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Huibo Shao,
John C S Breitner,
Rachel A Whitmer,
Junmin Wang,
Kathleen Hayden,
Heidi Wengreen, Chris Corcoran,
Joann Tschanz,
Maria Norton,
Ron Munger,
Kathleen Welsh-Bohmer,
Peter P Zandi
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ABSTRACT: OBJECTIVES: Observational studies suggest reduced risk of Alzheimer disease (AD) in users of hormone therapy (HT), but trials show higher risk. We examined whether the association of HT with AD varies with timing or type of HT use. METHODS: Between 1995 and 2006, the population-based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT. During this interval, 176 women developed incident AD. Cox proportional hazard models evaluated the association of HT use with AD, overall and in relation to timing, duration of use, and type (opposed vs unopposed) of HT. RESULTS: Women who used any type of HT within 5 years of menopause had 30% less risk of AD (95% confidence interval 0.49-0.99), especially if use was for 10 or more years. By contrast, AD risk was not reduced among those who had initiated HT 5 or more years after menopause. Instead, rates were increased among those who began "opposed" estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline (adjusted hazard ratio 1.93; 95% confidence interval 0.94-3.96). This last hazard ratio was similar to the ratio of 2.05 reported in randomized trial participants assigned to opposed HT. CONCLUSIONS: Association of HT use and risk of AD may depend on timing of use. Although possibly beneficial if taken during a critical window near menopause, HT (especially opposed compounds) initiated in later life may be associated with increased risk. The relation of AD risk to timing and type of HT deserves further study.
Neurology 10/2012; · 8.31 Impact Factor
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ABSTRACT: OBJECTIVE: Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of older individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. METHODS: A total of 2665 non-demented participants of the Cache County Memory Study completed an SLE questionnaire at Wave 2 and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, and unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. RESULTS: Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the aforementioned associations. CONCLUSIONS: The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature. Copyright © 2012 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry 10/2012; · 2.42 Impact Factor
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ABSTRACT: Closer relationships between caregivers and care recipients with dementia are associated with positive outcomes for care recipients, but it is unclear if closeness is a risk or protective factor for the health and psychological wellbeing of caregivers. We examined 234 care dyads from the population-based Cache County Dementia Progression Study. Caregivers included spouses (49%) and adult offspring (51%). Care recipients mostly had dementia of the Alzheimer’s type (62%). Linear mixed models tested associations between relationship closeness at baseline or changes in closeness prior to versus after dementia onset, with baseline levels and changes over time in caregiver affect (Affect Balance Scale, ABS), depression (Beck Depression Inventory, BDI), and mental and physical health (components of the Short-Form Health Survey, SF-12). After controlling for demographic characteristics of the caregiver, number of caregiver health conditions, and characteristics of the care recipient (type of dementia, functional ability, and behavioral disturbances), we found that higher baseline closeness predicted higher baseline SF-12 mental health scores (better mental health) and lower depression. Higher baseline closeness also predicted greater worsening over time in ABS and SF-12 mental health. In addition, caregivers who reported a loss of closeness in their relationship with the care recipient from pre- to post-dementia displayed improved scores on ABS and SF-12 mental health, but worse SF-12 physical health over the course of the study. These results suggest that closeness and loss of closeness in the care dyad may be associated with both positive and adverse outcomes for caregivers, both cross-sectionally and over time.
Aging and Mental Health 05/2012; 16(6):699-711. · 1.37 Impact Factor
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Maria C Norton,
Ken R Smith,
Truls Østbye,
JoAnn T Tschanz,
Sarah Schwartz, Chris Corcoran,
John C S Breitner,
David C Steffens,
Ingmar Skoog,
Peter V Rabins,
Kathleen A Welsh-Bohmer
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ABSTRACT: Early parental death is associated with lifelong tendencies toward depression and chronic stress. We tested the hypothesis that early parental death is associated with higher risk for Alzheimer disease (AD) in offspring.
A population-based epidemiological study of dementia with detailed clinical evaluations, linked to one of the world's richest sources of objective genealogical and vital statistics data.
Home visits with residents of a rural county in northern Utah.
4,108 subjects, aged 65-105.
Multistage dementia ascertainment protocol implemented in four triennial waves, yielding expert consensus diagnoses of 570 participants with AD and 3,538 without dementia. Parental death dates, socioeconomic status, and parental remarriage after widowhood were obtained from the Utah Population Database, a large genealogical database linked to statewide birth and death records.
Mother's death during subject's adolescence was significantly associated with higher rate of AD in regression models that included age, gender, education, APOE genotype, and socioeconomic status. Father's death before subject age 5 showed a weaker association. In stratified analyses, associations were significant only when the widowed parent did not remarry. Parental death associations were not moderated by gender or APOE genotype. Findings were specific to AD and not found for non-AD dementia.
Parental death during childhood is associated with higher prevalence of AD, with different critical periods for father's versus mother's death, with strength of these associations attenuated by remarriage of the widowed parent.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 09/2011; 19(9):814-24. · 3.35 Impact Factor
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Katherine A Treiber,
Michelle C Carlson, Chris Corcoran,
Maria C Norton,
John C S Breitner,
Kathleen W Piercy,
Michael Scott Deberard,
David Stein,
Beth Foley,
Kathleen A Welsh-Bohmer,
Amber Frye,
Constantine G Lyketsos,
Joann T Tschanz
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ABSTRACT: To examine the association of engagement in cognitively stimulating activities with cognitive and functional decline in a population-based sample of incident Alzheimer's disease (AD).
After diagnosis, 187 participants (65% females) were followed semiannually for a mean 2.7 (SD = 0.4) years. Mean age and education were 84.6 (SD = 5.8) and 13.2 (SD = 2.9) years. Caregivers enumerated cognitively stimulating leisure activities via the Lifestyle Activities Questionnaire. Cognition was assessed using the Mini-Mental State Examination and functional ability via the Clinical Dementia Rating sum of boxes. Linear mixed models tested the association between stimulating activities and change over time in each outcome. Covariates were demographic factors, estimated premorbid IQ, presence/absence of the APOE ε4 allele, duration of dementia, level of physical activity, and general health.
At initial assessment, 87% of participants were engaged in one or more stimulating activities, with mean (SD) activities = 4.0 (3.0). This number declined to 2.4 (2.0) at the final visit. There was a statistical interaction between dementia duration and number of activities in predicting rate of cognitive decline (p = .02) and overall functional ability (p = .006).
Active involvement in cognitively stimulating pursuits may be beneficial for persons with AD.
The Journals of Gerontology Series B Psychological Sciences and Social Sciences 03/2011; 66(4):416-25. · 2.62 Impact Factor
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Maria C Norton,
Ken R Smith,
Truls Østbye,
JoAnn T Tschanz, Chris Corcoran,
Sarah Schwartz,
Kathleen W Piercy,
Peter V Rabins,
David C Steffens,
Ingmar Skoog,
John C S Breitner,
Kathleen A Welsh-Bohmer
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ABSTRACT: To examine the effects of caring for a spouse with dementia on the caregiver's risk for incident dementia.
Population-based study of incident dementia in spouses of persons with dementia.
Rural county in northern Utah.
Two thousand four hundred forty-two subjects (1,221 married couples) aged 65 and older.
Incident dementia was diagnosed in 255 subjects, with onset defined as age when subject met Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria for dementia. Cox proportional hazards regression tested the effect of time-dependent exposure to dementia in one's spouse, adjusted for potential confounders.
A subject whose spouse experienced incident dementia onset had a six times greater risk for incident dementia as subjects whose spouses were dementia free (hazard rate ratio (HRR)=6.0, 95% confidence interval (CI)=2.2-16.2, P<.001). In sex-specific analyses, husbands had higher risks (HRR=11.9, 95% CI=1.7-85.5, P=.01) than wives (HRR=3.7, 95% CI=1.2-11.6, P=.03).
The chronic and often severe stress associated with dementia caregiving may exert substantial risk for the development of dementia in spouse caregivers. Additional (not mutually exclusive) explanations for findings are discussed.
Journal of the American Geriatrics Society 05/2010; 58(5):895-900. · 3.74 Impact Factor
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ABSTRACT: To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon4 genotype (APOE epsilon4) on cognitive decline.
Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE epsilon4, and cognitive trajectories.
Modified Mini-Mental State Examination score trajectories over time.
Compared with participants who did not have APOE epsilon4 or an FHxAD, those with APOE epsilon4 scored lower on the Modified Mini-Mental State Examination at baseline (-0.70 points; 95% confidence interval [CI], -1.15 to -0.24). Participants with an FHxAD and APOE epsilon4 differed less, if at all, in baseline score (-0.46 points; 95% CI, -1.09 to 0.16) but declined faster during the 7-year study (-9.75 points [95% CI, -10.82 to -8.67] vs -2.91 points [95% CI, -3.37 to -2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE epsilon4 declined much less during the 7-year study (-1.54; 95% CI, -2.59 to -0.50).
Much of the association among FHxAD, APOE epsilon4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive.
Archives of neurology 11/2009; 66(11):1378-83. · 6.31 Impact Factor
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P B Rosenberg,
M M Mielke,
J Tschanz,
L Cook, Chris Corcoran,
K M Hayden,
M Norton,
P V Rabins,
R C Green,
K A Welsh-Bohmer,
J C S Breitner,
R Munger,
C G Lyketsos
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ABSTRACT: Evidence suggests that cardiovascular medications, including statins and antihypertensive medications, may delay cognitive decline in patients with Alzheimer dementia (AD). We examined the association of cardiovascular medication use and rate of functional decline in a population-based cohort of individuals with incident AD.
In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors.
CDR-Sum increased an average of 1.69 points annually, indicating a steady decline in functioning. After adjustment for demographic variables and the baseline presence of cardiovascular conditions, use of statins (p = 0.03) and beta-blockers (p = 0.04) was associated with a slower annual rate of increase in CDR-Sum (slower rate of functional decline) of 0.75 and 0.68 points respectively, while diuretic use was associated with a faster rate of increase in CDR-Sum (p = 0.01; 0.96 points annually). Use of calcium-channel blockers, angiotensin-converting enzyme inhibitors, digoxin, or nitrates did not affect the rate of functional decline.
In this population-based study of individuals with incident AD, use of statins and beta-blockers was associated with delay of functional decline. Further studies are needed to confirm these results and to determine whether treatment with these medications may help delay AD progression.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 12/2008; 16(11):883-92. · 3.35 Impact Factor
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Katherine A Treiber,
Constantine G Lyketsos, Chris Corcoran,
Martin Steinberg,
Maria Norton,
Robert C Green,
Peter Rabins,
David M Stein,
Kathleen A Welsh-Bohmer,
John C S Breitner,
JoAnn T Tschanz
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ABSTRACT: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD).
The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status.
One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health.
Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.
International Psychogeriatrics 07/2008; 20(3):538-53. · 2.24 Impact Factor
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ABSTRACT: The purpose of this study is to examine number of live births, other reproductive factors, and health behaviors in relation to obesity risk among older women.
Data were collected during in-person and telephone-based interviews from a population-based cohort in Utah.
A total of 2,035 women aged 66-102 are included in this report. Overall, 403 (20%) older women were determined to be obese. The rates of obesity were significantly higher with increasing numbers of children, demonstrating a dose-response relationship (P < 0.05). After adjustment for age, education, marital status, BMI at age 18, use of oral contraceptives, hysterectomy status, physical activity, current use of hormone therapy, and age at menarche, the risk of obesity increased 11% with each additional live birth. In additional analyses that excluded nulliparous women, after adjusting for cumulative months of breast-feeding, the risk of obesity increased 7% with each live birth. In this cohort of older women, we found higher rates of obesity with increasing number of children that was independent of socioeconomic status and other confounding factors.
In a cohort of older women, higher rates of obesity were associated with increasing number of children that was independent of socioeconomic status and other confounding factors.
Preventive Medicine 01/2005; 40(1):99-104. · 3.22 Impact Factor
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ABSTRACT: To avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly.
We administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm's IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses.
A 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of < or =82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures.
The improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample.
Journal of Clinical Epidemiology 11/2003; 56(11):1038-45. · 4.27 Impact Factor
