Journal of Alzheimer's Disease - Volume 62, issue 2

Authors: Dorninger, Fabian | Moser, Ann B. | Kou, Jianqiu | Wiesinger, Christoph | Forss-Petter, Sonja | Gleiss, Andreas | Hinterberger, Margareta | Jungwirth, Susanne | Fischer, Peter | Berger, Johannes

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VITA) study, a longitudinal, population-based birth cohort study, at baseline and after 90 months or at diagnosis of probable AD. We determined the levels of specific choline phospholipids, …some of which have been suggested as potential biomarkers for the prediction of AD. Our results show that during normal aging the levels of lysophosphatidylcholine, choline plasmalogen, and lyso-platelet activating factor increase significantly. Notably, we observed similar but more pronounced changes in the group that developed probable AD. Thus, our results imply that, in terms of choline-containing plasma phospholipids, the conversion to AD mimics an accelerated aging process. We conclude that age, even in the comparatively short time frame between 75 and 82.5 years, is a crucial factor in the quest for plasma lipid biomarkers for AD that must be carefully considered in future studies and trials. Show more

Keywords: Biomarkers, blood, lyso-PAF, lysophosphatidylcholines, lysophospholipids, mass spectrometry, plasmalogens

DOI: 10.3233/JAD-171036

Citation: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 841-854, 2018

Authors: Wang, Dai | Schultz, Tim | Novak, Gerald P. | Baker, Susan | Bennett, David A. | Narayan, Vaibhav A.

Article Type: Research Article

Abstract: Background: Therapeutic research on Alzheimer’s disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. Objective: To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Methods: Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer’s Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic …activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Results: Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Conclusion: Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed. Show more

Keywords: Alzheimer’s disease, amyloid-β, basic activities of daily living, cognitive decline, functional decline, instrumental activities of daily living, neuropathology, preclinical

DOI: 10.3233/JAD-170903

Citation: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 855-865, 2018

Authors: Gilmartin-Thomas, Julia F.-M. | McNeil, John | Powell, Anne | Malone, Daniel T. | Wolfe, Rory | Larson, Ian C. | O’Reilly, Claire L. | Kirkpatrick, Carl M. | Kipen, Eva | Petrovich, Tanya | Bell, J. Simon

Article Type: Research Article

Abstract: Background: Clinical practice guidelines for dementia highlight the importance of providing patient-centered care. This can be achieved by improving health professionals’ attitudes and knowledge toward people with dementia. Objective: Quantitatively evaluate the impact of a virtual dementia experience on medical and pharmacy students’ knowledge and attitudes toward people with dementia. Methods: A non-randomized controlled study from September-October 2016. The intervention group received a 1.5-hour multisensory, virtual simulation of light, sound, color, and visual content to experience the cognitive and perceptual difficulties faced by people with dementia. Controls participated in the standard curriculum only. All students were …invited to complete the 20-item Dementia Attitudes Scale (DAS) pre- and post-intervention. Results: A total of 278 students (n  = 64 medical, n  = 214 pharmacy) were analyzed (n  = 80 intervention, n  = 198 control). The majority of students were female (n  = 184, 66.2%), with an average age of 22.5 years. The intervention improved the DAS total score and subdomains of comfort and knowledge (p  < 0.001). Conclusion: The intervention had a positive impact on medical and pharmacy students’ knowledge and attitudes toward people with dementia. Show more

Keywords: Alzheimer’s disease, dementia, education, medicine, pharmacy

DOI: 10.3233/JAD-170982

Citation: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 867-876, 2018

Authors: Tan, Bryce | Venketasubramanian, Narayanaswamy | Vrooman, Henri | Cheng, Ching-Yu | Wong, Tien Yin | Ikram, Mohammad Kamran | Chen, Christopher | Hilal, Saima

Article Type: Research Article

Abstract: Background: Plasma homocysteine levels are increasingly studied as a potential risk factor for dementia. Elevated homocysteine levels have been linked with gray and white matter volume reduction among individuals with mild cognitive impairment and Alzheimer’s disease. However, the effects of homocysteine on brain changes in preclinical stages of dementia remain unexplored. Objective: To examine the association of elevated homocysteine levels with markers of neurodegeneration, i.e., white and gray matter volume in an elderly population. Methods: The study included 768 participants (mean age: 69.6±6.5 years, 51.3% women) from the Epidemiology of Dementia In Singapore study. Participants underwent …a brain MRI scan and blood tests. Serum homocysteine was measured using competitive immunoassay. Cortical thickness and subcortical structural volume were quantified using FreeSurfer whereas white matter volume was quantified using a previous validated method. Results: Higher homocysteine levels were significantly associated with decreased global white matter volume [mean difference (β ) in volume (ml) per micromole per liter (μ mol/l) increase in homocysteine levels: – 0.555, 95% Confidence Interval (CI): – 0.873; – 0.237], decreased parietal cortical thickness [β in thickness (μ m) per μ mol/l increase in homocysteine levels:– 1.429, 95% CI: – 2.781; – 0.077], and smaller volumes of the thalamus [β : – 0.017, 95% CI: – 0.026; – 0.008], brainstem [β : – 0.037, 95% CI: – 0.058; – 0.016], and accumbens [β : – 0.004, 95% CI: – 0.006; – 0.002]. Conclusion: Higher homocysteine levels were associated with cerebral atrophy. Further studies are required to assess whether lowering plasma homocysteine levels may prevent neurodegenerative changes or delay progression of clinical symptoms before the development of dementia. Show more

Keywords: Cortical thinning, dementia, homocysteine, subcortical atrophy, white matter atrophy

DOI: 10.3233/JAD-170796

Citation: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 877-885, 2018