To evaluate associations between mid- and late-life obesity and risk of dementia.
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
2,798 adults without dementia, mean age 74.7 years, 59.1% women, participating in the Cardiovascular Health Cognition Study completing a magnetic resonance image, measured for height and weight at baseline (late-life) and self-reporting weight at age 50 (mid-life). Body mass index (BMI) was calculated at both times.
Main Outcome Measures
Dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) classified by a multidisciplinary committee using standardized criteria.
Classification resulted in 480 persons with incident dementia, 245 with AD (no VaD) and 213 with VaD (with or without AD). In evaluations of mid-life obesity, an increased risk of dementia was found for obese (BMI >30) compared to normal (BMI 20-25) persons adjusted for demographics (HR: 1.39, 95% CI: 1.03-1.87) and for caradiovascularl risk factors (HR: 1.36, 95% CI: 0.94-1.95). The risk estimates reversed in assessments of late-life BMI. Underweight persons (BMI < 20) had an increased risk of dementia (HR: 1.62, 95% CI: 1.02-2.64) while being overweight (BMI 25-30) was not associated (HR: 0.92, 95% CI: 0.72-1.18) and being obese reduced the risk of dementia (HR: 0.63, 95% CI: 0.44-0.91) compared to those with normal BMI.
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
Dementia prevalence and its burden on families are increasing. Caregivers of persons with dementia have more depression and stress than the general population. Several interventions have proven efficacy in decreasing depression and stress in selected populations of caregivers. Hispanics in New York City tend to have a higher burden of dementia caregiving compared to non-Hispanic whites (NHW) because Hispanics have a higher prevalence of dementia, tend to have high family involvement, and tend to have higher psychosocial and economic stressors. Thus, we chose to test the effectiveness of a dementia caregiving intervention, the New York University Caregiver Intervention (NYUCI), with demonstrated efficacy in spouse caregivers in Hispanic relative caregivers of persons with dementia. Including the community health worker (CHW) intervention in both arms alleviates general psychosocial stressors and allows the assessment of the effectiveness of the intervention. Compared to two original efficacy studies of the NYUCI, which included only spouse caregivers, our study includes all relative caregivers, including common law spouses, children, siblings, a nephew and nieces. This study will be the first randomised trial to test the effectiveness of the NYUCI in Hispanic caregivers including non-spouses.
Methods and analysis
The design of the study is a randomised controlled trial (RCT). Participants are randomised to two arms: case management by a CHW and an intervention arm including the NYUCI in addition to case management by the CHW. The duration of intervention is 6 months. The main outcomes in the trial are changes in the Geriatric Depression Scale (GDS) and the Zarit Caregiver Burden Scale (ZCBS) from baseline to 6 months.
Ethics and dissemination
This trial is approved by the Columbia University Medical Center Institutional Review Board (AAAI0022), and funded by the National Institute on Minority Health and Health Disparities. The funding agency has no role in dissemination.
White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve.
Neurologically healthy older adults (n=717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively.
Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume.
For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition.
White matter hyperintensities; cognitive reserve; MRI; cognition
We explored whether ethnic differences in type 2 diabetes (T2D) explain ethnic disparities in cognitive impairment.
A cohort study of multiethnic community dwelling elderly persons in Northern Manhattan, New York.
941 participants aged ≥ 65 years without prevalent cognitive impairment or dementia (CID) were followed for a median of 7.1 years.
Main Outcomes Measures
CID was defined by a clinical dementia rating ≥ 0.5. CID risk attributable to T2D was estimated for each ethnic group using the hazard ratio (HR) relating T2D and CID and the ethnic prevalence of T2D.
448 participants developed CID (69 (31.4%) Non-Hispanic Whites (Whites), 152 (48.6%) Non-Hispanic-Blacks (Blacks), 227 (55.6%) Hispanics, p<0.001). T2D prevalence was 8.2% in Whites, 20.1% in Blacks, and 19.6 % in Hispanics, p<0.001. Controlling for age, gender, education, and APOEε4, the HR relating T2D and CID was 1.63 (95% CI 1.26, 2.09). CID attributable to T2D was higher in Blacks and Hispanics compared to Whites (11.4% vs. 4.9%; p=0.06). We estimated that reducing the ethnic disparities in diabetes prevalence could reduce the CID ethnic disparities by 17%.
Reducing ethnic differences in T2D prevalence could partially reduce ethnic differences in incident CID.
Type 2 diabetes; disparities; cognitive impairment; dementia
This manuscript provides a brief review of current concepts in the mechanisms potentially linking type-2-diabetes (T2D) with cognitive impairment. Existing epidemiologic studies, imaging studies, autopsy studies and clinical trials provide insights into the mechanisms linking T2D and cognitive impairment. There seems to be little dispute that T2D can cause cerebrovascular disease and thus cause vascular cognitive impairment (VCI). Whether T2D can cause late onset Alzheimer’s disease (LOAD) remains to be elucidated. Many epidemiologic studies show an association between T2D and cognitive impairment, but the association with VCI seems to be stronger compared to LOAD, suggesting that cerebrovascular disease may be the main mechanism linking T2D and cognitive impairment. Imaging studies show an association between T2D and imaging markers of LOAD, but these observations could still be explained by cerebrovascular mechanisms. Autopsy studies are few and conflicting, with some suggesting a predominantly cerebrovascular mechanism, and others providing support for a neurodegenerative mechanism. Thus far, the evidence from clinical trials is mixed in supporting a causal association between T2D and cognitive impairment, and most clinical trials that can answer this question are yet to be reported or finished. Given the epidemic of T2D in the world, it is important to elucidate whether the association between T2D and cognitive impairment, particularly LOAD, is causal, and if so, what are the mechanisms.
Type 2 diabetes; mechanisms; dementia; late onset Alzheimer’s disease; vascular cognitive impairment
To examine whether late-life depression, including depressive symptoms and antidepressant use, was associated with smaller total brain volume, smaller hippocampal volume, and larger white matter hyperintensity volume in a large community-based cohort of old persons without dementia.
Within the Washington/Hamilton Height-Inwood Columbia Aging Project (WHICAP), a community-based cohort study in northern Manhattan, 630 persons without dementia (mean age 80 years, SD=5) had volumetric measures of the total brain, hippocampus, and white matter hyperintensities (WMH) at 1.5Tesla MRI and data on current depression, defined as a score of 4 or higher on the 10-item CES-D or use of antidepressants.
Multiple linear regression analyses adjusted for age, sex, ethnicity, education, cardiovascular disease history, and MRI parameters showed that subjects with current depression had smaller relative total brain volume (B=−0.86%; 95%CI −1.68 to −0.05%; p<0.05), smaller relative hippocampal volume (B=−0.07 ml; 95%CI −0.14 to 0.00 ml; p=0.05), and larger relative WMH volume (natural logtransformed B=0.19 ml; 95%CI 0.02 to 0.35 ml; p<0.05). When examined separately, antidepressant use was significantly associated with smaller total brain, smaller hippocampal, and larger WMH volume, while high CES-D scores were not significantly associated with any of the brain measures, although the direction of association was similar as for antidepressant use.
With the caveat that analyses were cross-sectional and we had no formal diagnosis of depression, our findings suggest that in this community-based sample of old persons without dementia, late-life depression is associated with more brain atrophy and more white matter lesions, which was mainly driven by antidepressant use.
brain; hippocampus; white matter hyperintensity; depressive symptoms; antidepressants; elderly; population-based; cohort; MRI
Cerebrovascular disease is 1 of the possible mechanisms of the previously reported relationship between Mediterranean-type diet (MeDi) and Alzheimer’s disease (AD). We sought to investigate the association between MeDi and MRI infarcts.
High-resolution structural MRI was collected on 707 elderly 65 years or older community residents of New York with available dietary assessments administered an average of 5.8 years (3.22 standard deviations [SDs]) before the MRI. Participants were divided into 3 groups of adherence to MeDi (low, middle, and high tertiles). We examined the association of increasing adherence to MeDi with presence of infarcts on MRI. Models were run without adjustment, adjusted for basic demographic and clinical factors, and adjusted for vascular risk factors.
A total of 222 participants had at least 1 infarct. In the unadjusted model, compared to the low adherence group, those in the moderate MeDi adherence group had a 22% reduced odds of having an infarct (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.55–1.14), while participants in the highest MeDi adherence group had a 36% reduced odds (OR, 0.64; 95% CI, 0.42–0.97; p for trend = 0.04). In adjusted models, the association between MeDi adherence and MRI infarcts remained essentially unchanged. The association of high MeDi adherence with infarcts was comparable to that of hypertension (40% reduced probability), did not vary by infarct size or after excluding patients with dementia (n = 46) or clinical strokes (n = 86). There was no association between MeDi and white matter hyperintensities.
Higher adherence to the MeDi is associated with reduced cerebrovascular disease burden.
This manuscript provides a brief review of the epidemiologic evidence linking type 2 diabetes (T2D) and its precursor conditions, elevated adiposity and hyperinsulinemia, to dementia. Elevated adiposity in middle age is related to a higher risk of dementia but the data on this association in old age is conflicting. Hyperinsulinemia, a consequence of higher adiposity and insulin resistance is also related to a higher risk of dementia, including late onset Alzheimer’s disease (LOAD). Studies have consistently shown a relation of T2D with higher dementia risk, but the associations are stronger for vascular dementia compared to LOAD. One implication of these associations is that strategies used to prevent T2D can be used to prevent dementia. Several studies in the prevention and treatment of T2D are currently measuring cognitive outcomes and will provide information on whether T2D treatment and prevention can prevent cognitive decline and dementia.
adiposity; overweight; obesity; hyperinsulinemia; insulin; glucose; type 2 diabetes; alzheimer’s disease; vascular dementia
To determine whether pre-diagnosis vascular risk factors are associated with Alzheimer’s disease progression.
Inception cohort followed longitudinally for a mean of 3.5 (up to 10.2) years.
Washington Heights Inwood Columbia Aging Project, New York City
156 incident AD patients (mean age 83 years at diagnosis)
Vascular factors including medical history (heart disease, stroke, diabetes, hypertension), smoking, and pre-diagnosis blood lipid measurements (total cholesterol, High density lipoproteins (HDL-C), Low density lipoproteins (LDL-C) and triglycerides).
Main Outcome Measure
Change in a composite score of cognitive ability from diagnosis on.
In Generalized Estimating Equation (GEE) models (adjusted for age, race/ethnicity and education), higher cholesterol (total and LDL-C), and diabetes history were associated with faster cognitive decline. Each 10-unit increase in cholesterol and LDL-C was associated with a 10% of a standard deviation decrease in cognitive score per year of follow-up (p<0.001 for total cholesterol, p=0.001 for LDL-C). HDL and triglycerides were not associated with rate of decline. Diabetes history was associated with an additional 50% of a standard deviation decrease in cognitive score per year (p=0.05). History of heart disease and stroke were associated with cognitive decline among APOE-ε4 carriers only. In a final GEE model that included HDL-C, LDL-C and diabetes, only higher LDL-C was independently associated with faster cognitive decline.
Higher pre-diagnosis total cholesterol, LDL-C, and diabetes were associated with faster cognitive decline among incident AD patients, providing further evidence for the role of vascular risk factors in Alzheimer’s disease course.
Alzheimer’s Disease; Natural History; Epidemiology; Cholesterol; Vascular factors
To determine the association of blood pressure (BP) level and longterm fluctuation in BP with cerebrovascular disease.
Participants received structural MRI and BP measurements in 3, 24 month intervals prior to scanning. We derived the mean and standard deviation (SD) of the mean BP for each participant over the 3 intervals and divided them into four groups defined as above and below the group median (≤ 96.48 mmHg or >96.48mmHg) and further subdivided by the median standard deviation (below SD ≤ 7.21 mmHg or above SD > 7.21 mmHg). This scheme yielded four groups representing the full range of BP and fluctuations in BP. We examined differences in white matter hyperintensity (WMH) volume and brain infarctions across these groups.
The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from northern Manhattan.
686 non-demented older adults who received structural MRI and had BP measurements over three study visits.
WMH volume increased across the four groups in a linear fashion with the lowest WMH volume in the lowest mean/lowest SD group and the highest in the highest mean/highest SD group (F(3,610)=27.43, p=0.0017). Frequency of infarction also increased monotonically across groups (from 22% to 41%; p-for-trend=0.004).
Compared to individuals with low BP with low fluctuations in BP, the risk of cerebrovascular disease increases with increasing BP and BP fluctuation. Given that cerebrovascular disease is associated with disability, findings suggest that interventions should focus on longterm fluctuating BP as well as elevated BP.
blood pressure; cerebrovascular disease; white matter hyperintensities
To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles.
A longitudinal, community-based study.
New York, New York.
One thousand fifty-one Medicare recipients aged 65 years or older and residing in New York who were free of dementia or cognitive impairment at baseline.
Main Outcome Measures
We separately explored the associations of several vascular risk factors with late-onset Alzheimer disease (LOAD) using Cox proportional hazards models to identify factors that would contribute to the risk score. Then we estimated the score values of each factor based on their βcoefficients and created the LOAD vascular risk score by summing these individual scores.
Risk factors contributing to the risk score were age, sex, education, ethnicity, APOE ε4 genotype, history of diabetes, hypertension or smoking, high-density lipoprotein levels, and waist to hip ratio. The resulting risk score predicted dementia well. According to the vascular risk score quintiles, the risk to develop probable LOAD was 1.0 for persons with a score of 0 to 14 and increased 3.7-fold for persons with a score of 15 to 18, 3.6-fold for persons with a score of 19 to 22, 12.6-fold for persons with a score of 23 to 28, and 20.5-fold for persons with a score higher than 28.
While additional studies in other populations are needed to validate and further develop the score, our study suggests that this vascular risk score could be a valuable tool to identify elderly individuals who might be at risk of LOAD. This risk score could be used to identify persons at risk of LOAD, but can also be used to adjust for confounders in epidemiologic studies.
To reexamine the association of lipid levels with Alzheimer disease (AD) using Cox proportional hazards models.
Prospective cohort study.
Northern Manhattan, New York.
One thousand one hundred thirty elderly individuals free of cognitive impairment at baseline.
Main Outcome Measure
High-density lipoprotein cholesterol (HDL-C) levels.
Higher levels of HDL-C (>55 mg/dL) were associated with a decreased risk of both probable and possible AD and probable AD compared with lower HDL-C levels (hazard ratio, 0.4; 95% confidence interval, 0.2–0.9; P=.03 and hazard ratio, 0.4; 95% confidence interval, 0.2–0.9; P=.03). In addition, higher levels of total and non–HDL-C were associated with a decreased risk of AD in analyses adjusting for age, sex, education, ethnic group, and APOEe4 genotype.
High HDL-C levels in elderly individuals may be associated with a decreased risk of AD.
It has been suggested that low levels of estradiol and testosterone increase risk for dementia. However, results of the existing observational studies examining associations of endogenous sex hormones with cognition and dementia are conflicting. A possible explanation for these inconsistent findings could be the involvement of sex hormone-binding globulin (SHBG) in regulating sex hormone levels. In the present study, we examined whether SHBG levels were associated with development of AD and overall dementia in a cohort of elderly men and women free of dementia at baseline. We observed that in both men and women higher levels of SHBG were associated with an increased risk for AD and overall dementia. These results were independent of vascular risk factors and bioactive hormone levels. Whether SHBG is causally related to dementia or whether it is a surrogate marker for rate of biological aging and increased risk or for preclinical stage of dementia has to be elucidated.
SHBG; estradiol; testosterone; Alzheimer’s disease; dementia
Background and Objective
The validity of a self-reported stroke remains inconclusive. The objective of the present study was to validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard.
Design and Setting
Community-based cohort study of non-demented, ethnically diverse elderly in northern Manhattan.
High-resolution quantitative MRI was acquired on 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the χ2-test. Putative relations between factors potentially influencing the reporting of stroke, including memory performance, cognitive function and vascular risk factors were assessed using logistic regression models. Subsequently all analyses were repeated stratified by age, sex, ethnic group and level of education.
In analyses for the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4% and specificity was 78.9%. In analyses stratified by median of age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity: 36.7% (specificity 81.3%) vs. sensitivity 27.6% (specificity: 26.2%), p=0.02). Impaired memory, cognitive or language ability, and the presence of hypertension or myocardial infarction were associated with higher false-negatives.
Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.
Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (≥5%) in certain Asian and Latin American countries, but consistently low (1–3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for ∼30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE ε4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.
Purpose of the review
Alzheimer’s disease (AD) is the most common form of dementia. There are no known preventive or curative measures. There is increasing evidence for the role of total adiposity, usually measured clinically as body mass index (BMI), and central adiposity, measured in AD. This topic is of enormous public health importance given the global epidemic of high adiposity and its consequences.
Salient publications in 2007 and 2008 showed that a) central adiposity in middle age predicts dementia in old age; b) the relation between high adiposity and dementia is attenuated with older age; c) waist circumference in old age, a measure of central adiposity, may be a better predictor of dementia than BMI, d) lower BMI predicts dementia in the elderly; e) weight loss may precede dementia diagnosis by decades, which may explain seemingly paradoxical findings.
The possibility that high adiposity increases AD risk is alarming given global trends of overweight and obesity in the general population. However, prevention and manipulation of adiposity may also provide a means to prevent AD. Treatment of weight loss in AD may also be important but is beyond the score of this review.
Alzheimer’s disease; dementia; adiposity; overweight; obese; body weight
The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia.
There are conflicting data relating plasma lipids to the risk of Alzheimer's disease (AD). We explored the association of plasma lipids to mild cognitive impairment (MCI), a transitional stage between normal cognition and dementia, in a prospective community-based cohort study among randomly sampled Medicare recipients ≥65 years. Baseline data were collected from 1992 to 1994, follow-up data were collected at 18-month intervals.
Multivariate proportional hazards regression was used to relate plasma lipid levels to incident total MCI, amnestic MCI and nonamnestic MCI in 854 persons without MCI or dementia at baseline.
There were 324 cases of incident MCI, 153 cases of amnestic MCI and 171 cases of nonamnestic MCI during 4,189 person-years of follow-up. Higher levels of total cholesterol and LDL were associated with a decreased risk of total MCI in models adjusting for age and sex. However, these associations were attenuated after adjusting for ethnicity, education, APOEε4 and vascular risk factors. There was no association between lipids and the risk of amnestic or nonamnestic MCI, and there was no effect of lipid-lowering treatment on MCI risk.
Plasma lipid levels or lipid-lowering treatment in the elderly are not associated with the risk of MCI.
Plasma lipid levels; Mild cognitive impairment
To examine the impact of age, sex, ethnicity, and vascular disease on measures of brain morphology, including relative brain volume, ventricle volume, hippocampus and entorhinal cortex volume, and white matter hyperintensity (WMH) burden in a large community-based cohort of non-demented, ethnically diverse older adults.
Beginning in 2003, high-resolution quantitative magnetic resonance imaging (MRI) was acquired on 769 participants without dementia. The relations of age, sex, self reported vascular disease history, and ethnicity, with brain morphology was examined in a cross-sectional study using multiple linear regression analyses. Sex and ethnicity interactions were also considered.
The Washington Heights/Hamilton Heights Aging Project (WHICAP), a community-based epidemiological study of older adults from three ethnic groups (i.e., Caucasian, Hispanic, African American) from northern Manhattan.
Main outcome measures
Relative brain volume (absolute brain volume/cranial volume), ventricular volume, hippocampus and entorhinal cortex volumes were derived manually on high-resolution MRI scans. White matter hyperintensities were quantified semi-automatically on FLAIR-weighted MRI.
Increased age was associated with decreased relative brain volume and increased ventricular and WMH volume. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than Caucasians, but their associations with age were similar across ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and higher WMH burden, particularly among African Americans.
Increased age and vascular disease particularly among African Americans are associated with increased brain atrophy and WMH burden. African American and Hispanic participants have larger relative brain volumes and more WMH than Caucasians. Ethnic group differences in WMH severity appear to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.
This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance is also related to a higher risk of AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may present a unique opportunity for prevention and treatment of AD. Several studies in the prevention and treatment of T2D are currently conducting or have planned cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way.
adiposity; overweight; obesity; hyperinsulinemia; insulin; glucose; type 2 diabetes; alzheimer's disease; cognitive impairment
Background and Objective
There are conflicting data relating homocysteine levels to the risk of Alzheimer´s disease (AD). We sought to explore whether fasting plasma homocysteine is associated with the risk of mild cognitive impairment (MCI), an intermediate stage to dementia.
Fasting levels of plasma homocysteine were obtained from 678 elderly subjects chosen at random from a cohort of Medicare recipients. There was longitudinal data in 516 subjects without MCI or dementia at baseline who were followed for 2,705 person-years. The relation of plasma homocysteine with prevalent and incident all-cause MCI, amnestic MCI and non-amnestic MCI was assessed using logistic and Cox proportional hazards regression analyses.
There were 162 cases of prevalent MCI and 132 cases of incident MCI in 5,2 years of follow-up. There was no association between plasma homocysteine and prevalence of MCI or amnestic or non-amnestic MCI in the cross-sectional analyses. There was no association between higher homocysteine levels and a lower risk of all-cause MCI. Consistent with the cross-sectional analyses, there was no specific association with the amnestic or non-amnestic subtype of MCI in crude or adjusted models.
Plasma homocysteine levels measured at baseline were not related to MCI or its subtypes in an elderly multiethnic cohort.
homocysteine; dementia; mild cognitive impairment
vascular risk factors; cerebrovascular disease; cognitive impairment; dementia
The objective of this manuscript is to provide a comprehensive review of the epidemiologic evidence linking the continuum of adiposity, hyperinsulinemia, and diabetes with Alzheimer’s disease. The mechanisms for these associations remain to be elucidated, but may include direct actions from insulin, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of Alzheimer’s disease. The evidence relating adiposity in old age to Alzheimer’s disease is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of Alzheimer’s disease. Hyperinsulinemia is a risk factor for diabetes, and numerous studies have shown a relation of diabetes with higher Alzheimer’s disease risk. Most studies fail the take into account the continuum linking these risk factors which may result in underestimation of their importance in Alzheimer’s disease. The implication of these associations is that a large proportion of the world population may be at increased risk of Alzheimer’s disease given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and diabetes. However, if proven causal, these associations also present a unique opportunity for prevention and treatment of Alzheimer’s disease.
adiposity; overweight; obesity; hyperinsulinemia; insulin; glucose; diabetes; alzheimer’s disease; cognitive impairment
Background and Objective
There are conflicting data relating hypertension to the risk of Alzheime's disease (AD). We sought to explore whether hypertension is associated with the risk of mild cognitive impairment (MCI), an intermediate stage to dementia.
Design and Setting
Prospective community-based cohort study conducted in northern Manhattan.
Multivariate proportional hazards regression analyses, relating hypertension to incident all-cause MCI, amnestic MCI, and non-amnestic MCI in 918 persons without prevalent MCI at baseline followed for a mean of 4.7 years.
There were 334 cases of incident MCI, 160 cases of amnestic MCI and 174 cases of non-amnestic MCI during 4337 person years of follow-up. Hypertension was associated with an increased risk of all-cause MCI (HR 1.4, 95% CI 1.06-1.77, p=0.02) and non-amnestic MCI (HR 1.7, 95% CI 1.13-2.42, p=0.009) after adjusting for age and gender. Both associations were slightly attenuated in models additionally adjusting for stroke and other vascular risk factors. There was no association between hypertension and the risk of amnestic MCI (HR 1.1, 95% CI 0.79-1.63, p=0.49). Consistent with this association, hypertension was related with the slope of change in an executive ability score, but not with memory or language scores. There was no effect modification of the association between hypertension and MCI by APOEε4 genotype or use of antihypertensive medication.
A history of hypertension is related to a higher risk of MCI. The association seems to be stronger with the non-amnestic than the amnestic component of MCI. These findings suggest that prevention and treatment of hypertension may have an important impact in lowering the risk of cognitive impairment.
blood pressure; hypertension; mild cognitive impairment
We compared the frequency of structural and functional heart abnormalities, assessed using transthoracic echocardiography, among persons with Alzheimer's disease (AD), vascular dementia (VaD), stroke and healthy control subjects. Compared with controls, patients with AD were more likely to have aortic valve thickening, aortic valve regurgitation, left ventricular wall motion abnormalities, left ventricular hypertrophy and a reduced ejection fraction. Persons with VaD were more likely to have aortic valve regurgitation, but mitral valve thickening and triscuspid valve regurgitation were also more frequent. In the absence of dementia, persons with stroke differed from controls by more frequent mitral valve calcifications. With the increasing prevalence of AD and VaD, clinicians have to be more attentive to the presence of structural heart disease and its complications in persons with these conditions.
Heart disease; echocardiography; dementia; Alzheimer's disease; vascular dementia