Alzheimer's and Dementia: Translational Research and Clinical Interventions
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User experience and clinical effectiveness with two wearable global positioning system devices in home dementia careAbstract Introduction The user experience and clinical effectiveness with wearable global positioning system (GPS) devices for persons with dementia (PwDs) and caregivers (CGs) remain unclear although many are available. Methods Using a crossover design, 20 dyads tested two similar commercial GPS watches (products A and B) at home for 4 weeks each. Usability, product functions, design features and product satisfaction at home and the clinic were investigated. Caregiver burden and quality of life assessed clinical effectiveness. Results The final 17 dyads rated the usability, telephone function, overall design features, font, buttons, and battery life of B significantly better than A. PwDs rated the overall design features and buttons of A significantly better than CGs. Product satisfaction with both products was significantly lower at home. Clinical effectiveness was not found. Discussion User experience can be improved by optimizing specific product details. This might translate to clinical effectiveness. Social desirability bias may explain different product satisfaction ratings.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 4 - Trang 636-644 - 2018
A general neurologist's perspective on the urgent need to apply resilience thinking to the prevention and treatment of Alzheimer's diseaseAbstract The goal of this article was to look at the problem of Alzheimer's disease (AD) through the lens of a socioecological resilience‐thinking framework to help expand our view of the prevention and treatment of AD. This serious and complex public health problem requires a holistic systems approach. We present the view that resilience thinking, a theoretical framework that offers multidisciplinary approaches in ecology and natural resource management to solve environmental problems, can be applied to the prevention and treatment of AD. Resilience thinking explains a natural process that occurs in all complex systems in response to stressful challenges. The brain is a complex system, much like an ecosystem, and AD is a disturbance (allostatic overload) within the ecosystem of the brain. Resilience thinking gives us guidance, direction, and ideas about how to comprehensively prevent and treat AD and tackle the AD epidemic.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 3 - Trang 498-506 - 2017
Neural and behavioral substrates of disorientation in mild cognitive impairment and Alzheimer's diseaseAbstract Background The neural and cognitive substrates of measures of orientation as used in clinical trials and examinations have not been comprehensively examined. Methods We studied 473 subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) at baseline in Alzheimer's Disease Neuroimaging Initiative. Regression analyses at baseline were conducted to find significant predictors of orientation score among cognitive, brain morphometry, and glucose metabolism measures. Mixed model longitudinal analysis was performed to examine consequences of orientation on functional decline, and Cox hazard models examined the risk of conversion to AD in the MCI group. Results In MCI and AD subjects, orientation was predicted by poorer neurocognitive performance on immediate and delayed episodic memory and attention and processing speed. Among magnetic resonance imaging measures, orientation was predicted by entorhinal cortex thickness, hippocampal volume, and inferior temporal cortex thickness. Glucose metabolism in both middle‐inferior temporal cortex and hippocampus were also predictive of orientation score. Functioning was significantly lower in disoriented subjects after 4 years of follow‐up, and MCI patients who also were disoriented showed a higher rate of conversion to AD with a hazard ratio of 1.5. Conclusions Orientation is associated with medial temporal lobe structure, temporal lobe glucose metabolism, and episodic memory function. In MCI individuals orientation was a risk factor for progression to AD, also associated with rapid functional decline and worse prognosis. Thus, orientation may serve as a surrogate for episodic memory in clinical examination. These results have direct implications for the use of orientation in MCI and AD clinical trials including ceiling effects in healthy controls and issues of redundancy with measures of memory, when both are used in composite scores.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 1 - Trang 37-45 - 2015
A model of lipid dysregulation and altered nutrient status in Alzheimer's diseaseAbstract Introduction Dysregulated lipid metabolism and nutrient status are thought to play a role in the pathophysiology of Alzheimer's disease (AD). However, the precise involvement is not well understood, and it remains unclear exactly how such dysregulated lipid metabolism and altered nutrient status, especially changes in phosphatidylcholine, B12, and folate, are connected to the hallmark pathology in AD (i.e., amyloidogenesis). Methods We have postulated that genetic susceptibility (i.e., APOE ε4/ε4) to environmental exposure to emissions of nitrous oxide (N2 O) could underlie the onset of AD and its early neuropsychiatric correlates Results and Discussion The current theoretical editorial describes, using clinical, preclinical, and in vitro evidences, how this model contributes not only to amyloidogenesis but also other nonopioid effects, specifically altered lipid metabolism, depletion of vitamin B12, and disruption of the folate‐mediated one carbon metabolic pathway.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 5 - Trang 139-145 - 2019
Amyloid‐associated increases in longitudinal report of subjective cognitive complaintsAbstract Introduction To investigate whether baseline subjective cognitive complaints (SCCs) predict longitudinal decline on neuropsychological testing and whether SCC increases longitudinally, in the setting of high levels of amyloid burden. Methods Two hundred seventy‐nine clinically normal older participants (mean age = 73.7 ± 6.1 years) from the Harvard Aging Brain Study, a cohort of community‐dwelling individuals, were followed longitudinally (4.27 ± 1.35 years) with annual subjective memory questionnaires and neuropsychological assessment. 11 C Pittsburgh compound‐B positron emission tomography was used to measure cortical amyloid and to classify status (Aβ+/Aβ−) at baseline. Results Higher baseline SCC predicted more rapid cognitive decline on neuropsychological measures among those with elevated amyloid (t = −2.18, P < .0001). In addition, longitudinal report of SCC significantly increased over time, with SCC progression most pronounced among Aβ+ individuals (t = 2.24, P = .0005). Discussion SCC may inform risk for future cognitive decline and track progression of self‐perceived decline, particularly in those along the AD trajectory, providing potentially important indicators of clinical meaningfulness in AD prevention trials.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 4 - Trang 444-449 - 2018
Promising results from a pilot study to reduce distress in Vietnamese American dementia and memory loss caregiversAbstract Introduction This study developed and examined the feasibility of a culturally tailored, evidence‐based skill‐building program to reduce stress and depression of Vietnamese American dementia caregivers. Methods This pilot randomized controlled trial included pretest and posttest measures using the Center for Epidemiologic Studies‐Depression Scale and the Revised Memory and Behavior Problems Checklist. The intervention (n = 30) group participated in a culturally tailored, 4‐week Vietnamese‐language cognitive‐behavioral skills evidenced‐based program (Our Family Journey); caregivers in the control condition (n = 30) received dementia‐related educational materials (education control condition). Results Our Family Journey caregivers showed significantly lower somatic scores on the Center for Epidemiologic Studies‐Depression Scale and reported lower frequency of care recipients' disruptive behaviors. However, they also reported being more stressed by their care recipients' depressive symptoms on the Revised Memory and Behavior Problems Checklist compared to caregivers in the education control condition. Discussion These promising results suggest that a culturally adapted program can benefit Vietnamese dementia caregivers. Additional research is needed to develop and evaluate stronger, more impactful interventions for this underserved group.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 5 - Trang 319-327 - 2019
Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary reportAbstract Introduction Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Methods Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural magnetic resonance imaging, and amyloid positron emission tomography (PET) scans. Results We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Discussion Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow‐up, and tau‐PET scans will provide more information in the future.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 3 - Trang 177-188 - 2017
Pharmaceutical company payments to the authors of the Japanese dementia clinical practice guidelines in 2016Abstract Introduction Financial relationships between pharmaceutical companies and dementia clinical practice guideline (CPG) authors are possibly biasing the recommendations in Japan. This study aimed to reveal characteristics and distribution of pharmaceutical payments made to Japanese dementia CPG authors and an extent of the transparency in the conflicts of interest disclosure among them. Methods We retrospectively retrieved the publicly available data on payment to all the authors in the dementia CPGs by major pharmaceutical companies in Japan in 2016. Results The total and mean payment values from pharmaceutical companies were $880,061 and $14,427, respectively. Of the 61 authors, 49 (80.3%) physicians received at least one payment. Financial relationships of the individual authors were not disclosed in the CPGs. Discussion Pharmaceutical companies with antidementia drugs had strong financial relationships with the CPG authors. To guarantee fairness in their relationships, it is imperative to establish a framework to disclose the corporate financial conflicts of interest.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 5 - Trang 228-230 - 2019
The ALFA project: A research platform to identify early pathophysiological features of Alzheimer's diseaseAbstract Introduction The preclinical phase of Alzheimer's disease (AD) is optimal for identifying early pathophysiological events and developing prevention programs, which are shared aims of the ALFA project, including the ALFA registry and parent cohort and the nested ALFA+ cohort study. Methods The ALFA parent cohort baseline visit included full cognitive evaluation, lifestyle habits questionnaires, DNA extraction, and MRI. The nested ALFA+ study adds wet and imaging biomarkers for deeper phenotyping. Results A total of 2743 participants aged 45 to 74 years were included in the ALFA parent cohort. We show that this cohort, mostly composed of cognitively normal offspring of AD patients, is enriched for AD genetic risk factors. Discussion The ALFA project represents a valuable infrastructure that will leverage with different studies and trials to prevent AD. The longitudinal ALFA+ cohort will serve to untangle the natural history of the disease and to model the preclinical stages to develop successful trials.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 2 - Trang 82-92 - 2016
A dopamine receptor genetic variant enhances perceptual speed in cognitive healthy subjectsAbstract Introduction Cognition is under strong genetic control, yet the specific genes are unknown. Methods One hundred and fifty‐three cognitive healthy European subjects from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning). Results One hundred and fifty‐nine variants nominally were found significant in the RANN cohort and re‐evaluated in an independent cohort of 868 cognitive healthy subjects from the Religious Orders Study and Rush Memory Aging Project. Meta‐analysis yielded a Bonferroni adjusted statistically significant association between perceptual speed and a variant located in the promoter of the dopamine receptor D4 gene, rs3756450 (β = 0.23, standard error = 0.05, P meta −5 ). Discussion Our data suggest that genetic variation in a dopamine pathway gene influences perceptual speed performance in cognitively healthy individuals.
Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 3 - Trang 254-261 - 2017
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