Showing papers by "José A. Luchsinger published in 2012"

Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community.

Abstract: Background New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. Objective To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. Design A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. Setting The Washington Heights/Inwood Columbia Aging Project. Participants Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. Main Outcome Measure Incident AD. Results White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). Conclusions The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.

Type 2 diabetes and cognitive impairment: linking mechanisms.

Abstract: 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 the mechanisms are.

Central obesity in the elderly is related to late-onset Alzheimer disease.

Abstract: The evidence relating obesity measured with body mass index (BMI) in the elderly to late-onset Alzheimer disease (LOAD) is conflicting. Central obesity in middle age is related to a higher risk of LOAD, but data in the elderly are lacking. We explored whether measures of central obesity, waist circumference, and waist to hip ratio (WHR) were better predictors of LOAD compared with BMI in the elderly. Participants were 1459 persons aged 65 years and older without dementia at baseline, with follow-up, and with anthropometric data from a longitudinal study of aging in New York City. Proportional hazards regression was used for multivariable analyses relating BMI, waist circumference, and WHR to LOAD. There were 145 cases of Alzheimer disease in 5734 person-years of follow-up. Only WHR was related to higher LOAD risk (hazard ratio of the fourth quartile compared with the first=2.5; 95% confidence interval=1.3, 4.7) after adjustment for age, sex, education, ethnic group, Apolipoprotein E-e4, type 2 diabetes, hypertension, non-high-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, and stroke. Our results support the notion that central obesity is related to a higher risk of LOAD.

Genetic Variants in the Fat and Obesity Associated (FTO) Gene and Risk of Alzheimer's Disease

Abstract: Background Recent studies showed that polymorphisms in the Fat and Obesity-Associated (FTO) gene have robust effects on obesity, obesity-related traits and endophenotypes associated with Alzheimer's disease (AD). Methods We used 1,877 Caucasian cases and controls from the NIA-LOAD study and 1,093 Caribbean Hispanics to further explore the association of FTO with AD. Using logistic regression, we assessed 42 SNPs in introns 1 and 2, the region previously reported to be associated with AD endophenotypes, which had been derived by genome-wide screenings. In addition, we performed gene expression analyses of neuropathologically confirmed AD cases and controls of two independent datasets (19 AD cases, 10 controls; 176 AD cases, 188 controls) using within- and between-group factors ANOVA of log10 transformed rank invariant normalized expression data. Results In the NIALOAD study, one SNP was significantly associated with AD and three additional markers were close to significance (rs6499640, rs10852521, rs16945088, rs8044769, FDR p-value: 0.05 0.9) with the previously reported SNPs. In the Caribbean Hispanic dataset, we identified three SNPs (rs17219084, rs11075996, rs11075997, FDR p-value: 0.009

Memory after silent stroke: Hippocampus and infarcts both matter

Abstract: Objective: Memory decline commonly occurs among elderly individuals. This observation is often attributed to early neurodegenerative changes in the hippocampus and related brain regions. However, the contribution of vascular lesions, such as brain infarcts, to hippocampal integrity and age-associated memory decline remains unclear. Methods: We studied 658 elderly participants without dementia from a prospective, community-based study on aging and dementia who received high-resolution structural MRI. Cortical and subcortical infarcts were identified, and hippocampal and relative brain volumes were calculated following standard protocols. Summary scores reflecting performance on tasks of memory, language, processing speed, and visuospatial function were derived from a comprehensive neuropsychological battery. We used multiple regression analyses to relate cortical and subcortical infarcts, hippocampal and relative brain volume, to measures of cognitive performance in domains of memory, language, processing speed, and visuospatial ability. Results: Presence of brain infarcts was associated with a smaller hippocampus. Smaller hippocampus volume was associated with poorer memory specifically. Brain infarcts were associated with poorer memory and cognitive performance in all other domains, which was independent of hippocampus volume. Conclusions: Both hippocampal volume and brain infarcts independently contribute to memory performance in elderly individuals without dementia. Given that age-associated neurodegenerative conditions, such as Alzheimer disease, are defined primarily by impairment in memory, these findings have clinical implications for prevention and for identification of pathogenic factors associated with disease symptomatology.

Nutrient intake and plasma β-amyloid

Abstract: Objective: The widely reported associations between various nutrients and cognition may occur through many biologic pathways including those of β-amyloid (Aβ). However, little is known about the possible associations of dietary factors with plasma Aβ40 or Aβ42. The aim of the current study was to evaluate the association between nutrient intake and plasma Aβ levels. Methods: In this cross-sectional study, plasma Aβ40 and Aβ42 and dietary data were obtained from 1,219 cognitively healthy elderly (age >65 years), who were participants in a community-based multiethnic cohort. Information on dietary intake was obtained 1.2 years, on average, before Aβ assay. The associations of plasma Aβ40 and Aβ42 levels and dietary intake of 10 nutrients were examined using linear regression models, adjusted for age, gender, ethnicity, education, caloric intake, apolipoprotein E genotype, and recruitment wave. Nutrients examined included saturated fatty acid, monounsaturated fatty acid, ω-3 polyunsaturated fatty acid (PUFA), ω-6 PUFA, vitamin E, vitamin C, β-carotene, vitamin B 12 , folate, and vitamin D. Results: In unadjusted models that simultaneously included all nutrients, higher intake of ω-3 PUFA was associated with lower levels of Aβ40 (β = −24.7, p p p = 0.02), whereas its association with Aβ40 was attenuated (β = −11.96, p = 0.06). Other nutrients were not associated with plasma Aβ levels. Conclusions: Our data suggest that higher dietary intake of ω-3 PUFA is associated with lower plasma levels of Aβ42, a profile linked with reduced risk of incident AD and slower cognitive decline in our cohort.

Depressive symptoms, antidepressant use, and brain volumes on MRI in a population-based cohort of old persons without dementia

Abstract: We examined 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 (WMH) 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 WMH at 1.5 Tesla MRI and data on current depression, defined as a score of 4 or higher on the 10-item Center for Epidemiologic Studies-Depression (CES-D) scale, or use of antidepressants. Multiple linear regression analyses adjusted for age, gender, 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.

Type 2 Diabetes and Ethnic Disparities in Cognitive Impairment

Abstract: OBJECTIVES: We explored whether ethnic differences in type 2 diabetes (T2D) explain ethnic disparities in cognitive impairment. DESIGN: Longitudinal study. SETTING: A cohort study of multiethnic community-dwelling elderly persons in Northern Manhattan, New York. PARTICIPANTS: 941 participants aged > or =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 > or = .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. RESULTS: 448 participants developed CID; 69 (31.4%) non-Hispanic whites (whites); 152 (48.6%) non-Hispanic-blacks (blacks); 227 (55.6%) Hispanics, P < .001. T2D prevalence was 8.2% in Whites, 20.1% in blacks, and 19.6% in Hispanics, P < .001. Controlling for age, sex, education, and APOE E4, 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 = .06). We estimated that reducing the ethnic disparities in diabetes prevalence could reduce the CID ethnic disparities by 17%. CONCLUSIONS: Reducing ethnic differences in T2D prevalence could partially reduce ethnic differences in incident CID. Ethn Dis . 2012 Winter;22(1):38-44.

Adiponectin and all-cause mortality in elderly people with type 2 diabetes.

Abstract: OBJECTIVE To assess the association between serum adiponectin level and all-cause mortality in people with type 2 diabetes. Because of the insulin-sensitizing, anti-inflammatory and antiatherogenic effects of adiponectin, we hypothesized that higher adiponectin level would be associated with lower all-cause mortality. RESEARCH DESIGN AND METHODS A total of 609 men and women aged 72 ± 6.3 years with type 2 diabetes and information on total and high molecular weight adiponectin were followed for a median of 5 years. The longitudinal association between adiponectin and all-cause mortality was analyzed with Cox proportional hazards models with time from adiponectin measurement to death as the time-to-event variable. Analyses were adjusted for demographic variables and significant diabetes parameters, significant cardiovascular parameters, and significant diabetes medications. RESULTS Total and high molecular weight adiponectin were highly correlated. The highest adiponectin quartile was strongly associated with higher all-cause mortality compared with the lowest quartile (hazard ratio = 4.0 [95% CI: 1.7–9.2]) in the fully adjusted model. These results did not change in analyses stratified by sex and thiazolidinedione use, after exclusion of people who died within one year of adiponectin measurement, or when change in weight before adiponectin measurement was considered. CONCLUSION Contrary to our hypothesis, higher adiponectin level was related to higher all-cause mortality. This association was not explained by confounding by other characteristics, including medications or preceding weight loss.

The Northern Manhattan Caregiver Intervention Project: a randomised trial testing the effectiveness of a dementia caregiver intervention in Hispanics in New York City

Abstract: Objectives 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. Trial Registration www.ClinicalTrials.gov NCT01306695.

Lessons from Epidemiologic Research about Risk Factors, Modifiers, and Progression of Late Onset Alzheimer’s Disease in New York City at Columbia University Medical Center

Abstract: This review summarizes the findings and importance of 12 articles from research at Columbia University in New York City that were among the most cited in the literature between 2006 and 2011. The 12 articles summarized in this review made important contributions to the field of Alzheimer's disease in the last 5 years. Four of the articles established the Mediterranean diet as a food consumption pattern that may prevent Alzheimer's disease in addition to physical activity. Two of the articles advanced our knowledge of predictors of conversion from mild cognitive impairment to dementia. Four of the articles provided important knowledge of risk factors for the progression of Alzheimer's disease and its complications. Lastly, one of the articles laid the theoretical framework for the study of cognitive reserve, an important modifier of the manifestation of Alzheimer's disease. These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease

Lessons from Epidemiologic Research about Risk Factors, Modifiers, and Progression of Late Onset Alzheimer's Disease in New York City at Columbia

Abstract: 16 Abstract. This review summarizes the findings and importance of 12 articles from research at Columbia University in New York City that were among the most cited in the literature between 2006 and 2011. The 12 articles summarized in this review made important contributions to the field of Alzheimer's disease in the last 5 years. Four of the articles established the Mediterranean diet as a food consumption pattern that may prevent Alzheimer's disease in addition to physical activity. Two of the articles advanced our knowledge of predictors of conversion from mild cognitive impairment to dementia. Four of the articles provided important knowledge of risk factors for the progression of Alzheimer's disease and its complications. Lastly, one of the articles laid the theoretical framework for the study of cognitive reserve, an important modifier of the manifestation of Alzheimer's disease. These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease. 17 18 19 20 21 22 23 24 25

Protocol for the Northern Manhattan Diabetes Community Outreach Project. A randomised trial of a community health worker intervention to improve diabetes care in Hispanic adults

Abstract: Objective Hispanics in the USA are affected by the diabetes epidemic disproportionately, and they consistently have lower access to care, poorer control of the disease and higher risk of complications. This study evaluates whether a community health worker (CHW) intervention may improve clinically relevant markers of diabetes care in adult underserved Hispanics. Methods and analysis The Northern Manhattan Diabetes Community Outreach Project (NOCHOP) is a two-armed randomised controlled trial to be performed as a community-based participatory research study performed in a Primary Care Setting in Northern Manhattan (New York City). 360 Hispanic adults with poorly controlled type 2 diabetes mellitus (haemoglobin A1c >8%), aged 35–70 years, will be randomised at a 1:1 ratio, within Primary Care Provider clusters. The two study arms are (1) a 12-month CHW intervention and (2) enhanced usual care (educational materials mailed at 4-month intervals, preceded by phone calls). The end points, assessed after 12 months, are primary = haemoglobin A1c and secondary = blood pressure and low-density lipoprotein-cholesterol levels. In addition, the study will describe the CHW intervention in terms of components and intensity and will assess its effects on (1) medication adherence, (2) medication intensification, (3) diet and (4) physical activity. Ethics and dissemination All participants will provide informed consent; the study protocol has been approved by the Institutional Review Board of Columbia University Medical Center. CHW interventions hold great promise in improving the well-being of minority populations who suffer from diabetes mellitus. The NOCHOP study will provide valuable information about the efficacy of those interventions vis-a-vis clinically relevant end points and will inform policy makers through a detailed characterisation of the programme and its effects. Clinical trial registration number NCT00787475 at clinicaltrials.gov.

White matter hyperintensities may mediate the relationship between inflammation and cognition in an elderly cohort

Abstract: Background:Mild cognitive impairment (MCI) represents a window of opportunity to delay or prevent the onset of dementia. Exercise is one promising intervention strategy. However, the efficacy of resistance versus aerobic training to improve cognitive functions in seniors with MCI has not previously been examined. Methods: In this 6-month randomized controlled trial, 86 women aged 70-80 years with probable MCI were assigned to one of three groups: twice-weekly resistance training, twice-weekly aerobic training, or twice-weekly balance and tone exercises (control group). The primary outcome measure was the specific executive cognitive function of conflict resolution and selective attention, as measured by Stroop Test performance. Secondary outcomes included set-shifting, working memory, associative memory, regional patterns of functional brain plasticity, everyday problem solving ability, general balance and mobility, and general cardiovascular capacity. Results: Compared with the balance and tone group, the resistance training group significantly improved their performance on the Stroop Test. In addition, the resistance training group improved performance on the associative memory task, which corresponded to increased functional plasticity in three regions of cortex essential for associative memory performance the right lingual and occipital fusiform gyri and the right frontal pole. In contrast, the aerobic training group showed significantly improved general balance andmobility, and cardiovascular capacity post-intervention. Conclusions: Our results suggest that twice-weekly resistance training may be a promising strategy to alter the trajectory of cognitive decline in seniors with MCI.