Modelling mobile-based technology adoption among people with dementia.

The work described in this paper builds upon our previous research on adoption modelling and aims to identify the best subset of features that could offer a better understanding of technology adoption. The current work is based on the analysis and fusion of two datasets that provide detailed information on background, psychosocial, and medical history of the subjects. In the process of modelling adoption, feature selection is carried out followed by empirical analysis to identify the best classification models. With a more detailed set of features including psychosocial and medical history information, the developed adoption model, using kNN algorithm, achieved a prediction accuracy of 99.41% when tested on 173 participants. The second-best algorithm built, using NN, achieved 94.08% accuracy. Both these results have improved accuracy in comparison to the best accuracy achieved (92.48%) in our previous work, based on psychosocial and self-reported health data for the same cohort. It has been found that psychosocial data is better than medical data for predicting technology adoption. However, for the best results, we should use a combination of psychosocial and medical data where it is preferable that the latter is provided from reliable medical sources, rather than self-reported.

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-ß precursor protein (APP) and extracellular Aß42 and Aß40 (the 42- and 40-residue isoforms of the amyloid-ß peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aß42 and Aß40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Sleep quality as predictor of BMI in non-depressed caregivers of people with dementia.

PURPOSE: Although most cross-sectional and longitudinal studies of children and adolescents have found a link between short duration of sleep and obesity, the literature related to adults provides a non-consensual framework. The aim of the present study was to examine the association between sleep quality and BMI in a population of caregivers looking after people suffering from dementia, with a view to identifying the moderating role of depressive symptoms in the relationship between sleep problems and BMI. METHODS: A total of 117 subjects took part in the study, filling in a Sociodemographic Questionnaire, the Pittsburgh Sleep Quality Index, the Eating behavior Questionnaire and The Center for Epidemiologic Studies-Depression. RESULTS: Depressive symptoms were greater in females than in males. The sample was divided into two subgroups based on depressive-symptom scores. Only within the subsample with low depressive symptoms, higher sleep disturbances influenced BMI positively. Within this subsample of participants with low depressive symptoms, the variables that seem to play a pivotal role in explaining a high BMI are: female gender, sleep problems, and diet quality, while within the subsample with high depressive symptoms only the female gender factor was found to influence BMI. CONCLUSIONS: Depressive symptoms seem to act as moderators in the relationship between sleep and BMI. They should be evaluated to identify the risk of high BMI, and to differentiate clinical intervention, at least in this population, which experiences the stress of caregiving chronically, though not suffering from clinical eating disorders. LEVEL OF EVIDENCE: Level II, cross-sectional study.

Is poor sleep associated with obesity in older adults? A narrative review of the literature.

INTRODUCTION: To address the worldwide epidemic of obesity, a sizable literature implicates sleep problems in the onset of obesity in younger populations. However, less is known about how this process may operate among older adults, which is of concern, given demographic shifts that have resulted in a much higher proportion of developed nations around the world reaching late life. METHODS: We offer a current review of the literature studying older adults and examining associations between sleep quality and obesity in this population. We consider both subjective and objectively measured sleep as well as both cross-sectional and longitudinal studies offering stronger causal inference. RESULTS: We discuss seemingly contradictory literature showing that shorter sleep duration as well as longer sleep duration are associated with obesity risk, then review studies that tested for non-linear relationships and reported a U-shape pattern, suggesting that too much or too little sleep is detrimental. Besides sleep duration, we discuss evidence showing that other forms of sleep dysfunction related to night-time awakenings, REM sleep, slow-wave sleep, and daytime sleepiness, which are indicators of sleep quality, are also linked to obesity. Specific psychological and physiological mediators and moderators, suggesting possible mechanisms whereby sleep problems may affect obesity in older adults, are described. CONCLUSION: We conclude by discussing areas, where additional research could help clarify this association, considering such factors as medical comorbidities common in late life, and health-related behaviors that may stem from poor sleep (such as disordered eating behavior). Such insights will have great value for clinical practice. LEVEL OF EVIDENCE: Level V, narrative review.

Presenilin E318G variant and Alzheimer's disease risk: the Cache County study.

BACKGROUND: Alzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer's disease, including Presenilin 1 (PSEN1). Multiple studies have attempted to locate novel variants in the PSEN1 gene that affect Alzheimer's disease status. A recent study suggested that one of these variants, PSEN1 E318G (rs17125721), significantly affects Alzheimer's disease status in a large case-control dataset, particularly in connection with the APOEε4 allele. METHODS: Our study looks at the same variant in the Cache County Study on Memory and Aging, a large population-based dataset. We tested for association between E318G genotype and Alzheimer's disease status by running a series of Fisher's exact tests. We also performed logistic regression to test for an additive effect of E318G genotype on Alzheimer's disease status and for the existence of an interaction between E318G and APOEε4. RESULTS: In our Fisher's exact test, it appeared that APOEε4 carriers with an E318G allele have slightly higher risk for AD than those without the allele (3.3 vs. 3.8); however, the 95 % confidence intervals of those estimates overlapped completely, indicating non-significance. Our logistic regression model found a positive but non-significant main effect for E318G (p = 0.895). The interaction term between E318G and APOEε4 was also non-significant (p = 0.689). CONCLUSIONS: Our findings do not provide significant support for E318G as a risk factor for AD in APOEε4 carriers. Our calculations indicated that the overall sample used in the logistic regression models was adequately powered to detect the sort of effect sizes observed previously. However, the power analyses of our Fisher's exact tests indicate that our partitioned data was underpowered, particularly in regards to the low number of E318G carriers, both AD cases and controls, in the Cache county dataset. Thus, the differences in types of datasets used may help to explain the difference in effect magnitudes seen. Analyses in additional case-control datasets will be required to understand fully the effect of E318G on Alzheimer's disease status.

Modelling assistive technology adoption for people with dementia.

PURPOSE: Assistive technologies have been identified as a potential solution for the provision of elderly care. Such technologies have in general the capacity to enhance the quality of life and increase the level of independence among their users. Nevertheless, the acceptance of these technologies is crucial to their success. Generally speaking, the elderly are not well-disposed to technologies and have limited experience; these factors contribute towards limiting the widespread acceptance of technology. It is therefore important to evaluate the potential success of technologies prior to their deployment. MATERIALS AND METHODS: The research described in this paper builds upon our previous work on modelling adoption of assistive technology, in the form of cognitive prosthetics such as reminder apps and aims at identifying a refined sub-set of features which offer improved accuracy in predicting technology adoption. Consequently, in this paper, an adoption model is built using a set of features extracted from a user's background to minimise the likelihood of non-adoption. The work is based on analysis of data from the Cache County Study on Memory and Aging (CCSMA) with 31 features covering a range of age, gender, education and details of health condition. In the process of modelling adoption, feature selection and feature reduction is carried out followed by identifying the best classification models. FINDINGS: With the reduced set of labelled features the technology adoption model built achieved an average prediction accuracy of 92.48% when tested on 173 participants. CONCLUSIONS: We conclude that modelling user adoption from a range of parameters such as physical, environmental and social perspectives is beneficial in recommending a technology to a particular user based on their profile.

Family member deaths across adulthood predict Alzheimer's disease risk: The Cache County Study.

OBJECTIVES: Parental death during childhood, and offspring and spouse death during adulthood have individually been associated with faster cognitive decline and higher Alzheimer's disease (AD) risk in late life. However, the cumulative effect of childhood and adulthood family deaths on AD risk among different age cohorts has not been studied. METHODS: To examine these associations, this prospective cohort study uses a population-based sample of 4545 initially non-demented participants (56.7% female; age M = 75.0/SD = 6.9 years) observed at four triennial waves, linked with objective Utah Population Database data on cumulative mother, father, sibling, spouse, and offspring death experienced during childhood and adulthood. Cox regression modeled survival time from baseline interview to AD onset, as a function of family deaths during childhood or adulthood, among different age groups, along with gender and presence of ε4 allele at apolipoprotein E (APOE) polymorphic genetic locus. RESULTS: Age group significantly moderated the relationship between family death and AD; among persons aged 65-69 years at baseline (children of the Great Depression), those exposed to 3-4 deaths and 5+ deaths during adulthood exhibited a doubling of AD risk (adjusted hazard ratio, aHR = 2.25, p = .038, and aHR = 2.72, p = .029), while among persons aged 80 years and older, those exposed to 3-4 deaths during adulthood exhibited lower AD risk (HR = 0.539, p = 0.014). In a combined model of childhood and adulthood deaths, these findings persisted. CONCLUSIONS: Results suggest a cohort effect in the link between family member deaths during adulthood and AD risk later in life.

Closer caregiver and care-recipient relationships predict lower informal costs of dementia care: The Cache County Dementia Progression Study.

INTRODUCTION: Identifying factors associated with lower dementia care costs is essential. We examined whether two caregiver factors were associated with lower costs of informal care. METHODS: A total of 271 care dyads of the Cache County Dementia Study were included. Estimates of informal costs were based on caregiver reports of time spent in care-related activities and inflation-adjusted 2012 Utah median hourly wages. Caregiver coping and emotional closeness with the care-recipient were assessed using the Ways of Coping Checklist-Revised and Relationship Closeness Scale, respectively. RESULTS: Higher closeness was associated with 24% lower costs (expß = 0.763 [95% confidence interval: 0.583-0.999]) in linear mixed models controlling for demographics and baseline dementia severity and duration. Problem-focused coping was not associated with informal costs (P = .354). DISCUSSION: Caregiver closeness, a potentially modifiable factor, predicted lower dementia informal care costs over time. Future studies examining the care environment in closer dyads may identify specific care-related behaviors or strategies that are associated with lower costs.

Depression and antidepressant use moderate association between widowhood and Alzheimer's disease.

OBJECTIVE: In recent decades, biological evidence has implicated chronic stress in the etiology of Alzheimer's disease (AD). As a result, the relationship between widowhood, one of the most stressful life events, and AD has also received attention. This study extends this literature by investigating whether depression, which may indicate proneness to distress, and antidepressant use, which can protect against hippocampal shrinkage, moderate the relationship between widowhood and increased risk for AD. METHODS: To investigate this, this study utilized data from the Cache County Memory Study, a large population-based epidemiological study of AD, and the Utah Population Database, one of the world's foremost linked genealogical databases, to regress AD on the interaction between widowhood and history of depression and antidepressant use. RESULTS: In Cox regression analyses, history of depression and antidepressant use moderated the association between widowhood and AD (p = 0.007 and p = 0.006, respectively), in that widowhood was associated with 73% and 94% increased hazard of AD among those reporting depression (hazard ratio [HR] = 1.73, 95% confidence interval [CI]: 1.001 to 2.99) and those reporting antidepressant use (HR = 1.94, 95% CI: 1.13 to 3.33). A significant three-way interaction between widowhood, depression, and antidepressant use was also found (p = 0.02), showing depression to moderate the association between widowhood and AD only among those not using antidepressants (p = 0.02). CONCLUSIONS: These findings advance clinical and scientific knowledge concerning the effects of widowhood on risk for AD and underscore the importance of depression and antidepressant use in understanding vulnerability to and protection from these effects.

Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study.

OBJECTIVE: Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group. METHODS: We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating sum of boxes scores over time. We then used bias-corrected multinomial logistic regression to model baseline predictors of latent class membership. We constructed receiver operating characteristic curves to demonstrate relative predictive utility of successive sets of predictors. RESULTS: We fit four latent classes; class 1 was the largest (72%) and had the slowest progression. Classes 2 (8%), 3 (11%), and 4 (8%) had more rapid worsening. In univariate analyses, longer dementia duration, presence of psychosis, and worse baseline MMSE and Clinical Dementia Rating sum of boxes were associated with membership in class 2, relative to class 1. Lower education was associated with membership in class 3. In the multivariate model, only MMSE remained a statistically significant predictor of class membership. Receiver operating characteristic areas under the curve were 0.98, 0.88, and 0.67, for classes 2, 3, and 4 relative to class 1. CONCLUSIONS: Heterogeneity in AD course can be usefully characterized using growth mixture models. The majority belonged to a class characterized by slower decline than is typically reported in clinical samples. Class membership could be predicted using baseline covariates. Further study may advance our prediction of AD course at the population level and in turn shed light on the pathophysiology of progression.

Dementia caregivers' coping strategies and their relationship to health and well-being: the Cache County Study.

OBJECTIVES: Prior research identifies that psychological outcomes among dementia caregivers are associated with their use of coping strategies. Few studies have tested the association of coping and health longitudinally. METHOD: This study examined factors associated with the use of coping strategies over time and their associations with physical and mental health outcomes in a population-based sample of 226 dementia caregivers in Cache County, Utah, USA. Caregivers annually completed the Ways of Coping Checklist-Revised, the Beck Anxiety Inventory, and a health interview. Care-recipient cognitive and functional abilities were obtained using the Mini-Mental State Exam and the Clinical Dementia Rating. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. RESULTS: Caregivers most frequently identified providing care as a problem (37.6%). Linear mixed models of caregiver coping strategies found that the use of most strategies were stable except for increasing Avoidance among adult child caregivers (ß = 0.14, p = 0.048). On average, increased Wishful Thinking (ß = 2.48, p < 0.001) or Blames Self (ß = 1.06, p = 0.002) was associated with higher anxiety scores. Increased use of Blames Others among males (interaction, ß = 0.28, p = 0.02) and greater use of Wishful Thinking among younger caregivers (interaction, ß = -0.01, p = 0.01) were associated with more caregiver health conditions. Coping strategies were not associated with change in anxiety or health conditions over time. CONCLUSION: Our results emphasize the importance of caregiver coping strategies on caregiver health and well-being and may identify subgroups of persons at risk for worse outcomes.

Dementia severity and the longitudinal costs of informal care in the Cache County population.

BACKGROUND: Dementia costs are critical for influencing healthcare policy, but limited longitudinal information exists. We examined longitudinal informal care costs of dementia in a population-based sample. METHODS: Data from the Cache County Study included dementia onset, duration, and severity assessed by the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and Neuropsychiatric Inventory (NPI). Informal costs of daily care (COC) was estimated based on median Utah wages. Mixed models estimated the relationship between severity and longitudinal COC in separate models for MMSE and CDR. RESULTS: Two hundred and eighty-seven subjects (53% female, mean (standard deviation) age was 82.3 (5.9) years) participated. Overall COC increased by 18% per year. COC was 6% lower per MMSE-point increase and compared with very mild dementia, COC increased over twofold for mild, fivefold for moderate, and sixfold for severe dementia on the CDR. CONCLUSIONS: Greater dementia severity predicted higher costs. Disease management strategies addressing dementia progression may curb costs.

Population substructure in Cache County, Utah: the Cache County study.

BACKGROUND: Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: Our findings show that the Cache County study is similar in ethnic diversity to the self-reported "Whites" in the ADNI sample and less homogenous than the HapMap CEU population. CONCLUSIONS: We conclude that the Cache County study is genetically representative of the general European American population in the USA and is an appropriate population for conducting broadly applicable genetic studies.

Mitochondrial genomic variation associated with higher mitochondrial copy number: the Cache County Study on Memory Health and Aging.

BACKGROUND: The mitochondria are essential organelles and are the location of cellular respiration, which is responsible for the majority of ATP production. Each cell contains multiple mitochondria, and each mitochondrion contains multiple copies of its own circular genome. The ratio of mitochondrial genomes to nuclear genomes is referred to as mitochondrial copy number. Decreases in mitochondrial copy number are known to occur in many tissues as people age, and in certain diseases. The regulation of mitochondrial copy number by nuclear genes has been studied extensively. While mitochondrial variation has been associated with longevity and some of the diseases known to have reduced mitochondrial copy number, the role that the mitochondrial genome itself has in regulating mitochondrial copy number remains poorly understood. RESULTS: We analyzed the complete mitochondrial genomes from 1007 individuals randomly selected from the Cache County Study on Memory Health and Aging utilizing the inferred evolutionary history of the mitochondrial haplotypes present in our dataset to identify sequence variation and mitochondrial haplotypes associated with changes in mitochondrial copy number. Three variants belonging to mitochondrial haplogroups U5A1 and T2 were significantly associated with higher mitochondrial copy number in our dataset. CONCLUSIONS: We identified three variants associated with higher mitochondrial copy number and suggest several hypotheses for how these variants influence mitochondrial copy number by interacting with known regulators of mitochondrial copy number. Our results are the first to report sequence variation in the mitochondrial genome that causes changes in mitochondrial copy number. The identification of these variants that increase mtDNA copy number has important implications in understanding the pathological processes that underlie these phenotypes.

Impact of offspring death on cognitive health in late life: the Cache County study.

OBJECTIVE: Experiencing the death of a child is associated with negative short-term mental health consequences, but less is known about cognitive outcomes and whether such associations extend to late life. We tested the hypothesis that experiencing an offspring death (OD) is associated with an increased rate of cognitive decline in late life. METHODS: This population-based longitudinal study observed four cognitive statuses spaced 3-4 years apart, linked to an extensive database containing objective genealogic and vital statistics data. Home visits were conducted with 3,174 residents of a rural county in northern Utah, initially without dementia, aged 65-105. Cognitive status was measured with the Modified Mini-Mental State Exam at baseline and at 3-, 7-, and 10-year follow-ups. OD was obtained from the Utah Population Database, which contains statewide birth and death records. RESULTS: In linear mixed models, controlling for age, gender, education, and apolipoprotein E status, subjects who experienced OD while younger than age 31 years experienced a significantly faster rate of cognitive decline in late life, but only if they had an ε4 allele. Reclassifying all OD (regardless of age) according to subsequent birth of another child, OD was only related to faster cognitive decline when there were no subsequent births. CONCLUSION: Experiencing OD in early adulthood has a long-term association with cognitive functioning in late life, with a gene-environment interaction at the apolipoprotein E locus. Subsequent birth of another child attenuates this association.

Subjective stressors moderate effectiveness of a multi-component, multi-site intervention on caregiver depression and burden.

OBJECTIVES: The present study assessed whether caregiving contextual factors moderated outcomes of a caregiver intervention. METHODS: Extant data from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) II study, a randomized-control trial of a multi-component, multi-site intervention for dementia caregivers was utilized. 498 caregivers {83.1% women; mean [standard deviation (SD)] age = 60.3 (13.1)}, and their care recipients [58.6% women, mean (SD) age = 78.5 (9.6)] were randomly assigned to intervention or control group. Multiple regression was used to regress Center for Epidemiological Studies of Depression Scale (CES-D) and Zarit burden scores on the interaction between group membership and various factors reflecting the caregiving context. RESULTS: Lower follow-up CES-D scores in the intervention group were found only for those: in the fourth quartile of baseline CES-D (ß = -0.13, p = 0.05; overall interaction p = 0.009), with high Revised Memory and Behavior Problems Checklist (RMBPC) stress (ß = -0.16, p = 0.03) and with a home health aide (ß = -0.29, p = 0.009). Diminished burden was found in the intervention group only for the following: those in the fourth quartile of baseline burden (ß = -0.16, p = 0.01), and in the fourth quartile (ß = -0.16, p = 0.05) of Mini Mental State Examination, and with high RMBPC stress (ß = -0.18, p = 0.008), with a trend for diminished burden among those with a paid homemaker (ß = -0.19, p = 0.075). CONCLUSION: Results suggest greater intervention efficacy among caregivers experiencing subjective stress.

The association of traumatic brain injury with rate of progression of cognitive and functional impairment in a population-based cohort of Alzheimer's disease: the Cache County Dementia Progression Study.

BACKGROUND: There is limited research on factors that influence the rate of progression in Alzheimer's disease (AD). A history of traumatic brain injury (TBI) is associated with an increased risk for AD, but its role on the rate of dementia progression after the onset of AD has not been examined. METHODS: A population-based cohort of 325 persons with incident AD was followed for up to 11 years. The sample was 65% female with a mean (SD) age of dementia onset = 84.4 (6.4) years. History of TBI was categorized as number, severity (with or without loss of consciousness), and timing in relation to dementia onset (within ten years or more than ten years). Cognition was assessed by the Consortium to Establish a Registry of AD battery, and functional ability was assessed by the Clinical Dementia Rating Sum of Boxes. RESULTS: In linear mixed models, a history of TBI within ten years of onset showed faster progression of functional impairment (LR x2 = 10.27, p = 0.006), while those with TBI more than ten years before dementia onset had higher scores on a measure of list learning (ß = 1.61, p = 0.003) and semantic memory (ß = 0.75, p = 0.0035). CONCLUSIONS: History of TBI and its recency may be a useful factor to predict functional progression in the course of AD.

Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: the Cache County Dementia Progression Study.

BACKGROUND: Single-nucleotide polymorphisms (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 associated with higher cerebrospinal fluid (CSF) tau levels in samples from the Knight Alzheimer's Disease Research Center at Washington University (WU) and Alzheimer's Disease Neuroimaging Initiative (ADNI). In these same samples, these SNPs were also associated with faster functional decline, or progression of Alzheimer's disease (AD) as measured by the Clinical Dementia Rating sum of boxes scores (CDR-sb). We attempted to validate the latter association in an independent, population-based sample of incident AD cases from the Cache County Dementia Progression Study (DPS). METHODS: All 92 AD cases from the DPS with a global CDR-sb ≤1 (mild) at initial clinical assessment who were later assessed on CDR-sb data on at least two other time points were genotyped at the two SNPs of interest (rs1868402 and rs3785883). We used linear mixed models to estimate associations between these SNPs and CDR-sb trajectory. All analyses were performed using Proc Mixed in SAS. RESULTS: Although we observed no association between rs3785883 or rs1868402 alone and change in CDR-sb (P > .10), there was a significant association between a combined genotype model and change in CDR-sb: carriers of the high-risk genotypes at both loci progressed >2.9 times faster than noncarriers (P = .015). When data from DPS were combined with previously published data from WU and ADNI, change in CDR-sb was 30% faster for each copy of the high-risk allele at rs3785883 (P = .0082) and carriers of both high-risk genotypes at both loci progressed 6 times faster (P < .0001) than all others combined. CONCLUSIONS: We replicate a previous report by Cruchaga et al that specific variations in rs3785883 and rs1868402 are associated with accelerated progression of AD. Further characterization of this association will provide a better understanding of how genetic factors influence the rate of progression of AD and could provide novel insights into preventative and therapeutic strategies.

Caregiver coping strategies predict cognitive and functional decline in dementia: the Cache County Dementia Progression Study.

OBJECTIVES: Few longitudinal studies have studied the influence of the care environment on the clinical progression of dementia. We examined whether caregiver coping strategies predict dementia progression in a population-based sample. DESIGN: Longitudinal, prospective cohort study. SETTING: Cache County (Utah) population. PARTICIPANTS: A total of 226 persons with dementia, and their caregivers, were assessed semiannually for up to 6 years. MEASUREMENTS: Ways of Coping Checklist-Revised, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). RESULTS: Mean (SD) age of dementia onset in persons with dementia was 82.11 (5.84) years and mean caregiver age was 67.41 (13.95) years. Mean (SD) follow-up was 1.65 (1.63) years from baseline. In univariate linear mixed-effects models, increasing use of problem-focused and counting blessings by caregivers was associated with slower patient worsening on the MMSE. Problem-focused coping, seeking social support, and wishful thinking were associated with slower Clinical Dementia Rating Scale sum of boxes (CDR-sb) worsening. Considering covariates, increasing use of problem-focused coping was associated with 0.70 points per year less worsening on the MMSE and 0.55 points per year less worsening on the CDR-sb. Compared with no use, the "regular" use of this strategy was associated with 2 points per year slower worsening on the MMSE and 1.65 points per year slower worsening on the CDR-sb. CONCLUSIONS: Caregiver coping strategies are associated with slower dementia progression. Developing interventions that target these strategies may benefit dementia patients.

Baseline disability in activities of daily living predicts dementia risk even after controlling for baseline global cognitive ability and depressive symptoms.

OBJECTIVES: Late-life disability in activities of daily living (ADL) is theorized to be driven by underlying cognitive and/or physical impairment, interacting with psychological and environmental factors. Although we expect that cognitive deficits would explain associations between ADL disability and dementia risk, the current study examined ADL as a predictor of future dementia after controlling for global cognitive status. METHODS: The population-based Cache County Memory Study (N = 3547) assessed individuals in four triennial waves (average age 74.9 years, years of education 13.36 years; 57.9% were women). Cox proportional hazards regression models assessed whether baseline ADL disability (presence of 2+ Instrumental ADL and/or 1+ Personal ADL) predicted incident dementia after controlling for APOE status, gender, age, baseline cognitive ability (Modified Mini-mental State Exam, 3MS-R; adjusted for education level), and baseline depressive symptoms (Diagnostic Interview Schedule). RESULTS: Over the course of study, 571 cases of incident dementia were identified through in-depth cognitive assessment, ending in expert consensus diagnosis. Results from Cox models suggest that ADL disability is a statistically significant predictor of incident dementia (adjusted hazard ratio = 1.83, p < 0.001), even after controlling for covariates. CONCLUSIONS: Findings suggest that ADL disability offers unique contributions in risk for incident dementia, even after controlling for global cognitive status. We discuss how physical impairment and executive function may play important roles in this relationship, and how ADL is useful, not just a diagnostic tool at, or after dementia onset, but also as a risk factor for future dementia, even in individuals not impaired on global cognitive tests.