Journal of Alzheimer's Disease - Volume 63, issue 2

Authors: Dekker, Alain D. | Sacco, Silvia | Carfi, Angelo | Benejam, Bessy | Vermeiren, Yannick | Beugelsdijk, Gonny | Schippers, Mieke | Hassefras, Lyanne | Eleveld, José | Grefelman, Sharina | Fopma, Roelie | Bomer-Veenboer, Monique | Boti, Mariángeles | Oosterling, G. Danielle E. | Scholten, Esther | Tollenaere, Marleen | Checkley, Laura | Strydom, André | Van Goethem, Gert | Onder, Graziano | Blesa, Rafael | zu Eulenburg, Christine | Coppus, Antonia M.W. | Rebillat, Anne-Sophie | Fortea, Juan | De Deyn, Peter P.

Article Type: Research Article

Abstract: People with Down syndrome (DS) are prone to develop Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. 83 behavioral items in 12 clinically defined sections were evaluated. The central aim was to identify items that change in relation to the dementia status, and thus may differentiate between diagnostic groups. Structured interviews were conducted …with informants of persons with DS without dementia (DS, n  = 149), with questionable dementia (DS+Q, n  = 65), and with diagnosed dementia (DS+AD, n  = 67). First exploratory data suggest promising interrater, test-retest, and internal consistency reliability measures. Concerning item relevance, group comparisons revealed pronounced increases in frequency and severity in items of anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and eating/drinking behavior. The proportion of individuals presenting an increase was highest in DS+AD, intermediate in DS+Q, and lowest in DS. Interestingly, among DS+Q individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy, and depressive symptoms, suggesting that these changes occur early in the course of AD. Future efforts should optimize the scale based on current results and clinical experiences, and further study applicability, reliability, and validity. Future application of the scale in daily care may aid caregivers to understand changes, and contribute to timely interventions and adaptation of caregiving. Show more

Keywords: Alzheimer’s disease, behavior, BPSD, dementia, Down syndrome, neuropsychiatric symptoms, trisomy 21

DOI: 10.3233/JAD-170920

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 797-819, 2018

Authors: Basurto-Islas, Gustavo | Gu, Jin-hua | Tung, Yunn Chyn | Liu, Fei | Iqbal, Khalid

Article Type: Research Article

Abstract: Dementias including Alzheimer’s disease (AD) are multifactorial disorders that involve several different etiopathogenic mechanisms. Cerebral ischemia has been suspected in the altered regulation of protein kinases and phosphatases that leads to hyperphosphorylation of tau and further neurofibrillary pathology, a key hallmark of AD and related neurodegenerative diseases. However, the deregulation of these enzymes and their relationship with ischemia and AD remain unclear. Previously, we reported a mechanism by which the lysosomal enzyme asparagine endopeptidase (AEP) is associated with brain acidosis and AD. In this study, we subjected mice to middle cerebral artery occlusion and found that compared with wild type …mice, the ischemia-induced brain injury and motor deficit in AEP-knockout mice are reduced, probably because ischemia activates AEP. AEP cleaves inhibitor 2 of protein phosphatase 2A (I2 PP2A), which translocates from the neuronal nucleus to the cytoplasm and produces hyperphosphorylation of tau through inhibition of PP2A. These findings suggest a possible mechanism of tau pathology associated with ischemia. Show more

Keywords: Alzheimer’s disease, asparagine endopeptidase, ischemia, tau

DOI: 10.3233/JAD-170715

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 821-833, 2018

Authors: Wang, Jiaqi | Yuan, Yang | Cai, Rongrong | Huang, Rong | Tian, Sai | Lin, Hongyan | Guo, Dan | Wang, Shaohua

Article Type: Research Article

Abstract: Background: Plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) are involved in the complications of type 2 diabetes mellitus (T2DM) and early pathology of Alzheimer’s disease. Objective: This study aimed to investigate the association between plasma PAI-1, tPA/PAI-1 molar ratio, and mild cognitive impairment (MCI) in Chinese T2DM patients. Methods: A total of 162 Chinese T2DM patients were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma PAI-1 and tPA levels were measured through enzyme-linked immunosorbent assay, tPA/PAI-1 molar ratio was calculated, and neuropsychological test …results were examined. The association between PAI-1, tPA/PAI-1 molar ratio, and cognition was analyzed. Results: There were 66 diabetic MCI patients and 96 healthy cognition participants (controls). T2DM patients with MCI displayed significantly increased plasma PAI-1 levels (p  = 0.016) and decreased tPA/PAI-1 molar ratio (p  = 0.021) compared with the controls. High PAI-1 levels and low tPA/PAI-1 molar ratio were associated with MCI in T2DM patients, e.g., plasma level of PAI-1 were negatively correlated (r  = –0.343, p  = 0.007) with logic memory in T2DM patients with MCI. Linear regression analysis further revealed that PAI-1 concentration was an independent factor of diabetic MCI (p  = 0.001). Conclusions: High PAI-1 levels and low tPA/PAI-1 molar ratio were significantly correlated with T2DM-associated cognitive impairment, especially memory function, in Chinese patients. Show more

Keywords: Memory, mild cognitive impairment, PAI-1, tPA/PAI-1, type 2 diabetes mellitus

DOI: 10.3233/JAD-171038

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 835-845, 2018

Authors: Vojdani, Aristo | Vojdani, Elroy | Saidara, Evan | Kharrazian, Datis

Article Type: Research Article

Abstract: As early as the 1980s, molecular virologist Ruth Itzhaki began to investigate if there was a causal connection between infections and neurodegenerative disorder. Although the theory has yet to be universally embraced, in 2016 Itzhaki and 33 other scientists from all over the world published a review article in this very journal presenting evidence for the causal role of pathogens in Alzheimer’s disease (AD). Exactly how and in what way pathogens affect the induction of AD has yet to be determined, but one possible answer may involve the cross-reactivity of different pathogens with amyloid-β (Aβ). Aβ autoantibodies have been detected …in the serum and cerebrospinal fluid of AD patients and in some healthy individuals. In the present study our major goal was to investigate whether antibodies made against Aβ would react both with other brain proteins as well as pathogens associated with AD as a result of molecular mimicry or the binding of bacterial toxins to Aβ42 . Our study used a specific monoclonal antibody made against Aβ42 , which not only reacted strongly with Aβ42 , tau protein, and α-synuclein, but also had from weak to strong reactions with 25 different pathogens or their molecules, some of which have been associated with AD. The homology between peptide stretches of microbial origin and proteins involved in AD could be a mechanism by which antibodies to homologous peptides mount attacks against autoantigens in AD. We concluded that bacterial molecules bind to Aβ protein, forming small oligomers, then encasing pathogens and their molecules to form amyloid plaques, the tell-tale markers of AD. Conversely, these same Aβ peptides induce the production of antibodies to both Aβ42 and bacterial molecules, which may inhibit bacterial pathogenesis, but in the process may promote amyloid plaque formation. Show more

Keywords: Alzheimer’s disease, amyloid-β, autoantibody, molecular mimicry, pathogens

DOI: 10.3233/JAD-170961

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 847-860, 2018

Authors: Wada, Masataka | Noda, Yoshihiro | Shinagawa, Shunichiro | Chung, Jun Ku | Sawada, Kyosuke | Ogyu, Kamiyu | Tarumi, Ryosuke | Tsugawa, Sakiko | Miyazaki, Takahiro | Yamagata, Bun | Graff-Guerrero, Ariel | Mimura, Masaru | Nakajima, Shinichiro | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Cognitive reserve is the acquired capacity reflecting a functional brain adaptability/flexibility in the context of aging. Educational attainment is thought to be among the most important factors that contribute to cognitive reserve. Objective: The aim of this study is to investigate the relationships among duration of education and Alzheimer’s disease (AD) related neuroimaging biomarkers such as amyloid-β deposition, glucose metabolism, and brain volumes in each stage of AD. Methods: We reanalyzed a part of the datasets of the Alzheimer’s Disease Neuroimaging Initiative. Participants were between 55 and 90 years of age and diagnosed as one …of the following: healthy controls (HC), mild cognitive impairment (MCI), or AD. Multiple regression analyses were conducted to examine the relationships among duration of education and amyloid-β deposition (n  = 825), brain metabolism (n  = 1,304), and brain volumes (n  = 1,606) among three groups using data for 18 F-Florbetapir (AV-45) imaging, fludeoxyglucose (FDG) positron emission tomography, and T1-weighted magnetic resonance imaging. Results: Duration of education had no correlations with amyloid-β deposition or brain metabolism in any groups. However, duration of education was positively associated with the total brain volume only in participants with MCI. Conclusions: Our findings suggest that education may exert a protective effect on total brain volume in the MCI stage but not in HC or AD. Thus, education may play an important role in preventing the onset of dementia through brain reserve in MCI. Show more

Keywords: Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative (ADNI), brain reserve, brain volume, cognitive reserve, education, mild cognitive impairment

DOI: 10.3233/JAD-171168

Citation: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 861-869, 2018