Malnutrition and neuropsychiatric symptoms in dementia: the Cache County Dementia Progression Study.

OBJECTIVES: Among people with dementia, poor nutritional status has been associated with worse cognitive and functional decline, but few studies have examined its association with neuropsychiatric symptoms (NPS). We examined this topic in a population-based sample of persons with dementia. DESIGN: Longitudinal, observational cohort study. SETTING: Community. PARTICIPANTS: Two hundred ninety-two persons with dementia (71.9% Alzheimer's disease, 56.2% women) were followed up to 6 years. MEASUREMENTS: We used a modified Mini-Nutritional Assessment (mMNA) and the Neuropsychiatric Inventory (NPI) to evaluate nutritional status and NPS, respectively. Individual linear mixed effects models examined the associations between time-varying mMNA total score or clinical categories (malnourishment, risk for malnourishment, or well-nourished) and NPI total score (excluding appetite domain) or NPI individual domain or cluster (e.g. psychosis) scores. Covariates tested were dementia onset age, type, and duration, medical comorbidities, sex, apolipoprotein E (APOE) genotype, and education. RESULTS: Compared to the well-nourished, those at risk for malnourishment and those malnourished had higher total NPI scores [b (95% CI) = 1.76 (0.04, 3.48) or 3.20 (0.62, 5.78), respectively], controlling for significant covariates. Higher mMNA total score (better nutritional status) was associated with lower total NPI [b (95% CI) = -0.58 (-0.86, -0.29)] and lower domain scores for psychosis [b (95% CI) = -0.08 (-0.16, .004)], depression [b (95% CI = -0.11 (-0.16, -0.05], and apathy [b (95% CI = -0.19 (-0.28, -0.11)]. CONCLUSIONS: Worse nutritional status is associated with more severe NPS. Dietary or behavioral interventions to prevent malnutrition may be beneficial for persons with dementia.

How good are medical and death records for identifying dementia?

INTRODUCTION: Retrospective studies using administrative data may be an efficient way to assess risk factors for dementia if diagnostic accuracy is known. METHODS: Within-individual clinical diagnoses of Alzheimer's disease (AD) and all-cause dementia in ambulatory (outpatient) surgery, inpatient, Medicare administrative records and death certificates were compared with research diagnoses among participants of Cache County Study on Memory, Health, and Aging (CCSMHA) (1995-2008, N = 5092). RESULTS: Combining all sources of clinical health data increased sensitivity for identifying all-cause dementia (71%) and AD (48%), while maintaining relatively high specificity (81% and 93%, respectively). Medicare claims had the highest sensitivity for case identification (57% and 40%, respectively). DISCUSSION: Administrative health data may provide a less accurate method than a research evaluation for identifying individuals with dementing disease, but accuracy is improved by combining health data sources. Assessing all-cause dementia versus a specific cause of dementia such as AD will result in increased sensitivity, but at a cost to specificity.

Neuropsychiatric Symptoms as Risk Factors for Cognitive Decline in Clinically Normal Older Adults: The Cache County Study.

INTRODUCTION: There has been considerable progress in identifying early cognitive and biomarker predictors of Alzheimer's disease (AD). Neuropsychiatric symptoms (NPS) are common in AD and appear to predict progression after the onset of mild cognitive impairment or dementia. OBJECTIVES: The objective of the study is to examine the relationship between NPS in clinically normal older adults and subsequent cognitive decline in a population-based sample. METHODS: The Cache County Study on Memory in Aging consists of a population-based sample of 5,092 older adults. We identified 470 clinically normal adults who were followed for an average period of 5.73 years. NPS were evaluated at the baseline clinical assessment using the Neuropsychiatric Inventory (NPI). NPI domain scores were quantified as the product of frequency X severity in individual NPI domains, and then summed for the NPI-Total. Neuropsychological measures were collected at baseline and at each subsequent follow-up wave. Linear mixed-effects models assessed the association of NPI-Total, NPI-Depression, and NPI-Anxiety scores (obtained at baseline) on longitudinal change in neuropsychological performance, controlling for age, sex, and education. RESULTS: Baseline NPI-Total score was associated with a more rapid rate of decline in word list memory, praxis recall, and animal fluency. Baseline NPI-Depression was not associated with later decline on any of the cognitive tests, while baseline NPI-Anxiety was associated with decline in Symbol Digit Modality. CONCLUSION: In conclusion, among clinically normal older adults derived from this population-based study, total burden of NPS was associated with longitudinal cognitive decline. These results add to the evidence that NPS are risk factors for or clinical indicators of preclinical dementia syndrome. Our study was an exploratory study and we did not control for multiple comparisons.

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.

Caregiver-Care Recipient Relationship Closeness is Associated With Neuropsychiatric Symptoms in Dementia.

OBJECTIVE: Closer caregiver-care recipient (CG-CR) relationships are associated with better cognitive and functional abilities, activities of daily living (in persons with dementia), and lower informal care costs. METHODS: Due to the difficulty in treating neuropsychiatric symptoms (NPSs) and their detrimental effects on caregivers and care recipients, we examined whether closeness of CG-CR relationships was associated with overall NPS severity or with specific NPS symptom domains in care recipients. In a longitudinal population-based study in Cache County, Utah, the 12-item Neuropsychiatric Inventory (NPI-12) was assessed in 300 CG-CR dyads. Caregivers reported current relationship closeness using the Whitlatch Relationship Closeness Scale. Linear mixed models examined associations between CG-CR closeness and NPI-12 total score or selected symptom domains over time (observation period: 2002-2012). RESULTS: In unadjusted linear mixed models, higher closeness scores were associated with a five-point lower NPI-12 score and a one-point lesser increase in NPI-12 per year. NPI scores also showed lower affective cluster scores (two points) and lesser increase in psychosis cluster (approximately 0.5 points per year) and agitation/aggression (0.16 points per year) for each unit increase in closeness. When controlling for NPI caregiver distress, associations between closeness and NPSs diminished to a 0.5-point lesser increase in total NPI-12 score per year. Adjusted models for NPI domains/clusters showed -0.32 points per year for the psychosis cluster, -0.11 points per year for agitation/aggression, and -0.67 overall for the affective cluster. CONCLUSION: Higher CG-CR closeness, a potentially modifiable factor, is associated with lower NPS severity and may provide a target for intervention.

Neuropsychiatric symptoms in severe dementia: Associations with specific cognitive domains the Cache County Dementia Progression Study.

OBJECTIVES: To examine the prevalence of neuropsychiatric symptoms (NPS) and cognitive correlates in severe dementia. METHODS: A population-based sample of 56 individuals with severe dementia (85.7% Alzheimer's type; 67.9% female) were assessed with the Severe Cognitive Impairment Profile (SCIP) and the Neuropsychiatric Inventory (NPI). Descriptive statistics displayed the frequency of NPS and bivariate and multiple regression analyses examined the associations between cognitive domains on the SCIP and NPS total, domain, and cluster scores. RESULTS: NPS were common in severe dementia with 98% of the sample exhibiting at least one symptom. Most common were delusions, apathy, agitation/aggression, and aberrant motor behavior, affecting 50% or more of participants. SCIP comportment was significantly associated with NPI total score and apathy (r = -.350 and -.292, respectively). All SCIP domains except for arithmetic, visuospatial, comportment, and motor behavior were significantly associated with agitation/aggression (r = -.285 to -.350). These associations remained in individual multiple regression models. CONCLUSION: In severe dementia, impairment in specific cognitive domains was associated with more severe NPS. Environmental manipulations to reduce processing demands in persons with severe dementia may be a useful strategy to target agitation and aggressive behaviors.

Nutritional Status is Associated With Severe Dementia and Mortality: The Cache County Dementia Progression Study.

PURPOSE: Studies have reported faster cognitive/functional decline in persons with dementia (PWD) with malnutrition. We investigated whether baseline nutritional status predicted severe dementia and mortality in a population-based sample. PATIENTS: A maximum of 300 PWD were assessed annually for up to 8.6 years. METHODS: Nutritional status was assessed using a modified Mini-Nutritional Assessment (mMNA). Severe dementia was defined as: "severe" rating on the Clinical Dementia Rating or Mini-Mental State Examination score ≤10. Using Cox proportional hazards models, we examined the association between baseline mMNA score (or its subcomponents) with each outcome. Covariates included demographics; dementia onset age, type, and duration; APOE genotype; and residency with caregiver. RESULTS: Compared with "well-nourished," "malnourished" PWD had 3-4 times the hazard of severe dementia [hazard ratio (HR), 4.31; P=0.014] and death (HR, 3.04; P<0.001). Those "at risk for malnutrition" had twice the hazard of severe dementia (HR, 1.98; P=0.064) and 1.5 times the hazard of death (HR, 1.46; P=0.015). mMNA subcomponents of food group intake, weight loss, body mass index, mobility, health status, protein consumption, and mid-arm circumference predicted one or both outcomes. CONCLUSIONS: Nutritional status is an important predictor of clinical outcomes in dementia and may provide an avenue for intervention.

Use of FDA approved medications for Alzheimer's disease in mild dementia is associated with reduced informal costs of care.

ABSTRACTBackground:The use of FDA approved medications for Alzheimer's disease [AD; FDAAMAD; (cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists)] has been associated with symptomatic benefit with a reduction in formal (paid services) and total costs of care (formal and informal costs). We examined the use of these medications and their association with informal costs in persons with dementia. METHOD: Two hundred eighty participants (53% female, 72% AD) from the longitudinal, population-based Dementia Progression Study in Cache County, Utah (USA) were followed up to ten years. Mean (SD) age at baseline was 85.6 (5.5) years. Informal costs (expressed in 2015 dollars) were calculated using the replacement cost method (hours of care multiplied by the median wage in Utah in the visit year) and adjusted for inflation using the Medical Consumer Price Index. Generalized Estimating Equations with a gamma log-link function were used to examine the longitudinal association between use of FDAAMAD and informal costs. RESULTS: The daily informal cost for each participant at baseline ranged from $0 to $318.12, with the sample median of $9.40. Within the entire sample, use of FDAAMAD was not significantly associated with informal costs (expß = 0.73, p = 0.060). In analyses restricted to participants with mild dementia at baseline (N = 222), use of FDAAMAD was associated with 32% lower costs (expß = 0.68, p = 0.038). CONCLUSIONS: Use of FDAAMAD was associated with lower informal care costs in those with mild dementia only.

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.

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.

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.

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.

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.

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.

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.

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.