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ABSTRACT: More than 1 million people in the United States have Parkinson disease (PD), more than are diagnosed as having multiple sclerosis, amyotrophic lateral sclerosis, muscular dystrophy, and myasthenia gravis combined. PD affects approximately 1 in 100 Americans older than 60 years. It burdens patients, their care partners, and the overall healthcare system. This article reviews the epidemiology, clinical features, putative environmental risk and protective factors, neuropathological aspects, heterogeneity, medical management, and recent studies regarding genetics and PD. The article suggests that based on new research, the prevalence of PD varies in different regions of the United States. Some progress has been made in identifying the risk and protective factors of PD, and a newly emphasized area of study in PD is genetics. Patient care recommendations, based on American Academy of Neurology practice guidelines, are outlined to show the state of contemporary medical management of PD and related disorders.
Southern medical journal 12/2012; 105(12):650-6. · 0.92 Impact Factor
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ABSTRACT: The John Henryism active coping (JHAC) hypothesis suggests that striving with life challenges predicts increased risk for cardiovascular disease for those with scarce coping resources. This study examined the moderating role of JHAC in the associations of 1) caregiver status and 2) care recipient functional status with diurnal salivary cortisol patterns among 30 African Americans (AAs) and 24 white female dementia caregivers and 63 noncaregivers (48 AAs).
Caregiver participants completed the JHAC-12 scale, Activities of Daily Living (ADL) scale, and Revised Memory and Behavior Problem checklist (RMBPC) and collected five saliva samples daily (at awakening, 9 A.M., 12 P.M., 5 P.M., and 9 P.M.) for 2 successive days.
Univariate analysis of variance tests with mean diurnal cortisol slope as the outcome illustrated that among AA caregivers, higher JHAC scores were related to flatter (or more dysregulated) cortisol slopes. The JHAC by ADL and JHAC by RMBPC interactions were each significant for AA caregivers. Among AA caregivers who reported higher ADL and RMBPC scores, higher JHAC scores were associated with flatter cortisol slopes.
These findings extend recent studies by showing that being AA, a caregiver, and high in JHAC may elevate the risk for chronic disease, especially for those with higher patient ADL and behavioral problems. Thus, it is imperative that interventions appreciate the pernicious role of high-effort coping style, especially for AA caregivers, to minimize the stressful side effects of patient ADL and memory and behavioral problems for the caregiver.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 05/2011; 19(5):451-60. · 3.35 Impact Factor
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ABSTRACT: To evaluate the safety of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in nondiabetic patients with Alzheimer disease (AD) and to explore treatment effect sizes on clinical outcomes.
Double-blind, placebo-controlled randomized controlled trial of 18-month duration.
Two academic medical center outpatient clinics.
Nondiabetic patients meeting research criteria for probable AD were enrolled. Twenty-five of 29 subjects completed the study; no withdrawals were attributable to adverse effects.
Subjects received pioglitazone (Actos), titrated to 45 mg daily, or matching placebo, and 200 IU of vitamin E daily. Patients maintained treatment with cholinesterase inhibitors and could begin memantine therapy when it became available during the study.
The primary outcome was frequency of reported adverse effects (AEs). Secondary outcomes were measures of cognition, activities of daily living, neuropsychiatric symptoms, and global function.
Peripheral edema was the principal AE occurring more frequently in subjects taking pioglitazone than placebo (28.6% vs 0%). This is consistent with the known AE profile of pioglitazone. No group differences in laboratory measures were identified. No significant treatment effect was observed on exploratory analysis of clinical efficacy.
Pioglitazone was generally well tolerated in this pilot study. There were no serious or unanticipated adverse events or clinical laboratory changes attributable to pioglitazone over a long-term exposure in nondiabetic patients with AD. The tolerability of pioglitazone in this population and peroxisome proliferator-activated receptor gamma effects in laboratory models of AD support further study of this drug class in earlier disease stages.
clinicaltrials.gov Identifier: NCT00982202.
Archives of neurology 01/2011; 68(1):45-50. · 6.31 Impact Factor
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ABSTRACT: In this chapter we describe a particular intervention, Early Memory Loss Clubs, that we believe exemplify the type of intervention
needed for those with Alzheimer’s disease and related disorders (ADRD). We summarize the current status of medical management
of ADRD and provide a brief introduction to non-pharmacological approaches to ADRD intervention and management.
12/2010: pages 381-400;
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ABSTRACT: Creative expression (CE) programs are emerging interventions to improve the quality of care and life of persons with dementia (PWDs) in long-term care settings. However, limited empirical evidence exists to support the effectiveness of these programs. Here, we report the findings from an assessment of the impact of TimeSlips (TS), a group storytelling program that encourages CE among PWDs and those who care for them.
Instruction in TS was provided through a 10-week on-site training. An observational study using an experimental design was conducted in 20 nursing home facilities in 2 states, 10 of which were randomly selected to implement TS. Two weeks after the implementation of TS at the intervention sites, we conducted 4 days of direct observation, using a time-sampling approach, of residents and staff in each facility. Using surveys, we also assessed staff job satisfaction, attitudes toward residents, and burnout.
Compared with residents in the control facilities, those in the TS facilities were more engaged and more alert. In TS facilities, there were more frequent staff-resident interactions, social interactions, and social engagement. Also, staff who participated in the TS program had more positive views of residents with dementia and devalued residents less than did the control group staff. There were no differences in staff job satisfaction and burnout among staff in the TS and non-TS facilities.
Implementing the TS program in nursing facilities improves the care environment for PWDs. However, additional studies are needed to offer further insights into the mechanisms by which TS improves both staff and resident outcomes.
The Gerontologist 03/2009; 49(1):117-27. · 2.48 Impact Factor
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Thomas Fritsch
Southern medical journal 07/2008; 101(7):677-8. · 0.92 Impact Factor
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ABSTRACT: The purpose of this study was to examine the role of adolescent IQ (AIQ) and gender in older adults' ability to use cognitive support to enhance memory. Subjects were 269 mid-1940s graduates of the same high school. Adolescent IQ scores were gathered from archives, and subjects' memory for words was tested with tasks that provided increasing cognitive support. Overall, subjects benefited from support; women recalled more words than men; and persons with a high AIQ remembered more words than persons with a lower AIQ. However, while all subjects showed gains from cognitive support, men with a lower AIQ performed worse than men with a high AIQ. Women's performance was not dependent on their AIQ. Analysis of qualitative memory indicators suggested that women and persons with a high AIQ had better encoding and retrieval operations. Men with a lower AIQ appear to be particularly vulnerable to memory deficits in aging. This may be due to low "cognitive reserve" or generally poorer episodic memory function.
Aging Neuropsychology and Cognition 08/2007; 14(4):394-416. · 1.07 Impact Factor
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ABSTRACT: The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender-specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results.
Journal of Alzheimer's disease: JAD 07/2007; 11(3):313-21. · 3.74 Impact Factor
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ABSTRACT: According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues.
349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables.
Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education. Verbal fluency, in contrast, was affected by adolescent IQ through links with high school mental activities, but not education.
Our study suggests that reserve is dynamic, but it is most amenable to change in early life. We conclude that an active, engaged lifestyle, emphasizing mental activity and educational pursuits in early life, can have a positive impact on cognitive functioning in late life.
The Gerontologist 07/2007; 47(3):307-22. · 2.48 Impact Factor
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ABSTRACT: The purpose of this study is to examine the relationship of height, Apolipoprotein E genotype (APOE) and Alzheimer's disease (AD). Using a case-control design, subjects were recruited from the research registry of the University Memory and Aging Center of Case Western Reserve University and University Hospitals of Cleveland. On entry to the study, height was measured on 239 probable or possible AD patients and 341 healthy controls living in northeast Ohio. Risk of AD was modeled as a function of quartile of height, APOE genotype, years of education and year of birth. Analyses were stratified by gender. For men, cases were more likely to be shorter when compared to controls (p=0.001). There was only a small difference in mean height between AD cases and controls among women (p=0.05). For men, height in the highest quartile [>179.7 cm (70.75 in)] had a 59% lower risk of developing AD that in the lowest quartile [< 169.5 cm (66.75 in)], controlling for year of birth, and education (p=0.03). For women without an APOE epsilon4 allele, increasing height was associated with lower risk for AD (OR=0.88; p=0.01) but no significant association was found for women with at least one epsilon4 allele (OR=1.03; p=0.56).
Journal of Alzheimer's disease: JAD 06/2007; 11(3):337-41. · 3.74 Impact Factor
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ABSTRACT: Using a sociocultural stress and coping model, this pilot study examines the influence of depressive symptoms and stress on diurnal salivary cortisol patterns among African American (N=30) and European American (N=24) female dementia caregivers and noncaregivers (African American, N=48; European American, N=15). Caregiving participants completed the Center for Epidemiological Studies Depression Scale (CES-D), Perceived Stress Scale (PSS), and Stress-Related Growth Scale (SRGS) as respective measures of depressive symptoms, stress, and stress resilience. Participants also collected five saliva samples daily for two consecutive days. African American caregivers scored significantly higher than European American caregivers on the SRGS, but they did not differ on the PSS and CES-D scales. Regression analyses with age, ethnicity, caregiving status, and depressive symptoms as predictors, and cortisol slope as criterion, showed that only age and ethnicity predicted cortisol slope. African Americans had flatter slopes than the European Americans sampled, regardless of caregiving status. Findings highlight the role of cultural beliefs and of ethnicity in explaining cortisol function.
American Journal of Geriatric Psychiatry 09/2006; 14(8):684-93. · 3.64 Impact Factor
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ABSTRACT: The objective was to study the associations between participation in different types of mentally stimulating leisure activities and status as Alzheimer's disease (AD) case or normal control. Research suggests that participation in leisure activities, especially mentally stimulating activities, is associated with a lower risk for AD. However, no study has yet evaluated associations between AD and different types of mental leisure activities, especially those involving "novelty seeking." The authors used a case-control design to compare participation in activities across the life span in persons with AD and normal controls. Cases (n = 264) were recruited from clinical settings and from the community. Controls were drawn from 2 populations. Control group A members (n = 364) were the friends or neighbors of the cases or members of the same organizations to which the cases belonged. Control group B members (n = 181) were randomly drawn from the community. The 2 control groups did not differ in their responses to most activity questions, so they were combined. Factor analysis of activity questions identified 3 activity factors: (1) novelty seeking; (2) exchange of ideas; and (3) social. Logistic regression analysis indicated that, adjusting for control variables, greater participation in novelty-seeking and exchange-of-ideas activities was significantly associated with decreased odds of AD. The odds of AD were lower among those who more often participated in activities involving exchange of ideas and were lower yet for those who more frequently participated in novelty-seeking activities. We conclude that participation in a variety of mental activities across the life span may lower one's chances of developing AD.
Journal of Geriatric Psychiatry and Neurology 10/2005; 18(3):134-41. · 3.07 Impact Factor
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ABSTRACT: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth.
Retrospective cohort study.
Research volunteers living throughout the United States.
A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s.
Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education.
High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95% CI=0.12-0.84). No association was found between sex or education and adult cognitive status in this model.
High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological "reserve," and involvement in activities may contribute to "reserve." Early neuropathology and ascertainment bias are also possible explanations for the observed associations.
Journal of the American Geriatrics Society 08/2005; 53(7):1191-6. · 3.74 Impact Factor
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ABSTRACT: The relationship between leisure activities and development of cognitive impairment in aging has been the subject of recent research. We examined television viewing in association with risk of developing Alzheimer's disease (AD) in a case-control study. Given recent focus on the importance of intellectually stimulating activities as preventive measures against cognitive decline, it is important to examine the effects of less stimulating but common activities. Data are from 135 Alzheimer's disease cases and 331 healthy controls. Demographic characteristics and life history questionnaire responses on the number of hours spent on 26 leisure activities during middle-adulthood (ages 40-59) were analyzed. Logistic regression was used to examine the effects of middle-adulthood leisure activities on case vs. control status. Results indicate that for each additional daily hour of middle-adulthood television viewing the associated risk of AD development, controlling for year of birth, gender, income, and education, increased 1.3 times. Participation in intellectually stimulating activities and social activities reduced the associated risk of developing AD. Findings are consistent with the view that participation in non-intellectually stimulating activities is associated with increased risk of developing AD, and suggest television viewing may be a marker of reduced participation in intellectually stimulating activities.
Brain and Cognition 08/2005; 58(2):157-65. · 3.17 Impact Factor
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ABSTRACT: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was developed to evaluate cognitive impairments associated with Alzheimer's disease (AD). Previous studies have suggested that the battery is multi-dimensional, represented by either 3 or 5 dimensions. In this study a principal factor analysis was conducted using contemporary quantitative methods for determining the number of factors. Exploratory factor analysis of the CERAD battery and MMSE was conducted using one-half of the CERAD database (total N = 969). Glorfeld's modification of Horn's parallel analysis method suggested that there was 1 common factor in the variable matrix. Characterization of patterns of deficits in AD requires supplementation of measures derived from the CERAD and MMSE with other tests.
Journal of the International Neuropsychological Society 08/2004; 10(4):559-65. · 2.76 Impact Factor
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ABSTRACT: Studies of caregivers illustrate a classic sampling dilemma: maximizing recruitment without compromising study validity. Because caregivers are defined in relation to a care recipient, sampling methods are often determined by pragmatic decisions such as access, efficiency, and costs. However, overlooking validity may result in selection bias, misclassification of caregiver status, and the confounding of results. Validity and pragmatic concerns were compared in four caregiver studies that used different sampling frames: community based, Alzheimer's disease registry, and ancillary studies to existing epidemiologic studies.
Systematic comparison of validity and of pragmatic aspects of sampling frames, recruitment methods, and participation rates, with attention to caregiver identification, inclusion criteria, and sample restriction.
All studies used task-based inclusion criteria. Caregiver participation rates ranged from 81% to 96%, with higher rates in community-based and registry-based studies than in ancillary studies. The latter studies benefited from unbiased selection of noncaregivers.
Regardless of sampling frame, standard task-based inclusion criteria to define caregivers may enhance validity.
Journal of Aging and Health 02/2004; 16(2):175-203. · 1.56 Impact Factor
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ABSTRACT: To develop a scale that can assist in predicting likelihood of decline from mild dementia over 1 year in patients with Alzheimer's disease (AD).
Retrospective cohort study.
University Memory and Aging Center.
Patients with probable or possible AD and Clinical Dementia Rating (CDR) of 1 at baseline, divided into development and validation cohorts (n = 118 each).
The CDR and neurological and neuropsychological assessments were given at baseline and 1 year later.
In the development cohort, high education, low Mini-Mental State Examination score, poor insight, psychotic symptoms, and greater activity of daily living impairment predicted decline in CDR from 1 to 2 or 3. Receiver operating characteristics (ROC) curve analysis identified cutoff scores that maximized sensitivity and specificity for each significant predictor of decline. Based on the cutoff, raw scores were recoded to reflect risk for decline, weighted, and summed to create a final scale score. ROC curve analysis established a cutoff to indicate risk for decline on the final scale score. Sensitivity, specificity, and area under the ROC were 0.76, 0.74, and 0.83 in the development cohort and 0.77, 0.69, and 0.80 in the validation cohort, respectively. Positive and negative predictive values were 0.71 and 0.78 in the development cohort and 0.68 and 0.78 in the validation cohort, respectively.
Decline from mild to moderate or severe impairment represents significant clinical change, with implications for patient and caregiver quality of life and treatment options. The clinical scale developed uses data to enhance prediction about change from mild to moderate or severe stages of AD.
Journal of the American Geriatrics Society 02/2003; 51(1):91-5. · 3.74 Impact Factor
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ABSTRACT: Researchers have suggested that educational attainment and occupational status--indicators of cognitive and/or neurologic "reserve"--can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be "direct" independent of occupational status), "indirect" (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subjects included persons with "probable" or "possible" AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethnicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a "direct" effect of education on decline in MMSE, but no "indirect" effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus, the protective effects of reserve may be established early in life, before people enter the workforce.
International Psychogeriatrics 01/2003; 14(4):347-63. · 2.24 Impact Factor
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ABSTRACT: The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of “diversity” (total number of activities), “intensity” (hours per month), and “percentage intensity” (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65–5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20–39) to middle adulthood (40–60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.
Proceedings of the National Academy of Sciences 03/2001; · 9.68 Impact Factor
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ABSTRACT: Recruitment and retention of African Americans into Alzheimer disease (AD) research studies poses challenges owing to long-standing socio-economic and cultural differences, pragmatic difficulties in reaching the African American population, and a legacy of distrust of medical research. In this study, we report on our efforts to use live theater to educate African Americans about AD research and to increase minority participation in it. We describe our experiences at the University Memory and Aging Center (Cleveland, OH) in commissioning, writing, and producing several theater productions focused on themes related to African Americans and their experiences dealing with family members with AD. Analysis of recruitment data, gathered before and after one of our productions, indicated that minority enrollment into our Center's Research Registry increased after the play. Survey data, gathered before and after production of a different play, indicated that viewing this piece increased knowledge about: (1) the symptoms of AD; (2) the fact that memory loss is not a part of normal aging; and (3) the greater prevalence of AD among African Americans. Also, after viewing this production, more audience members: (1) reported knowing how to become involved in research; (2) felt comfortable involving family members in research; and (3) would recommend research to others. We conclude that live theater that dramatizes the experiences of a family living with a person with AD can increase knowledge about AD, improve attitudes about taking part in research, and lead to greater participation in AD research studies. An explanatory model is offered to account for our findings.
Alzheimer Disease and Associated Disorders 20(2):105-11. · 2.81 Impact Factor
