Vascular risk factors for Alzheimer disease (AD) and vascular dementia (VaD) have been evaluated; however, few studies have compared risks by dementia subtypes and sex. We evaluated relationships between cardiovascular risk factors (hypertension, high cholesterol, diabetes mellitus, and obesity), events (stroke, coronary artery bypass graft surgery, and myocardial infarction), and subsequent risk of AD and VaD by sex in a community-based cohort of 3264 Cache County residents aged 65 or older. Cardiovascular history was ascertained by self-report or proxy-report in detailed interviews. AD and VaD were diagnosed using standard criteria. Estimates from discrete-time survival models showed no association between self-reported history of hypertension and high cholesterol and AD after adjustments. Hypertension increased the risk of VaD [adjusted hazard ratio (aHR) 2.42, 95% confidence interval (CI) 0.95-7.44]. Obesity increased the risk of AD in females (aHR 2.23, 95% CI 1.09-4.30) but not males. Diabetes increased the risk of VaD in females after adjustments (aHR 3.33, 95% CI 1.03-9.78) but not males. The risk of VaD after stroke was increased in females (aHR 16.90, 95% CI 5.58-49.03) and males (aHR 10.95, 95% CI 2.48-44.78). The results indicate that vascular factors increase risks for AD and VaD differentially by sex. Future studies should focus on specific causal pathways for each of these factors with regard to sex to determine if sex differences in the prevalence of vascular factors have an influence on sex differences in dementia risk.
Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia and CIND.Participants in the Aging, Demographic, and Memory Study (ADAMS) were evaluated for cognitive impairment using a comprehensive in-home assessment. A total of 456 individuals aged 72 years and older, who were not demented at baseline, were followed longitudinally from August 2001 to December 2009. An expert consensus panel assigned a diagnosis of normal cognition, CIND, or dementia and its subtypes. Using a population-weighted sample, we estimated the incidence of dementia, Alzheimer disease (AD), vascular dementia (VaD), and CIND by age. We also estimated the incidence of progression from CIND to dementia.The incidence of dementia was 33.3 (standard error [SE], 4.2) per 1,000 person-years and 22.9 (SE, 2.9) per 1,000 person-years for AD. The incidence of CIND was 60.4 (SE, 7.2) cases per 1,000 person-years. An estimated 120.3 (SE, 16.9) individuals per 1,000 person-years progressed from CIND to dementia. Over a 5.9-year period, about 3.4 million individuals aged 72 and older in the United States developed incident dementia, of whom approximately 2.3 million developed AD, and about 637,000 developed VaD. Over this same period, almost 4.8 million individuals developed incident CIND.The incidence of CIND is greater than the incidence of dementia, and those with CIND are at high risk of progressing to dementia, making CIND a potentially valuable target for treatments aimed at slowing cognitive decline.
Introduction I. Geriatric Neuropsychological Assessment A. Assessment of Common Geriatric Conditions 1. An Integrated Model for Geriatric Neuropsychological Assessment, Guy G. Potter and Deborah K. Attix 2. Normal Aging and Mild Cognitive Impairment, Glenn Smith and Beth K. Rush 3. Neurodegenerative Dementias, Kathleen A. Welsh-Bohmer and Lauren H. Warren 4. Stable and Slowly Progressive Dementias, M. Allison Cato and Bruce A. Crosson 5. Potentially Reversible Cognitive Symptoms in Older Adults, Wes S. Houston and Mark W. Bondi B. Specific Considerations 6. Using Norms in Neuropsychological Assessment of the Elderly, Robyn M. Busch, Gordon J. Chelune, and Yana Suchy 7. Functional Assessment, Daniel Marson and Katina R. Hebert 8. Cultural Issues, Jennifer J. Manly 9. Feedback, Joanne Green II. Geriatric Neuropsychological Intervention A. Cognitive Training and Compensatory Techniques 10. An Integrated Model for Geriatric Neuropsychological Intervention, Deborah K. Attix 11. Training of Cognitive and Functionally Relevant Skills in Mild Alzheimer's Disease: An Integrated Approach, David Loewenstein and Amarilis Acevedo 12. Spaced Retrieval: A Model for Dissemination of a Cognitive Intervention for Persons with Dementia, Cameron J. Camp 13. Multitechnique Program Approaches, Linda Clare 14. Language Interventions in Dementia, Cynthia K. Thompson and Nancy Johnson 15. External Aids, Michelle S. Bourgeois B. Psychotherapeutic Interventions 16. Behavioral Treatment of Affective Disorders and Associated Symptoms, Rebecca G. Logsdon, Susan M. McCurry, and Linda Teri 17. Behavioral Treatment of Impaired Functioning and Behavioral Symptoms, Ann Louise Barrick 18. Group Psychotherapy Approaches for Dementia, Guy G. Potter, Deborah K. Attix, and Cory K. Chen 19. Pharmacological and Other Treatment Strategies for Alzheimer's Disease, Kathleen Hayden and Mary Sano
The Montreal Cognitive Assessment (MoCA) is a widely used cognitive screening tool for Mild Cognitive Impairment (MCI) and early Alzheimer's disease (AD). However, there are no published population-based studies to guide its use with Russian populations. The aim of the current study was to investigate the impact of demographic variables on MoCA total score, and to describe its use as a screening tool for AD prevention studies in an urban population of older adults from Tomsk, Russia. Volunteers (N=1377) aged 60–89 years were identified using a centralized medical care system database. Subjects were asked by phone to participate in a pre-screening study for a future primary prevention clinical trial. Participants were administered the Russian translation of the MoCA, and specifically asked if they would consider participating in a pharmacological trial for the prevention of AD. No significant differences in MoCA total score were found between men (N=350) and women (N=1027). Lower education was associated with poorer performance on MoCA total scores. Those with less than high school education had the lowest total MoCA scores (17.8±0.3), followed by high school graduates (21.7±0.3), those with some college (21.5±0.2), college graduates (22.9±0.1), and those with a graduate degree (23.7±0.4), p<0.0001. Older age was associated with poorer performance on MoCA total scores. Individuals aged 83–89 years (n=38) had the lowest MoCA total scores (19.2±0.6), followed by ages 79–82, 19.7±0.4 (n=90), ages 73–78, 20.8±0.2 (n=383), and ages 67–72, 22.01±0.2 (n=501); ages 60–66 performed best, 23.3±0.2 (n=365), p<0.0001. Most participants (93%) expressed interest in participating in a pharmacological, primary prevention clinical trial. There were no differences in interest based on gender or total MoCA score. However, individuals in the oldest age band were less likely to express interest (95% of 60–66 year-olds and 82% of 83–89 year-olds, p<0.0001). The MoCA was a useful screening tool in a Russian elderly population, though education and age should be considered when using the MoCA to screen for clinical trials. The methods used in this study can be effective to recruit older Russian adults for pharmacological prevention trials.
Abstract Introduction There is conflicting evidence whether high‐density lipoprotein cholesterol (HDL‐C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein ( CETP ) locus is associated with altered HDL‐C. We aimed to assess AD risk by genetically predicted HDL‐C. Methods Ten single nucleotide polymorphisms within the CETP locus predicting HDL‐C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR‐Egger. Results Based on 10 single nucleotide polymorphisms distinctly predicting HDL‐C in the CETP locus, we found that HDL‐C was not associated with risk of AD ( P > .7). Discussion Our study does not support the role of HDL‐C on risk of AD through HDL‐C altered by CETP . This study does not rule out other mechanisms by which HDL‐C affects risk of AD.
Previous estimates of the prevalence of geriatric depression have varied. There are few large population-based studies; most of these focused on individuals younger than 80 years. No US studies have been published since the advent of the newer antidepressant agents.In 1995 through 1996, as part of a large population study, we examined the current and lifetime prevalence of depressive disorders in 4,559 nondemented individuals aged 65 to 100 years. This sample represented 90% of the elderly population of Cache County, Utah. Using a modified version of the Diagnostic Interview Schedule, we ascertained past and present DSM-IV major depression, dysthymia, and subclinical depressive disorders. Medication use was determined through a structured interview and a "medicine chest inventory."Point prevalence of major depression was estimated at 4.4% in women and 2.7% in men (P= .003). Other depressive syndromes were surprisingly uncommon (combined point prevalence, 1.6%). Among subjects with current major depression, 35.7% were taking an antidepressant (mostly selective serotonin reuptake inhibitors) and 27.4% a sedative/hypnotic. The current prevalence of major depression did not change appreciably with age. Estimated lifetime prevalence of major depression was 20.4% in women and 9.6% in men (P<.001), decreasing with age.These estimates for prevalence of major depression are higher than those reported previously in North American studies. Treatment with antidepressants was more common than reported previously, but was still lacking in most individuals with major depression. The prevalence of subsyndromal depressive symptoms was low, possibly because of unusual characteristics of the population.
SNPs located in the gene encoding the regulatory subunit of the protein phosphatase 2B (PPP3R1, rs1868402), and the microtubule-associated protein tau (MAPT, rs3785883) gene, were recently reported to show association with CSF tau levels. Cruchaga et al 2010 also reported that rs1868402 and rs3785883 were associated with an increased rate of progression of Alzheimer's disease (AD) as measured by the Clinical Dementia Rating sum of boxes scores (CDR-sb). We attempted to validate these associations in an independent, population-based sample of incident AD cases from the Cache County Memory Study and tested them for association with the rate of progression of AD. 68 AD cases met criteria for inclusion: a global CDR-sb of less than 1 (mild) at their initial clinical assessment and CDR-sb data for at least two time points. We genotyped rs1868402 and rs3785883 using custom Taqman Assays (Applied Biosystems), utilizing the ABI ViiA 7 Instrument and the ABI Genotyper software. Subjects had an average of 5 assessments and average time from first to final assessment was 3.17 years. We used linear mixed models to identify associations between these SNPs and the trajectory of CDR-sb. Analyses were performed using Proc Mixed in SAS. We found a significant association between rs3785883 and the rate of progression of AD (p = 0.015), but failed to detect an association for rs1868402 (p = 0.30). Our analyses support the evidence that rs3785883 is associated with the rate of progression of AD. Although our results with rs1868402 were not statistically significant, the direction and magnitude of the effect observed in our data is consistent with the previous findings. We are currently genotyping additional samples and performing a combined analysis of these samples and the data from the original report. The data reported here and the additional genotyping and analyses to be presented at the meeting will provide a better understanding of the genetic variability that influences the rate of progression of Alzheimer's disease and could provide novel insights into possible preventative and therapeutic strategies.
Abstract The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. ( JINS , 2012, 18 , 1–12)
