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ABSTRACT: OBJECTIVES: Either dysphoria (sadness) or anhedonia (loss of interest in usually pleasurable activities) is required for a diagnosis of major depression. Although major depression is a known risk factor for disability in older persons, few studies have examined the relationship between the two core symptoms of major depression and disability or mortality. Our objective was to examine the relationship between these two core symptoms and time to disability or death. METHODS: In a longitudinal cohort study, we used the nationally representative Health and Retirement Study to examine this relationship in 11,353 persons older than 62 years (mean: 73 years) followed for up to 13 years. Dysphoria and anhedonia were assessed with the Short Form Composite International Diagnostic Interview. Our outcome measure was time to either death or increased disability, defined as the new need for help in a basic activity of daily living. We adjusted for a validated disability risk index and other confounders. RESULTS: Compared with subjects without either dysphoria or anhedonia, the risk for disability or death was not elevated in elders with dysphoria without anhedonia (adjusted hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.91-1.36). The risk was elevated in those with anhedonia without dysphoria (HR: 1.30; 95% CI: 1.06-1.60) and those with both anhedonia and dysphoria (HR: 1.28; 95% CI: 1.13-1.46). CONCLUSION: Our results highlight the need for clinicians to learn whether patients have lost interest in usually pleasurable activities, even if they deny sadness.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 04/2013; · 3.35 Impact Factor
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ABSTRACT: IMPORTANCE The prevalence of cognitive impairment and dementia are projected to rise dramatically during the next 40 years, and strategies for maintaining cognitive function with age are critically needed. Physical or mental activity alone result in relatively small, domain-specific improvements in cognitive function in older adults; combined interventions may have more global effects. OBJECTIVE To examine the combined effects of physical plus mental activity on cognitive function in older adults. DESIGN Randomized controlled trial with a factorial design. SETTING San Francisco, California. PARTICIPANTS A total of 126 inactive, community-residing older adults with cognitive complaints. INTERVENTIONS All participants engaged in home-based mental activity (1 h/d, 3 d/wk) plus class-based physical activity (1 h/d, 3 d/wk) for 12 weeks and were randomized to either mental activity intervention (MA-I; intensive computer) or mental activity control (MA-C; educational DVDs) plus exercise intervention (EX-I; aerobic) or exercise control (EX-C; stretching and toning); a 2 × 2 factorial design was used so that there were 4 groups: MA-I/EX-I, MA-I/EX-C, MA-C/EX-1, and MA-C/EX-C. MAIN OUTCOME MEASURES Global cognitive change based on a comprehensive neuropsychological test battery. RESULTS Participants had a mean age of 73.4 years; 62.7% were women, and 34.9% were Hispanic or nonwhite. There were no significant differences between the groups at baseline. Global cognitive scores improved significantly over time (mean, 0.16 SD; P < .001) but did not differ between groups in the comparison between MA-I and MA-C (ignoring exercise, P = .17), the comparison between EX-I and EX-C (ignoring mental activity, P = .74), or across all 4 randomization groups (P = .26). CONCLUSIONS AND RELEVANCE In inactive older adults with cognitive complaints, 12 weeks of physical plus mental activity was associated with significant improvements in global cognitive function with no evidence of difference between intervention and active control groups. These findings may reflect practice effects or may suggest that the amount of activity is more important than the type in this subject population. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00522899.
JAMA internal medicine. 04/2013;
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ABSTRACT: Purpose of Review: Epidemiologic studies can provide critical evidence to inform the timing and duration of nonpharmacologic interventions. Although more studies are needed to further determine long-term efficacy, the evidence supporting modifiable risk factors for prevention is compelling, and prevention strategies that incorporate multidomain nonpharmacologic factors may have the most impact.Recent Findings:Epidemiologic studies have identified a number of promising nonpharmacologic factors that have the potential to lower the risk of developing dementia.Summary:Potential modifiable strategies for dementia prevention include cardiovascular risk factors; lifestyle risk factors such as physical, cognitive, and social activity as well as nutrition, smoking, and alcohol use; and sleep quality. Results of randomized controlled trials for the treatment of cardiovascular risk factors have not been consistent, while interventions that increase physical, cognitive, and social activity have demonstrated protective effects for dementia risk. Trials of single-nutrient dietary supplementation have also been conflicting, but focus on multinutrient supplementation shows promise. Observational data also indicate that sleep quality may be a modifiable risk factor for dementia prevention.
Continuum (Minneapolis, Minn.). 04/2013; 19(2 Dementia):372-81.
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ABSTRACT: OBJECTIVES: Aging is associated with changes in circadian rhythms. Current evidence supports a role for circadian rhythms in the pathophysiology of depression. However, little is known about the relationship between depressive symptoms and circadian activity rhythms in older adults. We examined this association in community-dwelling older women. METHODS: We performed a cross-sectional analysis of 3,020 women (mean age: 83.55 ± 3.79 years) enrolled in the Study of Osteoporotic Fractures. Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as "normal" (0-2; referent group, N = 1,961), "some depressive symptoms" (3-5, N = 704), or "depressed" (≥6, N = 355). Circadian activity rhythm variables were measured using wrist actigraphy. RESULTS: In age-adjusted and Study of Osteoporotic Fractures site-adjusted models, greater levels of depressive symptoms were associated with decreased amplitude (height; df = 3,014, t = -11.31, p for linear trend <0.001), pseudo F-statistic (robustness; df = 3,014, t = -8.07, p for linear trend <0.001), and mesor (mean modeled activity; df = 3014, t = -10.36, p for linear trend <0.001) of circadian activity rhythms. Greater levels of depressive symptoms were also associated with increased odds of being in the lowest quartile for amplitude (df = 1, χ(2) = 9240, p for linear trend <0.001), pseudo F-statistic (df = 1, χ(2) = 49.73, p for linear trend <0.001), and mesor (df = 1, χ(2) = 81.12, p for linear trend <0.001). These associations remained significant in multivariate models. Post-hoc analyses comparing mean amplitude, mesor, and pseudo F-statistic values pair-wise between depression-level groups revealed significant differences between women with "some depressive symptoms" and the "normal" group. CONCLUSION: These data suggest a graded association between greater levels of depressive symptoms and more desynchronization of circadian activity rhythms in community-dwelling older women. This association was observed even for women endorsing subthreshold levels of depressive symptoms.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2013; · 3.35 Impact Factor
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ABSTRACT: OBJECTIVE
Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death.RESEARCH DESIGN AND METHODS
This study included 1,617 participants 60-98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models.RESULTSParticipants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 [95% CI 1.65-2.73] and 2.15 [1.58-2.95]) and dementia/CIND (2.48 [1.75-3.51]) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 [1.41-2.97] and 1.55 [0.93-2.58]) compared with those without diabetes.CONCLUSIONS
These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.
Diabetes care 03/2013; · 8.09 Impact Factor
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ABSTRACT: OBJECTIVE: To compare depressive symptoms between caregivers to persons with dementia and other illnesses and determine whether caregiver role captivity and care recipient disruptive behaviors mediate this association. METHODS: Prospective cohort study of older women in four U.S. communities followed from 1999 to 2009. Home-based interviews were used in 345 caregiving participants from the Caregiver-Study of Osteoporotic Fractures. Caregiver status was based on self-report of performing one or more instrumental or basic activities of daily living for a care recipient. Depressive symptoms were measured using the 20-item Center for Epidemiologic Studies Depression Scale. Scores of 16 or greater represented high depressive symptoms. Caregiver role captivity and care recipient problematic behaviors were measured using validated instruments. RESULTS: Approximately one third of the caregivers cared for a person with dementia. High depressive symptoms were more common among dementia caregivers (22.8% versus 11.2%, p <0.001) (unadjusted odds ratio: 2.12; 95% confidence interval [CI]: 1.20-3.74). This association was completely mediated by caregiver role captivity and care recipient problematic behaviors. In adjusted results, high depressive symptoms were associated with middle and highest tertiles of role captivity (adjusted odds ratios [AOR]: 5.01; 95% CI: 2.31-11.05 and AOR: 9.41; 95% CI: 3.95-22.40 for the middle and highest tertiles, respectively) and care recipient problematic behaviors (AOR: 2.52; 95% CI: 1.02-6.19 and AOR: 5.26; 95% CI: 2.00-13.8 for the middle and highest tertiles, respectively). CONCLUSION: Older caregivers to persons with dementia are at increased risk of high depressive symptoms. Targeting problematic behaviors among dementia patients and addressing aspects of dementia care that result in role captivity may ameliorate caregiver depression.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2013; · 3.35 Impact Factor
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ABSTRACT: To investigate the relationship between periodontal disease and cognitive decline.
Analysis of a prospective cohort study.
The Health, Aging and Body Composition (Health ABC) Study.
One thousand fifty-three participants who were administered the Modified Mini-Mental State Examination (3MS) at Year 1 (baseline) and Year 3 and had participated in a comprehensive periodontal examination at Year 2.
The prospective association between a range of oral health parameters and cognitive function was examined. Decline in 3MS score from Year 3 to 5 was investigated in 947 (89.9%) participants. Covariates included age, sex, education, race, cardiovascular disease and risk, and depressive symptoms.
Most indicators of adverse oral health at Year 2 were associated with cognitive impairment based on averaged 3MS scores less than 80 for Years 1 and 3, but education and race substantially confounded these associations. Higher gingival index, a measure of gingival inflammation, at Year 2 remained independently associated with this definition of cognitive impairment and, in fully adjusted analyses, was also an independent predictor of a more-than-5-point cognitive decline from Year 3 to 5.
Periodontitis may be a risk factor for cognitive decline. Gingivitis is reversible, and periodontitis to some degree is preventable and controllable when manifest. Therefore, further research is needed to clarify potential underlying mechanisms and oral health interventions that might ameliorate cognitive decline.
Journal of the American Geriatrics Society 02/2013; 61(2):177-84. · 3.74 Impact Factor
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ABSTRACT: BACKGROUND Whether hearing loss is independently associated with accelerated cognitive decline in older adults is unknown. METHODS We studied 1984 older adults (mean age, 77.4 years) enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998. Our baseline cohort consisted of participants without prevalent cognitive impairment (Modified Mini-Mental State Examination [3MS] score, ≥80) who underwent audiometric testing in year 5. Participants were followed up for 6 years. Hearing was defined at baseline using a pure-tone average of thresholds at 0.5 to 4 kHz in the better-hearing ear. Cognitive testing was performed in years 5, 8, 10, and 11 and consisted of the 3MS (measuring global function) and the Digit Symbol Substitution test (measuring executive function). Incident cognitive impairment was defined as a 3MS score of less than 80 or a decline in 3MS score of more than 5 points from baseline. Mixed-effects regression and Cox proportional hazards regression models were adjusted for demographic and cardiovascular risk factors. RESULTS In total, 1162 individuals with baseline hearing loss (pure-tone average >25 dB) had annual rates of decline in 3MS and Digit Symbol Substitution test scores that were 41% and 32% greater, respectively, than those among individuals with normal hearing. On the 3MS, the annual score changes were -0.65 (95% CI, -0.73 to -0.56) vs -0.46 (95% CI, -0.55 to -0.36) points per year (P = .004). On the Digit Symbol Substitution test, the annual score changes were -0.83 (95% CI, -0.94 to -0.73) vs -0.63 (95% CI, -0.75 to -0.51) points per year (P = .02). Compared to those with normal hearing, individuals with hearing loss at baseline had a 24% (hazard ratio, 1.24; 95% CI, 1.05-1.48) increased risk for incident cognitive impairment. Rates of cognitive decline and the risk for incident cognitive impairment were linearly associated with the severity of an individual's baseline hearing loss. CONCLUSIONS Hearing loss is independently associated with accelerated cognitive decline and incident cognitive impairment in community-dwelling older adults. Further studies are needed to investigate what the mechanistic basis of this association is and whether hearing rehabilitative interventions could affect cognitive decline.
JAMA internal medicine. 01/2013;
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ABSTRACT: OBJECTIVES: To determine which older adults tend to receive potentially inappropriate medications (PIMs), how this may differ according to cognitive status, and how the trajectories of PIM use change over time. DESIGN: Ten-year longitudinal cohort study. SETTING: Three clinical sites in the United States. PARTICIPANTS: One thousand four hundred eighty-four community-dwelling women aged 75 and older. MEASUREMENTS: At follow-up, cognitive status was ascertained and classified as normal, mild cognitive impairment (MCI), or dementia. Beers 2003 criteria and other literature were used to identify PIMs from detailed medication inventory performed at three time points. Anticholinergic load was measured using the Anticholinergic Cognitive Burden Scale (ACB), which assigns medications a value from 0 to 3 depending on anticholinergic properties. RESULTS: At baseline, 23.9% of women were taking at least one PIM and the mean ± SD ACB score was 1.41 ± 1.69. The most frequently reported PIMs were anticholinergics (15.2%), benzodiazepines (8.6%), and antispasmodics (8.0%). Over 10 years, PIM use increased for women with dementia (24.9-33.1%; P = .02) but remained fairly constant for women with MCI (23.9-23.0%; P = .84) and normal cognitive status (22.2-19.8%; P = .17). Mean ACB score increased significantly (P < .001) over time for all groups (dementia: 1.28-2.05; MCI: 0.98-1.66; normal: 0.99-1.48). CONCLUSION: PIM use and anticholinergic load in a community-dwelling population of older women was high, especially in women who later developed dementia. Future guidelines should limit PIM use and seek safer alternatives.
Journal of the American Geriatrics Society 01/2013; · 3.74 Impact Factor
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ABSTRACT: BACKGROUND AND PURPOSE: Arterial stiffness is a measure of subclinical cardiovascular disease and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults. METHODS: A total of 2488 subjects with baseline measure of arterial stiffness (mean age, 74.2 years; 52.3% women) were prospectively followed over 9 years in the Health, Aging, and Body Composition Study. Arterial stiffness was measured as pulse wave velocity (PWV) and analyzed in tertiles. Cognitive function was assessed using the Modified Mini-Mental State examination at baseline and repeated at years 3, 5, 8, and 10. Lower Modified Mini-Mental State examination scores indicate worse function. We fit linear mixed models to examine longitudinal changes in cognitive function over the 9 years of follow-up and logistic regression models, restricted to 1331 participants, to examine cognitive impairment defined as a decrease of ≥5 points after 9 years. We adjusted for sociodemographics, Apoe4, and cardiovascular disease risk factors. RESULTS: The annual decrease in Modified Mini-Mental State examination scores was 0.30 points at low PWV (95% confidence interval [CI], -0.37 to -0.22), 0.46 points at middle PWV (95% CI, -0.54 to -0.39), and 0.45 points at high PWV (95% CI, -0.53 to -0.38), from fully adjusted linear mixed models. In fully adjusted models, the odds of cognitive impairment after 9 years of follow-up was 40% greater for subjects with middle PWV (odds ratio [OR], 1.40; 95% CI, 1.03-1.92) and 59% greater for subjects with high PWV (OR, 1.59; 95% CI, 1.16-2.18), compared with low PWV. CONCLUSIONS: High arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline.
Stroke 01/2013; · 5.73 Impact Factor
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Kristine Yaffe,
Lynn Ackerson,
Tina D Hoang,
Alan S Go,
Maureen G Maguire,
Gui-Shuang Ying,
Ebenezer Daniel,
Lydia A Bazzano,
Martha Coleman,
Debbie L Cohen,
John W Kusek,
Akinlolu Ojo,
Stephen Seliger,
Dawei Xie,
Juan E Grunwald
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ABSTRACT: BACKGROUND: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTOR: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. OUTCOMES: Neuropsychological battery of 6 cognitive tests. MEASUREMENTS: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. RESULTS: The mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. LIMITATIONS: Unknown temporal relationship between retinopathy and impairment. CONCLUSIONS: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.
American Journal of Kidney Diseases 12/2012; · 5.43 Impact Factor
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ABSTRACT: OBJECTIVES
To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes.RESEARCH DESIGN AND METHODSMRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROI. Models were adjusted for age, race, and sex; GMV values for ROI were also adjusted for total brain volume (TBV).RESULTSIn multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMH. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007 left; P = 0.002 right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results.CONCLUSIONS
In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.
Diabetes care 11/2012; · 8.09 Impact Factor
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Amy L Byers,
Eric Vittinghoff,
Li-Yung Lui,
Tina Hoang,
Dan G Blazer,
Kenneth E Covinsky,
Kristine E Ensrud,
Jane A Cauley,
Teresa A Hillier,
Lisa Fredman, Kristine Yaffe
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ABSTRACT: CONTEXT Despite the frequent occurrence of depressive symptoms among older adults, especially women, little is known about the long-term course of late-life depressive symptoms. OBJECTIVE To characterize the natural course of depressive symptoms among older women (from the young old to the oldest old) followed up for almost 20 years. DESIGN Using latent-class growth-curve analysis, we analyzed women enrolled in an ongoing prospective cohort study (1988 through 2009). SETTING Clinic sites in Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley near Pittsburgh, Pennsylvania; and Portland, Oregon. PARTICIPANTS We studied 7240 community-dwelling women 65 years or older. MAIN OUTCOME MEASURE The Geriatric Depression Scale short form (score range, 0-15) was used to routinely assess depressive symptoms during the follow-up period. RESULTS Among older women, we identified 4 latent classes during 20 years, with the predicted probabilities of group membership totaling 27.8% with minimal depressive symptoms, 54.0% with persistently low depressive symptoms, 14.8% with increasing depressive symptoms, and 3.4% with persistently high depressive symptoms. In an adjusted model for latent class membership, odds ratios (ORs) for belonging in the increasing depressive symptoms and persistently high depressive symptoms classes, respectively, compared with a group having minimal depressive symptoms were substantially and significantly (P < .05) elevated for the following variables: baseline smoking (ORs, 4.69 and 7.97), physical inactivity (ORs, 2.11 and 2.78), small social network (ORs, 3.24 and 6.75), physical impairment (ORs, 8.11 and 16.43), myocardial infarction (ORs, 2.09 and 2.41), diabetes mellitus (ORs, 2.98 and 3.03), and obesity (ORs, 1.86 and 2.90). CONCLUSIONS During 20 years, almost 20% of older women experienced persistently high depressive symptoms or increasing depressive symptoms. In addition, these women had more comorbidities, physical impairment, and negative lifestyle factors at baseline. These associations support the need for intervention and prevention strategies to reduce depressive symptoms into the oldest-old years.
Archives of general psychiatry 10/2012; 69(10):1073-9. · 12.26 Impact Factor
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ABSTRACT: BACKGROUND: Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD). METHODS: The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. RESULTS: Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). CONCLUSIONS: An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2012; · 4.60 Impact Factor
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ABSTRACT: BACKGROUND: The association between obesity and dementia has been inconsistent, possibly due to changes in body composition often seen in old age. Leptin may be associated with better cognitive function. However, neuroprotection may be inhibited among obese subjects possibly due to leptin resistance. We sought to determine (i) if leptin is associated with risk of dementia or mild cognitive impairment (MCI) in a cohort of very old women, (ii) if this association is modified by obesity, and (iii) if leptin is a stronger risk factor compared with traditional anthropometric measures. METHODS: We studied 579 older women (mean age 82.6 years) from the ongoing prospective cohort Study of Osteoporotic Fractures, who were dementia-free at year-16 examination (our study baseline). Leptin (ng/mL) was measured using year-16 frozen serum, and anthropometric measures were collected during the same visit. Diagnosis of dementia/MCI was determined at year-20 examination. RESULTS: There was evidence for a multiplicative interaction between log leptin and categorical body mass index (p = .03). Among women with body mass index <25kg/m(2) (n = 190), 1SD difference in log leptin (0.91ng/mL) was associated with 32% lower odds of dementia/MCI (OR = .68; 95% CI = .46, .99), after adjustment. The association was not significant among women with body mass index ≥25kg/m(2) (n = 377). Traditional anthropometric measures such as weight, height, and body mass index were not associated with dementia/MCI. CONCLUSIONS: In this cohort of very old women, higher serum leptin was prospectively associated with lower odds of dementia/MCI in women with normal body mass index, but not in overweight or obese women. Leptin may be a better predictor of dementia/MCI than traditional anthropometric measures.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2012; · 4.60 Impact Factor
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ABSTRACT: Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association.
We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT).
For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference.
Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function.
Dementia and Geriatric Cognitive Disorders 07/2012; 33(6):400-9. · 2.14 Impact Factor
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Gregory J Tranah,
Michael A Nalls,
Shana M Katzman,
Jennifer S Yokoyama,
Ernest T Lam,
Yiqiang Zhao,
Sean Mooney,
Fridtjof Thomas,
Anne B Newman,
Yongmei Liu,
Steven R Cummings,
Tamara B Harris, Kristine Yaffe
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ABSTRACT: Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increased neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia (OR = 1.86, 95% CI = 1.23, 2.82, p = 0.0008) and haplogroup J participants experienced a statistically significant 8-year decline in 3MS (β = -0.14, 95% CI = -0.27, -0.03, p = 0.0006), both compared with common haplogroup H. The m.15244A>G, p.G166G, CytB variant was associated with a significant decline in DSST score (β = -0.58, 95% CI -0.89, -0.28, p = 0.00019) and the m.14178T>C, p.I166V, ND6 variant was associated with a significant decline in 3MS score (β = -0.87, 95% CI -1.31, -3.86, p = 0.00012). Finally, we sequenced the complete ~16.5 kb mtDNA from 135 Health ABC participants and identified several highly conserved and potentially functional nonsynonymous variants unique to 22 dementia cases and aggregate sequence variation across the hypervariable 2-3 regions that influences 3MS and DSST scores.
Journal of Alzheimer's disease: JAD 07/2012; 32(2):357-72. · 3.74 Impact Factor
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ABSTRACT: Plasma amyloid β-42 (Aβ42) and Aβ42/Aβ40 are increasingly recognized as biomarkers for dementia, with low levels indicating increased risk. Little is known about the demographic and medical correlates of plasma Aβ40 or Aβ42. In 997 community-dwelling, nondemented older adults from the Health, Aging, and Body Composition Study, we determined the cross-sectional association between a wide range of demographic and medical variables with Aβ40 and Aβ42. In multivariate stepwise linear regression models, Aβ40 was significantly associated with race (β=-14.70, F=22.01, P<0.0001), age (β=1.34, F=6.39, P=0.01), creatinine (β=52.91, F=151.77, P<0.0001), and the serum brain-derived neurotrophic factor (β=-0.0004, F=7.34, P=0.007); Aβ42 was significantly associated with race (β=-3.72, F=30.83, P<0.0001), sex (β=1.39, F=4.32, P=0.04), education (β=1.50, F=4.78, P=0.03), apolipoprotein E e4 genotype (β=-2.82, F=16.57, P<0.0001), and creatinine (β=9.32, F=120.09, P<0.0001). These correlates should be considered as potential confounders in future studies investigating plasma Aβ as a biomarker of dementia. Understanding fully how these correlates mediate or modify the association between plasma Aβ and dementia will be a fundamental step in determining the biological pathways through which plasma Aβ40 and Aβ42 are associated with dementia, and in determining their full potential as biomarkers.
Alzheimer disease and associated disorders 06/2012; · 2.88 Impact Factor
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Kristine Yaffe,
Cherie Falvey,
Nathan Hamilton,
Ann V Schwartz,
Eleanor M Simonsick,
Suzanne Satterfield,
Jane A Cauley,
Caterina Rosano,
Lenore J Launer,
Elsa S Strotmeyer,
Tamara B Harris
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ABSTRACT: OBJECTIVES To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance. DESIGN Prospective cohort study. SETTING Health, Aging, and Body Composition Study at 2 community clinics. PARTICIPANTS A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female). MAIN OUTCOME MEASURES Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A1c level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood. RESULTS At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incident DM during follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM (3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t = 6.09; P = .001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: -6.0- vs -4.5-point decline; t = 2.66; P = .008; DSST: -7.9- vs -5.7-point decline; t = 3.69; P = .001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F = 8.2; P for overall = .003; DSST: F = 3.4; P for overall = .04), even after multivariate adjustment. CONCLUSION Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.
Archives of neurology 06/2012; 69(9):1170-5. · 6.31 Impact Factor
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ABSTRACT: To determine the association between objectively measured sleep and subsequent placement in a nursing home or a personal care home.
Prospective cohort.
Participants' homes and sites of the Study of Osteoporotic Fractures.
One thousand six hundred sixty-four community-dwelling women with a mean age of 83 ± 4.
At baseline, participants completed an average of 4 nights of wrist actigraphy; they provided data on place of residence at baseline and at follow-up, 5 years later.
At baseline, participants had a mean total sleep time of 408 ± 72 minutes, mean wake after sleep onset of 71 ± 43 minutes, and mean sleep efficiency of 79 ± 11%. At follow-up, 71 (4%) were residing in a nursing home, and 127 (8%) were in a personal care home. Women with the most wake after sleep onset (by quartile) had more than twice the odds as those with the least of placement in a nursing home (adjusted odds ratio (AOR) = 2.94, 95% confidence interval (CI) = 1.34-6.44) or a personal care home (AOR = 2.33, 95% CI = 1.26-4.30). Similarly, women with the lowest sleep efficiency had more than three times the odds as those with the highest of nursing home placement (AOR = 3.25, 95% CI = 1.35, 7.82) and more than twice the odds of placement in a personal care home (AOR = 2.38, 95% CI = 1.33, 4.24). There was no association between sleep duration and placement.
In very old community-dwelling women, greater wake after sleep onset and lower sleep efficiency are risk factors for placement in a nursing home or personal care home. Sleep duration alone does not appear to increase the risk of placement in these long-term care settings.
Journal of the American Geriatrics Society 06/2012; 60(7):1237-43. · 3.74 Impact Factor
