Journal of Alzheimer's Disease - Volume 49, issue 3

Authors: Shan, Ye | Wang, Dan-Dan | Xu, Yu-Xia | Wang, Chu | Cao, Lan | Liu, Yun-Sheng | Zhu, Cui-Qing

Article Type: Research Article

Abstract: Stress is an important risk factor of Alzheimer’s disease (AD). It has been evidenced that stress could induce tau phosphorylation and increase tau insolubility in brain; however, little is known about the interactional effect of stress with aging on tauopathy. Therefore, we explored the effects of aging on stress-induced tauopathy and the potential mechanism in mouse model of chronic restraint stress (CRS). Here we found that in general, the level of phosphorylated tau (P-tau) was higher in brain of middle-aged mice than that in adult mice under physiological conditions. CRS-induced tau phosphorylation and its insolubility were more prominent in middle-aged …mice. The increase of AT8-labeled insoluble P-tau was dramatic in middle-aged mice, which was highly ubiquitinated but did not form PHF structures. The levels of chaperones were relatively lower in middle-aged mice brain; CRS further reduced the expression, especially for HDJ2/HSP40. CRS also suppressed the expression of Pin1, the peptidylprolyl cis/trans isomerase, in middle-aged mice but not in adult mice. Downregulation of HSP40 or Pin1 caused an increase of transfected extraneous tau in 293 cells. Rosmarinic acid (RA) could effectively suppress the elevation of P-tau and insoluble P-tau formation induced by CRS, and reversed the abnormal changes of chaperones and Pin1 particularly in middle-aged mice. Taken together, our findings provided evidence that aging could be a promoting factor in stress-induced tauopathy, which was relevant with malregulation of chaperones and Pin1, and RA might be a promising beneficial agent for stress-induced tauopathy. Show more

Keywords: Aging, chronic restraint stress, chaperones, insolubility, rosmarinic acid, tau phosphorylation

DOI: 10.3233/JAD-150486

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 829-844, 2016

Authors: Han, S. Duke | Boyle, Patricia A. | James, Bryan D. | Yu, Lei | Bennett, David A.

Article Type: Research Article

Abstract: Background: Falling victim to financial scams can have a significant impact upon social and financial wellbeing and independence. A large proportion of scam victims are older adults, but whether older victims with mild cognitive impairment (MCI) are at higher risk remains unknown. Objective: We tested the hypothesis that older persons with MCI exhibit greater susceptibility to scams compared to those without cognitive impairment. Methods: Seven hundred and thirty older adults without dementia were recruited from the Rush Memory and Aging Project, a community-based epidemiologic study of aging. Participants completed a five-item self-report measure of susceptibility to …scams, a battery of cognitive measures, and clinical diagnostic evaluations. Results: In models adjusted for age, education, and gender, the presence of MCI was associated with greater susceptibility to scams (B  = 0.125, SE = 0.063, p -value = 0.047). Further, in analyses of the role of specific cognitive systems in susceptibility to scams among persons with MCI (n  = 144), the level of performance in two systems, episodic memory and perceptual speed abilities, were associated with susceptibility. Conclusions: Adults with MCI may be more susceptible to scams in old age than older persons with normal cognition. Lower abilities in specific cognitive systems, particularly perceptual speed and episodic memory, may contribute to greater susceptibility to scams in those with MCI. Show more

Keywords: Cognition, episodic memory, mild cognitive impairment, processing speed, scam

DOI: 10.3233/JAD-150442

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 845-851, 2016

Authors: Tu, Sicong | Leyton, Cristian E. | Hodges, John R. | Piguet, Olivier | Hornberger, Michael

Article Type: Research Article

Abstract: Background: Clinico-pathological distinction of primary progressive aphasia (PPA) can be challenging at clinic presentation. In particular, cross-sectional neuroimaging signatures across the logopenic (lvPPA) and semantic (svPPA) variants are difficult to establish, with longitudinal profiles showing greater divergence. Objective: Assess longitudinal propagation of white matter degradation in lvPPA and svPPA to determine disease progression over time, and whether this reflects distinct underlying pathology. Method: A cohort of 27 patients with dementia (12 lvPPA; 15 svPPA) and 12 healthy controls were assessed at baseline and 1-year follow-up on the Addenbrooke’s Cognitive Examination-Revised and Sydney Language Battery. Diffusion weighted …images were collected at both time-points and analyzed for longitudinal white matter change using DTI-TK and TBSS. Results: LvPPA patients showed a significant decline in naming and repetition, over 1 year, while svPPA patients declined in naming and comprehension. Longitudinal imaging revealed widespread bilateral degradation of white matter tracts in lvPPA over a 1-year period with early involvement of the left posterior inferior longitudinal fasciculus (ILF). SvPPA demonstrated focal left lateralized white matter degradation involving the uncinate fasciculus (UF) and anterior ILF, propagating to the right UF with disease progression. Conclusions: LvPPA and svPPA cohorts showed distinct longitudinal cognitive and white matter profiles. We propose differences in multi-centric and focal white matter dysfunction in lvPPA and svPPA, respectively, reflect underlying pathological differences. The clinical relevance of white matter degradation and mechanisms underlying disease propagation are discussed. Show more

Keywords: Diffusion tensor imaging, frontotemporal dementia, primary progressive aphasia, white matter

DOI: 10.3233/JAD-150626

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 853-861, 2016

Authors: van Uden, Ingeborg W.M. | van der Holst, Helena M. | Tuladhar, Anil M. | van Norden, Anouk G.W. | de Laat, Karlijn F. | Rutten-Jacobs, Loes C.A. | Norris, David G. | Claassen, Jurgen A.H.R. | van Dijk, Ewoud J. | Kessels, Roy P.C. | de Leeuw, Frank-Erik

Article Type: Research Article

Abstract: Background: The relationship between cerebral small vessel disease (SVD) and dementia has been studied without considering white matter (WM) volume, the microstructural integrity of the WM surrounding the SVD, and grey matter (GM). Objective: We prospectively investigated the relationship between these structures and the risk of dementia, and formed a prediction model to investigate which characteristics (macro- or microstructural) explained most of the variance. Methods: The RUN DMC study is a prospective cohort study among 503 non-demented participants with an age between 50 and 85 years at baseline, with baseline assessment in 2006 and follow-up assessment …in 2012. Two were lost to follow-up (yielding a 99.6% response-rate). Cox regression analysis was used, to calculate hazard ratios for dementia, of baseline MRI characteristics. Tract-Based Spatial Statistics (TBSS) analysis was used to assess the added value of microstructural integrity of the WM. Results: Mean age at baseline was 65.6 years (SD 8.8) and 56.8% was male. 43 participants developed dementia (8.6% ), resulting in a 5.5-year cumulative risk of 11.1% (95% CI 7.7–14.6). Low WM and hippocampal volume are significant predictors for dementia. WM, WM hyperintensities, and hippocampal volume explained most of the variance. TBSS analyses showed no additional value of diffusion parameters. Conclusions: WM and hippocampal volume were the main predictors for the development of incident dementia at 5-year follow-up in elderly with SVD. There was no additional diagnostic value of the diffusion tensor imaging parameters on top of the macrostructural characteristics. Show more

Keywords: Dementia, diffusion tensor imaging, elderly, hippocampal volume, small vessel disease, Magnetic resonance imaging, white matter

DOI: 10.3233/JAD-150573

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 863-873, 2016

Authors: Hsieh, Sharpley | Leyton, Cristian E. | Caga, Jashelle | Flanagan, Emma | Kaizik, Cassandra | O’Connor, Claire M. | Kiernan, Matthew C. | Hodges, John R. | Piguet, Olivier | Mioshi, Eneida

Article Type: Research Article

Abstract: Background and aims: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent a disease spectrum. Caregiver burden in subtypes of FTD has not yet been directly compared with those patients who have co-existent FTD and ALS (ALSFTD). Method: Perceived caregiver burden was evaluated using the short Zarit Burden Interview (ZBI) in patients with behavioral-variant FTD (bvFTD, n  = 21), semantic dementia (SD, n  = 18), and ALSFTD (n  = 15) at the initial clinical presentation and follow-up assessments. The Mini-Addenbrooke’s Cognitive Examination (M-ACE) and the Motor Neuron Disease Behaviour Scale (MiND-B) were also used. Linear mixed effects models examined longitudinal changes …on the ZBI, M-ACE, and MiND-B across groups. Results: Burden at baseline was highest for the bvFTD group. Longitudinally, perceived burden increased for the SD and ALSFTD groups whereas in bvFTD, the level of burden which was high at baseline and remained high with disease progression. The severity of abnormal behaviors at baseline, as assessed by the MiND-B, correlated with baseline levels of caregiver burden and further accounted for 23% of the variance in caregiver burden at clinical follow-up. Conclusions: The trajectory of perceived burden differs across the FTD-ALS spectrum, with SD and ALSFTD caregivers demonstrating an increased burden that develops over time, compared to a persistently high level for bvFTD caregivers, evident throughout the disease course. The evolution of burden in these three syndromes likely reflects the initial presentation and clinical characterization that develops with time. Psycho-education programs for caregivers, which provide better coping strategies for challenging behaviors, may reduce levels of burden experienced with disease progression. Show more

Keywords: Amyotrophic lateral sclerosis, burden of illness, caregivers, frontotemporal dementia, longitudinal studies, neuropsychiatry, semantic dementia

DOI: 10.3233/JAD-150475

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 875-885, 2016

Authors: Lewczuk, Piotr | Kornhuber, Johannes | Toledo, Jon B. | Trojanowski, John Q. | Knapik-Czajka, Malgorzata | Peters, Oliver | Wiltfang, Jens | Shaw, Leslie M.

Article Type: Correction

DOI: 10.3233/JAD-159006

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 887-887, 2016

Article Type: Other

DOI: 10.3233/JAD-150894

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 889-892, 2016