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.
Published familial relative risk (RR) estimates for Alzheimer's Disease (AD) typically focus on summary data from close relatives, rather than on complete family history for an individual. The risk estimates presented avoid common recall, recruitment, and ascertainment biases, and provide more individualized risk estimates based on a specific family history of AD. We use a population-based genealogy resource to estimate the risk for death from AD based on complete family history of death from AD. The Utah Population Data Base (UPDB), a computerized genealogical resource linked to state death certificates from 1904, was analyzed. Over 1 million individuals with at least 12 of their 14 immediate ancestors were analyzed. All individuals with specific family histories of AD were identified in the UPDB (probands) and the observed number of AD deaths among these probands was compared to the expected number of AD deaths using internal cohort-specific rates from Utah death certificates to obtain a RR estimate. We considered family history from first- to third-degree relatives, number of relatives affected, paternal versus maternal family history, and age at diagnosis. Significantly elevated RRs for AD mortality were observed based on the presence of any number of affected first-degree relatives; any number of affected second-degree relatives in the presence of at least 1 first-degree relative; and in the presence of at least 2 third-degree relatives, even in the absence of affected first- and second-degree relatives. There is evidence for increased risk via maternal versus paternal inheritance, and for higher risks for males than females given equivalent family history. This study provides unbiased, population-based estimates of AD risk based on an individual's family history for AD death. AD risk estimates derived from specific family history are as informative (or more so) and more economical than those estimated based on genotypes. Multiple family histories conferring 2-3 times increased risk for dying from AD are identified. Using detailed AD family history in the planning of screening, treatment, and monitoring opens additional avenues for implementation of more sound translational medicine practices, and decreasing morbidity and mortality in patients and their families.
Background: Late-life cognitive impairment places increasing levels of burden on caregivers.Electronic reminding aids have potential to improve functioning in those with memory impairment.In a pilot study, we examined adoption of a smartphone reminding application and its association with indicators of caregiver burden.Methods: 30 participant-caregiver dyads used the application for up to six months.Participants (33% female) were age M(SD) 88.65(3.08),with M(SD) education 14.37(3.15).Caregivers (73% female) consisted of spouses (47%) and adult children.Dyads were trained to use the application.Baseline and follow-up measures included demographics, participant cognition (Modified Mini-Mental State Exam), caregiving time (Caregiver Activity Survey; CAS), caregiver burden (Zarit Burden Inventory-Short form), and caregiver mood (Geriatric Depression Scale).Measures of application usage included duration of use, number of reminders set, and percent of reminders acknowledged (%Ack).Results: In a series of multiple regressions, duration of application use and number of reminders set were associated with higher baseline CAS (B=.65,p=.057;B=29.65,p=.074,respectively); %Ack was inversely related to duration of application use (B=-3.57,p<.001),baseline caregiver burden (B=-5.95;p=.077)and participant age and education (B=-1.43,p=.053;B=-2.21,p=.013).Regarding caregiver outcomes, depression was associated with higher percentage of applications set by caregiver (B=.115,p=.028);lower six-month CAS was associated with higher %Ack (B=-.134,p=.084).Conclusion: Results show utility of a smartphone application, evidenced by lower caregiving time at six-month follow-up with greater degree of application use.Application use was associated with baseline caregiving time and burden.Future analyses will examine duration of effect at one year and factors predictive of sustained use.
Alzheimer's disease (AD) is the most common cause of dementia and AD risk clusters within families. Part of the familial aggregation of AD is accounted for by excess maternal vs. paternal inheritance, a pattern consistent with mitochondrial inheritance. The role of specific mitochondrial DNA (mtDNA) variants and haplogroups in AD risk is uncertain.We determined the complete mitochondrial genome sequence of 1007 participants in the Cache County Study on Memory in Aging, a population-based prospective cohort study of dementia in northern Utah. AD diagnoses were made with a multi-stage protocol that included clinical examination and review by a panel of clinical experts. We used TreeScanning, a statistically robust approach based on haplotype networks, to analyze the mtDNA sequence data. Participants with major mitochondrial haplotypes H6A1A and H6A1B showed a reduced risk of AD (p=0.017, corrected for multiple comparisons). The protective haplotypes were defined by three variants: m.3915G>A, m.4727A>G, and m.9380G>A. These three variants characterize two different major haplogroups. Together m.4727A>G and m.9380G>A define H6A1, and it has been suggested m.3915G>A defines H6A. Additional variants differentiate H6A1A and H6A1B; however, none of these variants had a significant relationship with AD case-control status.Our findings provide evidence of a reduced risk of AD for individuals with mtDNA haplotypes H6A1A and H6A1B. These findings are the results of the largest study to date with complete mtDNA genome sequence data, yet the functional significance of the associated haplotypes remains unknown and replication in others studies is necessary.
Sleep medications such as benzodiazepines, tetra- or tri-cyclics, antihistamines, and certain antidepressants are commonly prescribed to older adults. Adverse events have been reported with use of some of these medications such as memory problems and increased risk of falls. Several classes of sleep medication are known to disrupt the sleep-wake cycle and result in decreases in slow-wave sleep and Rapid Eye Movement (REM) sleep, which are important for memory consolidation. We examined the association between use of sleep medications and risk of Alzheimer's Disease (AD) in a community sample of older adults in Cache County, Utah and if this association varied by sex. 3,656 participants without dementia at baseline (57.8% female) participated in a longitudinal study that assessed risk factors for AD and cognitive decline. Dementia screenings and assessments were conducted in four triennial waves spanning 12 years to determine dementia and non-case (screened or evaluated negative for cognitive impairment). Dementia was determined based on a clinical assessment and diagnosis of AD was made using DSM-III-R and NINCDS-ADRDA criteria. Medication history was obtained via interview and visual inspection of all medications. Use of any sleep medication (time-varying) and time to dementia or right censoring was modeled using Cox proportional hazards regression in separate models for males and females. Covariates tested were sleep disturbance, depression status, age, presence of APOE E4 allele, and educational attainment. In men, use of sleep medication was associated with 3.6 times increased risk of developing AD (HR=3.604, p = 0.0001) compared to those who did not use sleep medications. In women, risk of AD varied by endorsement of a sleep disturbance: women who did not endorse a sleep disturbance but used sleep medications were nearly 4 times at greater risk for developing AD (3.916; p = .0001) whereas those without sleep disturbance and who used sleep medications were at a 35.2% reduced risk of developing AD. Caution is warranted in prescribing sleep medications for older adults, though effects in AD risk vary by sex and endorsement of sleep disturbance. Further research is needed to determine the mechanisms underlying the observed sex differences.
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.
