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Objectives: To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD).Design: Survival analysis of time to dementia, AD, or VaD onset.Setting: Population-based study.Participants: 230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years.Measurements: The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-squared statistics, t-tests, and Cox proportional hazard ratios were used to assess associations.Results: The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower Mini-Mental State Examination, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, whereas hallucinations were a risk factor for VaD.Conclusions: These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD. [ABSTRACT FROM AUTHOR]

Objective: We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. Participants and Design: In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment, Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. Results: Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. Conclusion: High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly. [ABSTRACT FROM AUTHOR]

Objective To investigate the probability of individual neuropsychiatric symptoms in dementia patients as a function of eight risk factors. Methods In the Cache County Study, we administered the Neuropsychiatric Inventory (NPI) to 328 dementia patients at baseline. Approximately 18 months later, we re-administered the NPI to 184 participants available for follow-up. Generalized estimating equation methods were used to model the probability of individual neuropsychiatric symptoms as a function of: gender, age, education, dementia type and severity, APOE status, time of observation, and general medical health. Results Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.31–3.76] and delusions (OR 2.15, CI 1.22–3.78), but older persons of both sexes showed less tendency toward anxiety. Dementia severity increased the tendency toward hallucinations and agitation (OR 2.42, CI 1.81–3.23) and decreased risk of depression. Positive APOE ℇ4 status increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05–3.22). Among dementia diagnoses, those with Alzheimer's disease showed decreased tendency toward agitation (OR 0.58, CI 0.35–0.95), depression (OR 0.56, CI 0.33–0.96) and disinhibition (OR 0.46, CI 0.24–0.88). Later time of observation increased risk of aberrant motor behavior and delusions, and more serious medical comorbidity increased risk of, agitation, irritability, disinhibition, and aberrant motor behavior. Conclusions Gender, age, dementia severity, APOE ℇ4, dementia diagnosis, time of observation, and general medical health appear to influence the occurrence of individual neuropsychiatric symptoms. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: White matter burden and medial temporal atrophy are associated with cognitive health. A large epidemiological database, such as the Cache County Memory Study (CCMS), can provide additional insight into how visual clinical ratings of brain structural integrity predict cognition in older adults., Method: We used the Scheltens Ratings Scale to quantify white matter lesion burden and medial temporal atrophy in the CCMS sample to determine if these qualitative markers are predictive of memory function. We performed clinical ratings of MRI scans across two ascertainment periods among 187 community-dwelling older adults and correlated these ratings with MMSE, CERAD memory performance, and general cognitive ability., Results: Higher Scheltens ratings measuring white matter and basal ganglia hyperintensities were associated with lower memory performance (r = 0.21). The strongest correlations were observed between medial temporal atrophy and general cognition performance (r = 0.32)., Conclusions: The current findings support previous research that the integrity of different regions of the brain correlate to function in a meaningful way., Competing Interests: There are no conflicts of interest., (© The Author(s) 2022.)

The brain reserve hypothesis has been posited as being one important mediating factor for developing dementia, especially Alzheimer's disease (AD). Evidence for this hypothesis is mixed though different methodologies have made these findings difficult to interpret. We examined imaging data from a large cohort (N=194) of mixed dementia patients and controls, 65years old and older from the Cache County, Utah Study of Memory and Aging for evidence of the brain reserve hypothesis using total intracranial volume (TICV) as a quantitative measure of pre-morbid brain size and a vicarious indicator of reserve. A broader spectrum of non-demented elderly control subjects from previous studies was also included for comparison (N=423). In addition, non-parametric Classification and Regression Tree (CART) analyses were performed to model group heterogeneity and identify any subgroups of patients where TICV might be an important predictor of dementia. Parametrically, no main effect was found for TICV when predicting a dementia diagnosis; however, the CART analysis did reveal important TICV subgroups, including a sex differential wherein ε4 APOE allele presence in males and low TICV predicted AD classification. TICV, APOE, and other potential mediator/moderator variables are discussed in the context of the brain reserve hypothesis., (Copyright © 2010. Published by Elsevier B.V.)

Background: It is unclear whether vascular dementia (VaD) has a cognitive prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer's dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be differentiated from prodromal AD, we examined neuropsychological test performance of participants in a nested case-control study within a population-based cohort aged 65 or older., Methods: Participants (n = 485) were identified from the Cache County Study, a large population-based study of aging and dementia. After an average of 3 years of follow-up, a total of 62 incident dementia cases were identified (14 VaD, 48 AD). We identified a number of neuropsychological tests (executive and memory) that discriminated between diagnosed VaD and AD cases. Multivariate analyses sought to differentiate between these same groups 3 years before clinical diagnosis., Results: The Consortium to Establish a Registry for Alzheimer's Disease Word List Recognition Test correct recognition of foils (mean difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001) differentiated VaD from AD cases after adjustment for age, sex, education, and dementia severity. Three years before dementia diagnosis, word list recognition ("no" responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and "yes" responses mean difference, -1.14; 95% CI, -2.14 to -0.13; p < 0.03) discriminated between prodromal VaD and AD., Conclusion: These results suggest that VaD has a prodromal syndrome, the cognitive features of which are distinguishable from the cognitive prodrome of AD.

Objective: To examine the relative risk and population attributable risk (PAR) of death with dementia of varying type and severity and other risk factors in a population of exceptional longevity., Methods: Deaths were monitored over 5 years using vital statistics records and newspaper obituaries in 355 individuals with prevalent dementia and 4,328 without in Cache County, UT. Mean age was 83.3 (SD 7.0) years with dementia and 73.7 (SD 6.8) years without. History of coronary artery disease, hypertension, diabetes, and other life-shortening illness was ascertained from interviews., Results: Death certificates implicated dementia as an important cause of death, but other data suggested a stronger association. Adjusted Cox relative hazard and PAR of death were higher with dementia than with any other illness studied. Relative hazard of death with dementia was highest at ages 65 to 74, but the high prevalence of dementia after age 85 resulted in 27% PAR among the oldest old. Mortality increased substantially with severity of dementia. Alzheimer disease shortened survival time most dramatically in younger participants, but vascular dementia posed a greater mortality risk among the oldest old., Conclusion: In this population, dementia was the strongest predictor of mortality, with a risk two to three times those of other life-shortening illnesses.

Objective: We investigated the frequency and inter-relationship of neuropsychiatric disturbances in a population sample of persons suffering from Alzheimer's disease (AD)., Method: Screening 5,092 elderly residents (90% of the population aged 65 and older) of Cache County, Utah, for dementia, we identified 198 persons with AD using a comprehensive neuropsychiatric examination protocol. This examination included the Neuropsychiatric Inventory (NPI), a widely used measure of dementia-associated neuropsychiatric disturbances., Results: Overall, 60% of individuals with AD reported one or more neuropsychiatric symptoms. A latent class analysis revealed that these participants could be classified into three groups (classes) based on their neuropsychiatric symptom profile. The largest class included cases with no neuropsychiatric symptoms (40%) or with a mono-symptomatic disturbance (19%). A second class (28%) exhibited a predominantly affective syndrome, while a third class (13%) had a psychotic syndrome., Conclusion: Data from this first US population-based study of AD-associated neuropsychiatric disturbances suggest that a significant majority of persons with AD suffer from one or more neuropsychiatric disturbance. Based on phenomenological study, the spectrum of neuropsychiatric symptoms in AD can be empirically classified into three groups: an affective syndrome, a psychotic syndrome and other neuropsychiatric disturbance. The biologic and predictive validity of this classification merits further investigation., (Copyright 2001 John Wiley & Sons, Ltd.)

Background: 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., Methods: 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.", Results: 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., Conclusions: 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.

Objective: The authors report findings from a study of 5,092 community residents who constituted 90% of the elderly resident population of Cache County, Utah., Method: The 5,092 participants, who were 65 years old or older, were screened for dementia. Based on the results of this screen, 1,002 participants (329 with dementia and 673 without dementia) underwent comprehensive neuropsychiatric examinations and were rated on the Neuropsychiatric Inventory, a widely used method for ascertainment and classification of dementia-associated mental and behavioral disturbances., Results: Of the 329 participants with dementia, 214 (65%) had Alzheimer's disease, 62 (19%) had vascular dementia, and 53 (16%) had another DSM-IV dementia diagnosis; 201 (61%) had exhibited one or more mental or behavioral disturbances in the past month. Apathy (27%), depression (24%), and agitation/aggression (24%) were the most common in participants with dementia. These disturbances were almost four times more common in participants with dementia than in those without. Only modest differences were observed in the prevalence of mental or behavioral disturbances in different types of dementia or at different stages of illness: participants with Alzheimer's disease were more likely to have delusions and less likely to have depression. Agitation/aggression and aberrant motor behavior were more common in participants with advanced dementia., Conclusions: On the basis of their findings in this large community population of elderly people, the authors conclude that a wide range of dementia-associated mental and behavioral disturbances afflict the majority of individuals with dementia. Because of their frequency and their adverse effects on patients and their caregivers, these disturbances should be ascertained and treated in all cases of dementia.

Objective: To examine the association between history of postmenopausal estrogen use and cognitive function in a large sample of nondemented community-dwelling older women., Setting: A community of older residents in Cache County, Utah., Participants: A total of 2338 nondemented women aged 65 and older., Measurements: All subjects were administered the Modified Mini-Mental State Examination (3MSE). Self-reported information on current and past use of estrogen after menopause was also obtained using a structured interview. Estrogen use was trichotomized as: no use, past use, and current use. Apolipoprotein E (APOE) genotype was determined and was dichotomized by the presence of an epsilon4 allele. A series of variance/covariance models was conducted with the 3MSE score as the dependent variable, first considering estrogen use alone, then adding, sequentially as covariates, education, age, health status, APOE genotype, current depression status, and history of head injury., Results: In the simplest bivariate model, the 3MSE means (and confidence intervals) were 92.1 (91.7-92.4), 93.5 (93.1-93.9), and 94.4 (94.0-94.7) for never-, past-, and current users, respectively. In the final model (R2 = 0.28), no use of estrogen replacement therapy (P = .006), lower education (P < .001), poorer perceived health status (P = .035), current depression (P = .014), and presence of at least one APOE epsilon4 allele (P < .001) each independently predicted lower 3MSE score. Both current and past estrogen users had significantly higher 3MSE scores than never-users (P = .0063 and P = .0096, respectively)., Conclusions: In this large community study, women who had used estrogen after menopause scored higher on the 3MSE. This finding remained, even after controlling for the effects of age, education, APOE genotype, and other variables that may affect cognition. These data support studies reporting a beneficial role of estrogen on cognition in postmenopausal women, particularly among current estrogen users.

Objective: To examine the concurrent validity of a newly developed telephone adaptation of the Modified Mini-Mental State Exam., Background: Longitudinal studies of cognition may be advantaged by availability of assessment instruments that can be used over the telephone, as well as in person., Method: Subjects were 263 noninstitutionalized elderly residents of a rural community in southern Idaho, aged 65 to 93, who had little or no cognitive difficulty. At an average interval of four weeks, we administered the Modified Mini-Mental State Exam (3MS) and the newly adapted Telephone Modified Mini-Mental State Exam (T3MS). Order of administration was randomly assigned., Results: Agreement between scores on the two instruments was good (r = 0.82, p < 0.001). When we applied various cutoff scores to the instruments, thereby generating assignments of individuals to "screen positive" and "screen negative" groups, the percent agreement in screening results ranged from 80% to 96% as we reduced the cutoff scores from 90 to 74 (100 points possible)., Conclusions: At least among subjects without major cognitive syndromes, the Telephone Modified Mini-Mental State Exam provides a reasonable substitute for the more costly in-person 3MS. The telephone instrument should now be tested over a broader range of cognitive abilities in order to assess its validity in more impaired subjects, e.g., by studying an institutionalized sample.

In the 1987 National Survey of Children the question was asked: "Was there ever a time when you were forced to have sex against your will, or were you raped?" Among White females, aged 18-22, those who answered yes (n = 41) and no (n = 400) were compared on a number of social-psychological and sexual variables that might be thought of as outcomes affected by having had coercive sexual experience(s). Those who reported being forced to have sexual intercourse, compared to those who did not, had more permissive attitudes about 16-17-year-olds having intercourse and a younger age of first voluntary sexual intercourse themselves. They also had lower internal locus of control and higher depression scores, and they needed and received more psychological help than those not reporting forced sexual intercourse. Dividing the forced sexual intercourse group (FSI) into those reporting FSI before versus after their first date, and those whose FSI was before versus after age 12, yielded essentially the same findings. Even in the presence of multivariate control variables. FSI experience remained a significant predictor of age at first voluntary sexual intercourse, locus of control, depression, and perceived need for psychological help. These analyses of national survey data support the clinical perspective that forced sexual intercourse causes or exacerbates various sexual and psychological problems.

Objective: To identify predictors of nonresponse in a community survey of cognitive status in the elderly., Design: Cross-sectional community survey with two stages of recruitment: an initial, less-intensive method, followed by a more aggressive approach that included face-to-face contact. Characteristics of initial nonresponders and responders were compared., Setting: A close-knit rural community with higher than usual proportions of elderly, especially the very old. Subjects were interviewed in their homes. Collateral informants were subsequently interviewed by telephone., Participants: Utah heads of household aged 75 and older who resided in a noninstitutionalized setting., Measurements: Mini-Mental State Examination (MMSE), Dementia Questionnaire, and an autobiographical risk factor and family history questionnaire provided measures for all independent variables. The dependent variable was status as initial responders or initial nonresponders., Results: An initial participation rate of 63% was achieved, but a final rate of 93% was achieved when initial nonresponders were contacted later face-to-face. MMSE score was significantly related to responder status when analyzed alone (beta = -.19, P = 0.02) and remained a significant predictor after adjusting for education and whether born in Cache County (beta = -.16, P = 0.041) or current drinking, diabetes, or "other" health problems (beta = -.18, P = 0.028). After controlling for the informant report of subject's problems with activities of daily living, MMSE score fell just below statistical significance (beta = -.16, P = 0.079)., Conclusions: Nonresponders in community surveys of the elderly appear to be disproportionately cognitively impaired. The increase in participation rates achieved after more persistent recruitment suggests that many initial nonresponders can still be recruited if intensive methods are used.