1,016 subjects underwent baseline evaluation in 1999/2000. In 2003/04, information about cognitive outcome was collected for 745 participants who were free of dementia at baseline.
MEASUREMENTS: MCI (classified as with or without impairment of the memory domain), dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) diagnosed according to current international criteria.
RESULTS: Overall prevalence of MCI was 7.7% (95% confidence interval (CI)=6.1–9.7 %) and was greater with older age and poor education. During 4 years of follow-up, 155 incident MCI cases were diagnosed, with an incidence rate of 76.8 (95% CI=66.8–88.4) per 1,000 person-years. Approximately half of prevalent and incident MCI cases had memory impairment. Compared with normal cognition, multivariable-adjusted risk for progression from MCI with memory impairment to dementia was 4.78 (95% CI=2.78–8.07) for any dementia, 5.92 (95% CI=3.20–10.91) for AD, and 1.61 (95% CI=0.37–7.00) for VaD. No association with dementia risk was found for MCI without memory impairment. Approximately one-third of MCI cases with memory impairment did not progress to dementia.
CONCLUSION: MCI occurs often in this elderly Italian cohort and is associated with greater risk of AD, but only when the impairment involves the memory domain. However, a substantial proportion of MCI cases with memory impairment do not progress to dementia.     

Effect of Walking Distance on 8‐Year Incident Depressive Symptoms in Elderly Men with and without Chronic Disease: The Honolulu‐Asia Aging Study

OBJECTIVES: To determine the effect of walking on incident depressive symptoms in elderly Japanese‐American men with and without chronic disease. DESIGN: Prospective cohort study. SETTING: The Honolulu‐Asia Aging Study. PARTICIPANTS: Japanese‐American men aged 71 to 93 at baseline. MEASUREMENTS: Physical activity was assessed according to self‐reported distance walked per day. Depressive symptoms were measured using an 11‐question version of the Centers for Epidemiologic Studies Depression Scale (CES‐D 11) at the fourth examination (n=3,196) and at the seventh examination 8 years later (1999/00, n=1,417). Presence of incident depressive symptoms was defined as a CES‐D 11 score of 9 or greater or taking antidepressants at Examination 7. Subjects with prevalent depressive symptoms at baseline were excluded. RESULTS: Age‐adjusted 8‐year incident depressive symptoms were 13.6%, 7.6%, and 8.5% for low (<0.25 miles/day), intermediate (0.25–1.5 miles/day), and high (>1.5 miles/day) walking groups at baseline (P=0.008). Multiple logistic regression analyses, adjusted for age, education, marital status, cardiovascular risk factors, prevalent diseases, and functional impairment, showed that those in the intermediate and highest walking groups had significantly lower odds of developing 8‐year incident depressive symptoms (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.32–0.83, P=.006 and OR=0.61, 95% CI= 0.39–0.97, P=.04, respectively). Analysis found that this association was significant only in participants without chronic diseases (coronary heart disease, cerebrovascular accident, cancer, Parkinson's disease, dementia, or cognitive impairment) at baseline. CONCLUSION: Daily physical activity (≥0.25 mile/day) is significantly associated with lower risk of 8‐year incident depressive symptoms in elderly Japanese‐American men without chronic disease at baseline.     

Depressive symptoms, chronic diseases, and physical disabilities as predictors of cognitive functioning trajectories in older Americans

OBJECTIVES: To determine the concurrent influence of depressive symptoms, medical conditions, and disabilities in activities of daily living (ADLs) on rates of decline in cognitive function of older Americans. DESIGN: Prospective cohort. SETTING: National population based. PARTICIPANTS: A national sample of 6,476 adults born before 1924. MEASUREMENTS: Differences in cognitive function trajectories were determined according to prevalence and incidence of depressive symptoms, chronic diseases, and ADL disabilities. Cognitive performance was tested five times between 1993 and 2002 using a multifaceted inventory examined as a global measure (range 0–35, standard deviation (SD) 6.0) and word recall (range 0–20, SD 3.8) analyzed separately. RESULTS: Baseline prevalence of depressive symptoms, stroke, and ADL limitations were independently and strongly associated with lower baseline cognition scores but did not predict future cognitive decline. Each incident depressive symptom was independently associated with a 0.06‐point lower (95% confidence interval (CI)=0.02–0.10) recall score, incident stroke with a 0.59‐point lower total score (95% CI=0.20–0.98), each new basic ADL limitation with a 0.07‐point lower recall score (95% CI=0.01–0.14) and a 0.16‐point lower total score (95% CI=0.07–0.25), and each incident instrumental ADL limitation with a 0.20‐point lower recall score (95% CI=0.10–0.30) and a 0.52‐point lower total score (95% CI=0.37–0.67). CONCLUSION: Prevalent and incident depressive symptoms, stroke, and ADL disabilities contribute independently to poorer cognitive functioning in older Americans but do not appear to influence rates of future cognitive decline. Prevention, early identification, and aggressive treatment of these conditions may ameliorate the burdens of cognitive impairment.     

Physical Activity Over the Life Course and Its Association with Cognitive Performance and Impairment in Old Age

OBJECTIVE: To determine how physical activity at various ages over the life course is associated with cognitive impairment in late life. DESIGN: Cross‐sectional study. SETTING: Four U.S. sites. PARTICIPANTS: Nine thousand three hundred forty‐four women aged 65 and older (mean 71.6) who self‐reported teenage, age 30, age 50, and late‐life physical activity. MEASUREMENTS: Logistic regression was used to determine the association between physical activity status at each age and likelihood of cognitive impairment (modified Mini‐Mental State Examination (mMMSE) score >1.5 standard deviations below the mean, mMMSE score≤22). Models were adjusted for age, education, marital status, diabetes mellitus, hypertension, depressive symptoms, smoking, and body mass index. RESULTS: Women who reported being physically active had a lower prevalence of cognitive impairment in late life than women who were inactive at each time (teenage: 8.5% vs 16.7%, adjusted odds ratio (AOR)=0.65, 95% confidence interval (CI)=0.53–0.80; age 30: 8.9% vs 12.0%, AOR=0.80, 95% CI=0.67–0.96); age 50: 8.5% vs 13.1%, AOR=0.71, 95% CI=0.59–0.85; old age: 8.2% vs 15.9%, AOR=0.74, 95% CI=0.61–0.91). When the four times were analyzed together, teenage physical activity was most strongly associated with lower odds of late‐life cognitive impairment (OR=0.73, 95% CI=0.58–0.92). However, women who were physically inactive as teenagers and became active in later life had lower risk than those who remained inactive. CONCLUSIONS: Women who reported being physically active at any point over the life course, especially as teenagers, had a lower likelihood of cognitive impairment in late life. Interventions should promote physical activity early in life and throughout the life course.     

Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging

Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS–ADRDA criteria, and ICD-10 codes. Among 873 hypertension-treated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16–1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI, 0.39–8.37). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 –0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08–0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a “class” was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.     

Depressive Symptoms and Incident Cognitive Impairment in Cognitively Well-Functioning Older Men and Women

OBJECTIVES: To investigate whether the effect of depressive symptoms on the risk of cognitive decline and incident cognitive impairment (CI) in cognitively well-functioning older persons differed between men and women and whether sex differences in cerebrovascular factors might explain this.
DESIGN: Prospective cohort study.
SETTING: General community.
PARTICIPANTS: One thousand four hundred eighty-seven well-functioning Chinese older adults (Mini-Mental State Examination (MMSE) score ≥24) assessed at baseline for the presence of depressive symptoms (Geriatric Depression Scale score ≥5), and covariates (age, apolipoprotein E ɛ4, education, smoking, alcohol drinking, and vascular risk factors and diseases).
MAIN OUTCOME MEASURES: Incident CI and change in MMSE were assessed at 2-year follow-up.
RESULTS: In the whole sample, participants with depression showed significantly more incident CI than those without (5.7% vs 2.6%, P =.04; adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.05–5.00. Significantly higher OR was observed only in men (OR=4.75, 95% CI=1.22–18.5) and not for women (OR=1.29). There was a correspondingly greater rate of cognitive decline in participants with depressive symptoms that was observed to be marked only in men and not in women. The association was accentuated in subgroups with hypertension or vascular factors, but the sex differences in association were consistently observed.
CONCLUSION: The association between depressive symptoms and risk of cognitive decline was observed only in men and was not explained by sex differences in vascular factors. The comorbid presence of underlying cerebral vascular pathology or multi-infarct disease was possibly not a mediating factor but might amplify the process of cognitive decline.     

Associations between dementia/mild cognitive impairment and cognitive performance and activity levels in youth

OBJECTIVES: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth. DESIGN: Retrospective cohort study. SETTING: Research volunteers living throughout the United States. PARTICIPANTS: A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s. MEASUREMENTS: Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education. RESULTS: High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95% CI=0.12-0.84). No association was found between sex or education and adult cognitive status in this model. CONCLUSION: High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological "reserve," and involvement in activities may contribute to "reserve." Early neuropathology and ascertainment bias are also possible explanations for the observed associations.     

Depressive symptoms, inflammation, and ischemic stroke in older adults: a prospective analysis in the cardiovascular health study

OBJECTIVES: To investigate the mediator role of inflammation in any relationship between depressive symptoms and ischemic stroke.
DESIGN: Longitudinal prospective study.
SETTING: Review of medical records, death certificates, and the Medicare healthcare utilization database for hospitalizations.
PARTICIPANTS: Total of 5,525 elderly men and women aged 65 and older who were prospectively followed from 1989 to 2000 as participants in the Cardiovascular Health Study.
MEASUREMENTS: Depression symptom scores, inflammatory markers.
RESULTS: Greater depressive symptoms were associated with risk of ischemic stroke (unadjusted hazard ratio (HR)=1.32, 95% confidence interval (CI)=1.09–1.59; HR=1.26, 95% CI=1.03–1.54, adjusted for traditional risk factors). When a term for inflammation (C-reactive protein (CRP)) was introduced in the model, the HRs were not appreciably altered (unadjusted HR=1.31, 95% CI=1.08–1.58; adjusted HR=1.25, 95% CI=1.02–1.53), indicating that CRP at baseline was not a mediator in this relationship. In analyses stratified according to CRP levels, a J-shaped relationship between depressive symptoms and stroke was evident in the unadjusted analyses; in the fully adjusted model, only CRP in the highest tertile was associated with a higher risk for stroke in the presence of higher depressive symptoms scores.
CONCLUSION: The analyses from this prospective study provide evidence of a positive association between depressive symptoms and risk of incident stroke. Inflammation, as measured according to CRP at baseline, did not appear to mediate the relationship between depressive symptoms and stroke.     

Heart Failure and Incident Late‐Life Depression

OBJECTIVES: To assess whether heart failure (HF) increases the risk of developing depression and whether the use of loop diuretics in persons with HF alters this risk. DESIGN: Population‐based cohort study between 1993 and 2005. SETTING: Ommoord, a district of Rotterdam, the Netherlands. PARTICIPANTS: Five thousand ninety‐five older adults free of depression at baseline. MEASUREMENTS: Detailed information on HF and depression was collected during examination rounds and through continuous monitoring of medical and pharmaceutical records. HF was defined according to the criteria of the European Society of Cardiology. Depressive episodes were categorized as clinically relevant depressive symptoms and depressive syndromes, including major depressive disorders defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression. RESULTS: HF was associated with greater risk of depressive symptoms and syndromes (HR=1.41, 95% CI=1.03–1.94) and depressive syndromes only (HR=1.66, 95% CI=1.09–2.52). In participants with HF, the use of loop diuretics was associated with a lower risk of depressive symptoms and syndromes (HR=0.46, 95% CI=0.22–0.96) and depressive syndromes only (HR=0.41, 95% CI=0.16–1.00). CONCLUSION: HF is an independent risk factor for incident depression in elderly persons. Patient with HF require careful follow‐up to monitor and prevent the onset of depression. Effective treatment of the debilitating symptoms of HF may prevent depression.     

Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study

OBJECTIVES: To estimate the predictive relationship between depressive symptoms and 8-year dementia incidence in a large prospective community sample of French older adults and to compare the effect magnitude for men and women. DESIGN: Prospective population-based cohort with four interview waves and complete vital status ascertainment. SETTING: Urban and rural communities in the Aquitaine Region (Gironde and Dordogne), southwest France. PARTICIPANTS: Three thousand seven hundred seventy-seven adults aged 65 and older residing in noninstitutional settings at study baseline. MEASUREMENTS: Each participant was interviewed by a neuropsychologist and screened for dementia with the Mini-Mental State Examination, a cognitive test battery, and a standardized questionnaire designed to ascertain the presence of the criteria for dementia according to the Diagnostic and Statistical Manual for Mental Disorders, Third Edition, Revised (DSM-III-R). Dementia status and subtype were confirmed using neurological examination and categorized according to DSM-III-R criteria for dementia and the National Institute of Neurological Disorders and Stroke/Alzheimer's and Related Disorders Association criteria. The Hachinski score was calculated to specify the etiology: possible or probable Alzheimer's disease, vascular dementia, and other types of dementia. Depressive symptomatology was evaluated using the Center for Epidemiologic Studies-Depression scale. Statistical analyses were weighted to correct for attrition not due to mortality. RESULTS: Ninety-seven men (incidence rate: 14.4/1,000) and 183 women (Incidence rate: 19.0/1,000) developed dementia during 8 years of follow-up. Baseline prevalence of depressive symptomatology was 12.9% for men and 14.7% for women. Depressive symptoms increased risk of dementia at subsequent interview wave, but only for men (odds ratio (OR) (men) = 3.5, 95% confidence interval (CI) = 1.9-6.5; OR (women) = 1.2, 95% CI = 0.7-2.0, P-value for sex difference = 0.03). The hypothesis that vascular depression might explain the observed sex difference was studied, and it was found that risk was 50% higher for men with hypertension who were depressed than for normotensive men. For women, hypertension status did not modify the absence of an association. CONCLUSION: This study supports the hypothesis of a relationship between proximal depressive symptomatology and dementia in men, but distant depression did not increase dementia risk in this sample. The results suggest that depression in older men might reflect a form of vascular depression associated with cerebral vascular pathology or multiinfarct disease that may amplify the dementing or declining process, hence accelerating the onset of manifest symptoms of dementia.     

Cognitive impairment,depressive symptoms,and functional decline in older people

OBJECTIVES: Although cognitive impairment and depressive symptoms are associated with functional decline, it is not understood how these risk factors act together to affect the risk of functional decline. The purpose of this study is to determine the relative contributions of cognitive impairment and depressive symptoms on decline in activity of daily living (ADL) function over 2 years in an older cohort. DESIGN: Prospective cohort study. SETTING: A U.S. national prospective cohort study of older people, Asset and Health Dynamics in the Oldest Old. PARTICIPANTS: Five thousand six hundred ninety-seven participants (mean age 77, 64% women, 86% white) followed from 1993 to 1995. MEASUREMENTS: Cognitive impairment and depressive symptoms were defined as the poorest scores: 1.5 standard deviations below the mean on a cognitive scale or 1.5 standard deviations above the mean on validated depression scales. Risk of functional decline in participants with depressive symptoms, cognitive impairment, and both, compared with neither risk factor, were calculated and stratified by baseline dependence. Analyses were adjusted for demographics and comorbidity. RESULTS: Eight percent (n = 450) of subjects declined in ADL function. In participants who were independent in all ADLs at baseline, the relative risk (RR) of 2-year functional decline was 2.3 (95% confidence interval (CI) = 1.7-3.1) for participants with cognitive impairment, 1.9 (95% CI = 1.3-2.6) for participants with depressive symptoms, and 2.4 (95% CI = 1.4-3.7) for participants with cognitive impairment and depressive symptoms. In participants who were dependent in one or more ADLs at baseline, RR of 2-year functional decline was 1.9 (95% CI = 1.2-2.8) for participants with cognitive impairment, 0.6 (95% CI = 0.3-1.3) for participants with depressive symptoms, and 1.5 (95% CI = 0.8-2.6) for participants with cognitive impairment and depressive symptoms. CONCLUSIONS: In participants with no ADL dependence at baseline, cognitive impairment and depressive symptoms are risk factors for decline, but that, in participants with dependence in ADL at baseline, cognitive impairment, but not depressive symptoms, is a risk factor for additional decline.     

Physical Frailty Is Associated with Incident Mild Cognitive Impairment in Community‐Based Older Persons

OBJECTIVES: To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI). DESIGN: Prospective, observational cohort study. SETTING: Approximately 40 retirement communities across the Chicago metropolitan area. PARTICIPANTS: More than 750 older persons without cognitive impairment at baseline. MEASUREMENTS: Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition. RESULTS: During up to 12 years of annual follow‐up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one‐unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27–2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities). CONCLUSION: Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.     

Overweight and Obesity in Old Age Are Not Associated with Greater Dementia Risk

OBJECTIVES: To describe the association between body mass index (BMI) and dementia risk in older persons. DESIGN: Prospective population‐based study, with 8 years of follow‐up. SETTING: The municipality of Lieto, Finland, 1990/91 and 1998/99. PARTICIPANTS: Six hundred five men and women without dementia aged 65 to 92 at baseline (mean age 70.8). MEASUREMENTS: Weight and height were measured at baseline and at the 8‐year follow‐up. Dementia was clinically assessed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Eighty‐six persons were diagnosed with dementia. Cox regression analyses, adjusted for age, sex, education, cardiovascular diseases, smoking, and alcohol use, indicated that, for each unit increase in BMI score, the risk of dementia decreased 8% (hazard ratio (HR)=0.92, 95% confidence interval (CI)=0.87–0.97). This association remained significant when individuals who developed dementia early during the first 4 years of follow‐up were excluded from the analyses (HR=0.93, 95% CI=0.86–0.99). Women with high BMI scores had a lower dementia risk (HR=0.90, 95% CI=0.84–0.96). Men with high BMI scores also tended to have a lower dementia risk, although the association did not reach significance (HR=0.95, 95% CI=0.84–1.07). CONCLUSION: Older persons with higher BMI scores have less dementia risk than their counterparts with lower BMI scores. High BMI scores in late life should not necessarily be considered to be a risk factor for dementia.     

Interaction between body mass index and central adiposity and risk of incident cognitive impairment and dementia: results from the Women's Health Initiative Memory Study

OBJECTIVES: To assess the relationship between body mass index (BMI) and waist–hip ratio (WHR) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women's Health Initiative Memory Study (WHIMS). DESIGN: Prospective, randomized clinical trial of hormone therapies with annual cognitive assessments and anthropometrics. SETTING: Fourteen U.S. clinical sites of the WHIMS. PARTICIPANTS: Seven thousand one hundred sixty‐three postmenopausal women aged 65 to 80 without dementia. MEASUREMENTS: Annual cognitive assessments, average follow‐up of 4.4 years, including classification of incident cognitive impairment and probable dementia. Height, weight, waist, and hip measurements were assessed at baseline, and a waist–hip ratio (WHR) of 0.8 or greater was used as a marker of central adiposity. RESULTS: There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors. Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m² had a greater risk of cognitive impairment and probable dementia than more‐obese women or women with a WHR less than 0.80, although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m² had poorer scores on cognitive assessments. CONCLUSION: WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women. Underweight women (BMI<20.0 kg/m²) with a WHR less than 0.80 had a greater risk than those with higher BMIs. In normal‐weight to obese women (20.0–29.9 kg/m²), central adiposity (WHR≥0.80) is associated with greater risk of cognitive impairment and probable dementia than in women with higher BMI. These data suggest that central adiposity as a risk factor for cognitive impairment and probable dementia in normal‐weight women.     

Anxiety, depression, and 1-year incident cognitive impairment in community-dwelling older adults

OBJECTIVES: To examine in men and women the independent associations between anxiety and depression and 1‐year incident cognitive impairment and to examine the association of cognitive impairment, no dementia (CIND) and incident cognitive impairment with 1‐year incident anxiety or depression. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: Population‐based sample of 1,942 individuals aged 65 to 96. MEASUREMENTS: Two structured interviews 12 months apart evaluated anxiety and mood symptoms and disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Incident cognitive impairment was defined as no CIND at baseline and a follow‐up Mini‐Mental State Examination score at least 2 points below baseline and below the 15th percentile according to normative data. The associations between cognitive impairment and anxiety or depression were assessed using logistic regression adjusted for potential confounders. RESULTS: Incident cognitive impairment was, independently of depression, associated with baseline anxiety disorders in men (odds ratio (OR)=6.27, 95% confidence interval (CI)=1.39–28.29) and anxiety symptoms in women (OR=2.14, 95%=1.06–4.34). Moreover, the results indicated that depression disorders in men (OR=8.87, 95%=2.13–36.96) and anxiety symptoms in women (OR=4.31, 95%=1.74–10.67) were particularly linked to incident amnestic cognitive impairment, whereas anxiety disorders in men (OR=12.01, 95%=1.73–83.26) were especially associated with incident nonamnestic cognitive impairment. CIND at baseline and incident cognitive impairment were not associated with incident anxiety or depression. CONCLUSION: Anxiety and depression appear to have different relationships with incident cognitive impairment according to sex and the nature of cognitive impairment. Clinicians should pay particular attention to anxiety in older adults because it may shortly be followed by incident cognitive treatment.     

Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults

OBJECTIVES: To examine whether use of vitamins C or E alone or in combination was associated with lower incidence of dementia or Alzheimer's disease (AD).
DESIGN: Prospective cohort study.
SETTING: Group Health Cooperative, Seattle, Washington.
PARTICIPANTS: Two thousand nine hundred sixty-nine participants aged 65 and older without cognitive impairment at baseline in the Adult Changes in Thought study.
MEASUREMENTS: Participants were followed biennially to identify incident dementia and AD diagnosed according to standard criteria. Participants were considered to be users of vitamins C or E if they self-reported use for at least 1 week during the month before baseline.
RESULTS: Over a mean follow-up±standard deviation of 5.5±2.7 years, 405 subjects developed dementia (289 developed AD). The use of vitamin E was not associated with dementia (adjusted hazard ratio (HR)=0.98, 95% confidence interval (CI)=0.77–1.25) or with AD (HR=1.04; 95% CI=0.78–1.39). No association was found between vitamin C alone (dementia: HR=0.90, 95% CI=0.71–1.13; AD: HR=0.95, 95% CI=0.72–1.25) or concurrent use of vitamin C and E (dementia: HR=0.93, 95% CI=0.72–1.20; AD: HR=1.00, 95% CI=0.73–1.35) and either outcome.
CONCLUSION: In this study, the use of supplemental vitamin E and C, alone or in combination, did not reduce risk of AD or overall dementia over 5.5 years of follow-up.     

Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies

This study examined the association of diabetes with the onset of dementia (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to December 2010. All studies that examined the relationship between diabetes and the onset of dementia or MCI were included. Pooled relative risks were calculated using fixed and random effects models. Nineteen studies met our inclusion criteria for this meta-analysis, and 6184 subjects with diabetes and 38 530 subjects without diabetes were included respectively. All subjects were without dementia or MCI at baseline. The quantitative meta-analysis showed that subjects with diabetes had higher risk for AD (relative risk (RR):1.46, 95% confidence interval (CI): 1.20-1.77), VD (RR: 2.48, 95% CI: 2.08-2.96), any dementia (RR: 1.51, 95% CI: 1.31-1.74) and MCI (RR: 1.21, 95% CI: 1.02-1.45) than those without. The quantitative meta-analysis showed that diabetes was a risk factor for incident dementia (including AD, VD and any dementia) and MCI.     

Relationship Between Higher Estradiol Levels and 9-Year Mortality in Older Women: The Invecchiare in Chianti Study

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING: Community.
PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P =.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P =.04) and not predictive of death for less than 5 years ( P =.78).
CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.     

Depressive Symptoms in Middle Age and the Development of Later‐Life Functional Limitations: The Long‐Term Effect of Depressive Symptoms

OBJECTIVES: To determine whether middle‐aged persons with depressive symptoms are at higher risk for developing activity of daily living (ADL) and mobility limitations as they advance into older age than those without. DESIGN: Prospective cohort study. SETTING: The Health and Retirement Study (HRS), a nationally representative sample of people aged 50 to 61. PARTICIPANTS: Seven thousand two hundred seven community living participants in the 1992 wave of the HRS. MEASUREMENTS: Depressive symptoms were measured using the 11‐item Center for Epidemiologic Studies Depression Scale (CES‐D 11), with scores of 9 or more (out of 33) classified as significant depressive symptoms. Difficulty with five ADLs and basic mobility tasks (walking several blocks or up one flight of stairs) was measured every 2 years through 2006. The primary outcome was persistent difficulty with ADLs or mobility, defined as difficulty in two consecutive waves. RESULTS: Eight hundred eighty‐seven (12%) subjects scored 9 or higher on the CES‐D 11 and were classified as having significant depressive symptoms. Over 12 years of follow‐up, subjects with depressive symptoms were more likely to reach the primary outcome measure of persistent difficulty with mobility or difficulty with ADL function (45% vs 23%, Cox hazard ratio (HR)=2.33, 95% confidence interval (CI)=2.06–2.63). After adjusting for age, sex, measures of socioeconomic status, comorbid conditions, high body mass index, smoking, exercise, difficulty jogging 1 mile, and difficulty climbing several flights of stairs, the risk was attenuated but still statistically significant (Cox HR=1.44, 95% CI=1.25–1.66). CONCLUSION: Depressive symptoms independently predict the development of persistent limitations in ADLs and mobility as middle‐aged persons advance into later life. Middle‐aged persons with depressive symptoms may be at greater risk for losing their functional independence as they age.