Journal of Alzheimer's Disease - Volume 57, issue 3

Authors: Wei, Meng | Zhao, Beiyu | Huo, Kang | Deng, Yongning | Shang, Suhang | Liu, Jie | Li, Yanbo | Ma, Louyan | Jiang, Yu | Dang, Liangjun | Chen, Chen | Wei, Shan | Zhang, Juanli | Yang, Hailei | Gao, Fan | Qu, Qiumin

Article Type: Research Article

Abstract: Background: Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer’s disease (AD). Objective: The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. Methods: A clinical trial was conducted between March 1, 2016, and April 1, 2016. Twenty volunteers (age 27.3±3.4 years) with normal cognitive function and sleeping habits were recruited from the local population. Participants underwent 24 h of TSD. Periprocedural blood samples were …collected to compare the changes of plasma Aβ42 , Aβ40 , low-density lipoprotein receptor-related protein (sLRP-1), soluble receptors for advanced glycation end products (sRAGE), and serum superoxide dismutase (SOD) and malonaldehyde (MDA). Results: TSD increased morning plasma Aβ40 levels by 32.6% (p  < 0.001) and decreased the Aβ42 /Aβ40 ratio by 19.3% (p  < 0.001). A positive relationship was found between TSD duration and plasma Aβ40 level (r  = 0.51, p  < 0.001) and Aβ40 /Aβ42 ratio (r  = 0.25, p  = 0.003). Plasma concentrations of sLRP1 (p  = 0.018) and sRAGE (p  = 0.001) decreased significantly after TSD. Aβ40 and Aβ42 plasma concentrations correlated with plasma levels of sLRP1 and sRAGE. Serum SOD decreased after TSD (p  = 0.005), whereas serum MDA was increased (p  = 0.001). Conclusion: Sleep deprivation can lead to an elevation of plasma Aβ40 and decrease of the Aβ42 /Aβ40 ratio. The underlying mechanisms may be related to increased oxidative stress and impaired peripheral Aβ clearance as pathomechanisms of AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, sleep, sleep deprivation

DOI: 10.3233/JAD-161213

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 899-906, 2017

Authors: Marwarha, Gurdeep | Rostad, Stephen | Lilek, Jaclyn | Kleinjan, Mason | Schommer, Jared | Ghribi, Othman

Article Type: Research Article

Abstract: Epidemiological studies implicate diets rich in saturated free fatty acids (sFFA) as a potential risk factor for developing Alzheimer’s disease (AD). In particular, high plasma levels of the sFFA palmitic acid (palmitate) were shown to inversely correlate with cognitive function. However, the cellular mechanisms by which sFFA may increase the risk for AD are not well known. Endoplasmic reticulum (ER) stress has emerged as one of the signaling pathways initiating and fostering the neurodegenerative changes in AD by increasing the aspartyl protease β-site AβPP cleaving enzyme 1 (BACE1) and amyloid-β (Aβ) genesis. In this study, we determined the extent to …which palmitate increases BACE1 and Aβ levels in vitro and in vivo as well as the potential role of ER stress as cellular mechanism underlying palmitate effects. We demonstrate, in palmitate-treated SH-SY5Y neuroblastoma cells and in the hippocampi of palmitate-enriched diet-fed mice, that palmitate evokes the activation of the C/EBP Homologous Protein (CHOP), a transcription factor that is specifically responsive to ER stress. Induction of CHOP expression is associated with increased BACE1 mRNA, protein and activity levels, and subsequent enhanced amyloidogenic processing of amyloid-β protein precursor (AβPP) that culminates in a substantial increase in Aβ genesis. We further show that CHOP is an indispensable molecular mediator of palmitate-induced upregulation in BACE1 activity and Aβ genesis. Indeed, we show that Chop –/– mice and CHOP knocked-down SH-SY5Y neuroblastoma cells do not exhibit the same commensurate degree of palmitate-induced increase in BACE1 expression levels and Aβ genesis. Show more

Keywords: Alzheimer’s disease, amyloid-β, β-site AβPP cleaving enzyme 1, C/EBP homologous protein, endoplasmic reticulum stress, palmitic acid, saturated free fatty acids

DOI: 10.3233/JAD-161130

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 907-925, 2017

Authors: D’Onofrio, Grazia | Sancarlo, Daniele | Ricciardi, Francesco | Panza, Francesco | Seripa, Davide | Cavallo, Filippo | Giuliani, Francesco | Greco, Antonio

Article Type: Research Article

Abstract: Background: Significant innovations have been introduced in recent years in the application of information and communication technologies (ICTs) to support healthcare for patients with dementia. Objective: In the present systematic review, our goal is to keep track of ICT concepts and approaches to support the range of activities of daily living for people with dementia and to provide a snapshot of the effect that technology is having on patients’ self-reliance. Methods: We reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. Our selection criteria included: (1) activities of daily living, …(2) ICT, and (3) dementia. Results: We identified 56 studies published between 2000 and 2015, of which 26 met inclusion criteria. The present systematic review revealed many ICT systems that could purportedly support the range of activities of daily living for patients with dementia. The results showed five research bodies: 1) technologies used by patients with dementia, 2) technologies used by caregivers, 3) monitoring systems, 4) ambient assistive living with ICTs, and 5) tracking and wayfinding. Conclusions: There is a potential for ICTs to support dementia care at home and to improve quality of life for caregivers, reducing healthcare costs and premature institutional care for these patients. Show more

Keywords: Keywords: Basic activities of daily living, dementia, information and communication technologies, instrumental activities of daily living

DOI: 10.3233/JAD-161145

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 927-935, 2017

Authors: García-Casal, J. Antonio | Goñi-Imizcoz, Miguel | Perea-Bartolomé, M. Victoria | Soto-Pérez, Felipe | Smith, Sarah Jane | Calvo-Simal, Sara | Franco-Martín, Manuel

Article Type: Research Article

Abstract: Background: The ability to recognize emotional expression is essential for social interactions, adapting to the environment, and quality of life. Emotion recognition is impaired in people with Alzheimer’s disease (AD), thus rehabilitation of these skills has the potential to elicit significant benefits. Objective: This study sought to establish whether emotion recognition capacity could be rehabilitated in people with AD. Methods: Thirty-six participants with AD were assigned to one of three conditions: an experimental group (EG) that received 20 sessions of rehabilitation of emotion recognition and 20 sessions of cognitive stimulation therapy (CST), a control group …(CG) that received 40 sessions of CST, and a treatment as usual group (TAU). Results: A positive treatment effect favoring the EG was found; participants were better able to correctly identify emotions (p  = 0.021), made fewer errors of commission (p  = 0.002), had greater precision of processing (p  = 0.021), and faster processing speed (p  = 0.001). Specifically, the EG were better able to identify sadness (p  = 0.016), disgust (p  = 0.005), and the neutral expression (p  = 0.014), with quicker processing speed for disgust (p  = 0.002). These gains were maintained at one month follow-up with the exception of processing speed for surprise, which improved. Conclusion: Capacity to recognize facial expressions of emotions can be improved through specific rehabilitation in people with AD, and gains are still present at a one month follow up. These findings have implications for the design of rehabilitation techniques for people with AD that may lead to improved quality of life and social interactions for this population. Show more

Keywords: Affect, Alzheimer’s disease, cognition, dementia, emotions, neuropsychology, rehabilitation

DOI: 10.3233/JAD-160940

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 937-951, 2017

Authors: Alosco, Michael L. | Duskin, Jonathan | Besser, Lilah M. | Martin, Brett | Chaisson, Christine E. | Gunstad, John | Kowall, Neil W. | McKee, Ann C. | Stern, Robert A. | Tripodis, Yorghos

Article Type: Research Article

Abstract: The relationship between late-life body mass index (BMI) and Alzheimer’s disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer’s Coordinating Center’s Uniform Data Set and Neuropathology Data …Set with diagnoses of normal cognition (NC; n  = 234), mild cognitive impairment (MCI; n  = 201), or AD dementia (n  = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII–VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p  = 0.3028). Analyses controlling for demographic variables and APOE ɛ 4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p  < 0.001), and in subjects with CDR of 0 (p  = 0.0021) and 0.5 (p  = 0.0012), but not ≥1.0 (p  = 0.2012). Although higher IIS predicted greater odds of ADNP (p  < 0.0001), BMI did not predict IIS (p  = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP. Show more

Keywords: Alzheimer’s disease, body mass index, cerebrovascular disease, neuropathology, obesity

DOI: 10.3233/JAD-161205

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 953-968, 2017