April 30, 2014

Alzheimer Disease & Associated Disorders January-March 2014

Full text articles are available to fee paying members of Alzheimer’s Australia NSW by emailing NSW.Library@alzheimers.org.au

Facilitating Alzheimer Disease Research Recruitment

Alzheimer disease (AD) research faces challenges to successful enrollment, especially to clinical trials and biomarker studies. Failure to recruit the planned number of participants in a timely manner threatens the internal validity and success of clinical research, raising concerns about external validity and generalizability of results, and possibly leading to disparities in disease treatment. Methods to improve recruitment exist, but require varying levels of staff effort and financial resources, and evidence of effectiveness is often lacking or inconsistent. In this review, we summarize some of the available methods to improve AD research recruitment, the available literature to support or refute these strategies, and some of the experiences at the authors’ AD Research Centers. We discuss the use of community-based participatory research principles and participant registries as a means to enhance research enrollment and increase diversity of research samples.
p. 1-8 

Vascular Risk Factors and Cognitive Decline in a Population Sample

We examined several vascular factors in relation to the rates of decline in 5 cognitive domains in a population-based cohort. In an age-stratified random sample (N=1982) aged 65+ years, we assessed at baseline the cognitive domains of attention, executive function, memory, language, and visuospatial function, and also vascular, inflammatory, and metabolic indices. Random effects models generated slopes of cognitive decline over the next 4 years; linear models identified vascular factors associated with these slopes, adjusting for demographics, baseline cognition, and potential interactions. Several vascular risk factors (history of stroke, diabetes, central obesity, C-reactive protein), although associated with lower baseline cognitive performance, did not predict rate of subsequent decline. APOE*4 genotype was associated with accelerated decline in language, memory, and executive functions. Homocysteine elevation was associated with faster decline in executive function. Hypertension (history or systolic blood pressure >140 mm Hg) was associated with slower decline in memory. Baseline alcohol consumption was associated with slower decline in attention, language, and memory. Different indices of vascular risk are associated with low performance and with rates of decline in different cognitive domains. Cardiovascular mechanisms explain at least some of the variance in cognitive decline. Selective survival may also play a role.
p. 9-15 

Midlife Cardiovascular Risk Impacts Executive Function: Framingham Offspring Study

Introduction: Novel error scores and traditional indices of executive function (EF) were related to cardiovascular risk factors measured 10 to 15 years earlier.
Methods: From 1991 to 1995, the Framingham Stroke Risk Profile (FSRP), a composite score of cardiovascular risk, was ascertained in 1755 Framingham Offspring participants (54% women, mean age=54±9 y). Participants were administered EF tests, which included: FAS and Animals Fluency tests, Trail Making Test B (TrB), and Digit Span-Backwards (DS-B), from 2005 to 2009. Linear and logistic regression were used to relate the FSRP and its components to both error responses and traditional scores.
Results: Consistent with previous findings, the FSRP and the individual components, diabetes and sex, were associated with several traditional measures of EF. Of interest were relationships between the FSRP score and TrB Total Errors (P=0.04), DS-B% Total Errors (P=0.02) and DS-B Capacity Score (P=0.03), and prevalent CVD related to making FAS Perseverations in the 75th percentile (P=0.03). By comparison, FSRP and CVD were not related to the traditional DS-B or FAS scores. In addition, age was associated with higher Animals % Total Errors and % Perseverations among ApoE4+ individuals and with higher TrB Total Errors among ApoE4− individuals.
Conclusions: For those middle-aged and healthy, including those who are ApoE4+, cardiovascular risk factors are related to impairments in EF as ascertained by novel errors and traditional measures.p. 16-22 

Incidence Rates of Dementia, Alzheimer Disease, and Vascular Dementia in the Japanese American Population in Seattle, WA: The Kame Project

There are few studies on the incidence of dementia in representative minority populations in the United States; however, no population-based study has been conducted on Japanese American women. We identified 3045 individuals aged 65+ with at least 1 parent of Japanese descent living in King County, WA in the period 1992 to 1994, of whom 1836 were dementia-free and were examined every 2 years (1994 to 2001) to identify incident cases of all dementias, Alzheimer disease (AD), vascular dementia (VaD), and other dementias.
p. 23-29 

Cerebral Subcortical Small Vessel Disease in Subjects With Pathologically Confirmed Alzheimer Disease: A Clinicopathologic Study in the Oxford Project to Investigate Memory and Ageing (OPTIMA)

The understanding of how cerebrovascular disease (CVD) contributes to dementia is hampered by a lack of agreed and validated pathologic methods to accord weight to the contribution of different aspects of CVD to dementia. A previous study from the Oxford Project to Investigate Memory and Ageing (OPTIMA) validated a scheme for assessing the contribution of subcortical small vessel disease (SVD) toward dementia in the elderly by showing a significant inverse relationship between the severity of SVD and cognition in subjects without any other dementia pathology using this method. In the present paper, the method has been used to assess severity of SVD in 161 cases of neuropathologically confirmed Alzheimer disease. The results showed there was no relationship between the SVD score and cognitive scores acquired in the last 2 years of life. SVD scores were significantly related to age (P<0.0017) and were slightly but significantly higher in females than males (P<0.049). SVD scores were not related to blood pressure at entry to OPTIMA and were significantly lower when compared with the cohort of OPTIMA cases with only CVD (mean 5.06±1.85 vs. 5.9±2.67; P<0.0065). We conclude that when Alzheimer disease pathology is present in elderly subjects, it overwhelms the modest contribution that SVD makes to cognitive impairment.
p. 30-35 

Body Mass Index, Weight Change, and Clinical Progression in Mild Cognitive Impairment and Alzheimer Disease

The speed and severity of clinical progression after Alzheimer disease (AD) diagnosis varies and depends on multiple factors, most not well elucidated. We assessed whether body mass index (BMI) and 1-year weight change (WC) are associated with clinical progression in amnestic mild cognitive impairment (aMCI) and early-stage AD. Longitudinal data comprising 2268 aMCI and 1506 AD participants in the National Alzheimer’s Coordinating Center’s Uniform Data Set were used to examine nuances of clinical progression by BMI and WC, as well as potential variations in associations by age, sex, BMI (WC model), or apolipoprotein E genotype. In aMCI, high BMI (vs. moderate BMI) was associated with slower progression; weight loss (vs. no WC) was associated with faster progression.
p. 36-43 

Pulse Wave Velocity and Cognitive Function in Older Adults

Arterial stiffness may be associated with cognitive function. In this study, pulse wave velocity (PWV) was measured from the carotid to femoral (CF-PWV) and from the carotid to radial (CR-PWV) with the Complior SP System. Cognitive function was measured by 6 tests of executive function, psychomotor speed, memory, and language fluency.
p. 44-49

Physical Activity and Cognitive Trajectories in Cognitively Normal Adults: The Adult Children Study

Increased physical activity may protect against cognitive decline, the primary symptom of Alzheimer disease. In this study, we examined the relationship between physical activity and trajectories of cognitive functioning over serial assessments. Cognitively normal (Clinical Dementia Rating 0) middle-aged and older adults (N=173; mean age, 60.7±7.8 y) completed a self-report measure of physical activity and a battery of standard neuropsychological tests assessing processing speed, attention, executive functioning, and verbal memory. At baseline, individuals with higher physical activity levels performed better on tests of episodic memory and visuospatial functioning. Over subsequent follow-up visits, higher physical activity was associated with small performance gains on executive functioning and working memory tasks in participants with one or more copies of the apolipoprotein ε4 allele (APOE4). In APOE4 noncarriers, slopes of cognitive performance over time were not related to baseline physical activity. Our results suggest that cognitively normal older adults who report higher levels of physical activity may have slightly better cognitive performance, but the potential cognitive benefits of higher levels of physical activity over time may be most evident in individuals at genetic risk for Alzheimer disease.
p. 50-57 

Factors Affecting Dementia Screening by General Practitioners in Community-dwelling Elderly Populations: A Large Cross-Sectional Study in 2 Areas of France

In patients aged 75 years and above, dementia is associated with increased expenditure and high morbimortality. Although the incidence of dementia is well known, it is often underrecognized in primary care. We conducted a cross-sectional study in 2 areas in the southeast of France to identify the factors affecting dementia-screening implementation by the French general practitioners (GPs). In May 2008, an anonymized survey was sent by e-mail and/or post to all GPs with a large clinic practice. Two months later, reminder letters were sent. Overall, 493 GPs answered (26.8%) to self-reported behavior. Of these, 73.2% felt that annual screening was useful, although only 24.5% implemented it each year and 17.5% implemented it every 2 to 5 years. Factors that favorably influenced screening practices were: the older age of the GPs; belief in the usefulness of annual dementia screening; increased frequency of follow-up visits by elderly patients; and the proportion of dementia in the GP’s practice. The main barrier to annual screening was the social problems encountered in the medical care of 75-year-old patients. Regardless of the differences in European national health policies or health care systems, all GPs encounter the same difficulties when dealing with elderly dementia patients.
p. 58-64 

Cortical and Subcortical Atrophy in Alzheimer Disease: Parallel Atrophy of Thalamus and Hippocampus

Brain atrophy is a key imaging hallmark of Alzheimer disease (AD). In this study, we carried out an integrative evaluation of AD-related atrophy. Twelve patients with AD and 13 healthy controls were enrolled. We conducted a cross-sectional analysis of total brain tissue volumes with SIENAX. Localized gray matter atrophy was identified with optimized voxel-wise morphometry (FSL-VBM), and subcortical atrophy was evaluated by active shape model implemented in FMRIB’s Integrated Registration Segmentation Toolkit. SIENAX analysis demonstrated total brain atrophy in AD patients; voxel-based morphometry analysis showed atrophy in the bilateral mediotemporal regions and in the posterior brain regions. In addition, regarding the diminished volumes of thalami and hippocampi in AD patients, subsequent vertex analysis of the segmented structures indicated shrinkage of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the volume of the thalami and hippocampi were highly correlated with the volume of the thalami and amygdalae on both sides in AD patients, but not in healthy controls. This complex structural information proved useful in the detailed interpretation of AD-related neurodegenerative process, as the multilevel approach showed both global and local atrophy on cortical and subcortical levels. Most importantly, our results raise the possibility that subcortical structure atrophy is not independent in AD patients.
p. 65-72 

Social Workers’ and Nurses’ Illness Representations About Alzheimer Disease: An Exploratory Study

Professionals’ perceptions of patients’ diseases (illness representations) are a major factor influencing the quality of treatment they provide. The aim of the study was to examine and compare Alzheimer disease (AD) illness representations among 2 main professional groups involved in the care of Alzheimer patients. A total of 327 nurses and social workers in Israel were asked to report their cognitive representations (dimensions of identity, cause, timeline, consequences, control, coherence, timeline cycle) and emotional representations. Knowledge about AD, demographic, and occupational characteristics were also obtained. Participants perceived AD as a chronic disease associated with severe consequences. Statistically significant differences were found between the groups, as nurses attributed psychological reasons to AD more than the social workers. Nevertheless, social workers perceived AD as more chronic with severe consequences compared with the nurses. Despite some resemblance, there were differences between the social workers and nurses regarding AD illness representations. Therefore, continuing to distribute materials to professionals regarding AD is recommended, with attention to the unique characteristics of each professional group. Furthermore, the findings encourage the development of training and support programs that will not only deal with the organizational and instrumental levels of treating AD patients but also with the assessment and consequences of professionals’ illness representations.
p. 73-78 

Effectiveness of a Psychoeducational Intervention Group Program in the Reduction of the Burden Experienced by Caregivers of Patients With Dementia: The EDUCA-II Randomized Trial

We conducted a multicenter, prospective, evaluator-blinded, 2-arm parallel randomized trial to compare the effectiveness of a group psychoeducational intervention (PIP) with that of standard care in dementia caregivers. The primary outcome was the burden experience evaluated by the Zarit Burden Interview. Secondary outcomes were psychological distress evaluated with the scaled General Health Questionnaire-28 items, and quality of life evaluated with the Short-Form Health Survey 12.

Retrospective and Prospective Data Collection Compared in the Dutch End of Life in Dementia (DEOLD) Study

Studying end of life in dementia patients is challenging because of ill-defined prognoses and frequent inability to self-report. We aim to quantify and compare (1) feasibility and (2) sampling issues between prospective and retrospective data collection specific to end-of-life research in long-term care settings. The observational Dutch End of Life in Dementia study (DEOLD; 2007 to 2011) used both prospective data collection (28 facilities; 17 nursing home organizations/physician teams; questionnaires between January 2007 and July 2010, survival until July 2011) and retrospective data collection (exclusively after death; 6 facilities; 2 teams, questionnaires between November 2007 and March 2010). Prospective collection extended from the time of admission to the time after death or conclusion of the study. p. 88-94 

Clomipramine in the Treatment of Compulsive Behavior in Frontotemporal Dementia: A Case Series

Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.
p. 95-98


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