Journal of Alzheimer's Disease - Volume 54, issue 1

Authors: Ułamek-Kozioł, Marzena | Kocki, Janusz | Bogucka-Kocka, Anna | Petniak, Alicja | Gil-Kulik, Paulina | Januszewski, Sławomir | Bogucki, Jacek | Jabłoński, Mirosław | Furmaga-Jabłońska, Wanda | Brzozowska, Judyta | Czuczwar, Stanisław J. | Pluta, Ryszard

Article Type: Research Article

Abstract: Ischemic brain damage is a pathological incident that is often linked with medial temporal lobe cortex injury and finally its atrophy. Post-ischemic brain injury associates with poor prognosis since neurons of selectively vulnerable ischemic brain areas are disappearing by apoptotic program of neuronal death. Autophagy has been considered, after brain ischemia, as a guardian against neurodegeneration. Consequently, we have examined changes in autophagy (BECN 1), mitophagy (BNIP 3), and apoptotic (caspase 3) genes in the medial temporal lobe cortex with the use of quantitative reverse-transcriptase PCR following transient 10-min global brain ischemia in rats with survival 2, 7, and 30 …days. The intense significant overexpression of BECN 1 gene was noted on the 2nd day, while on days 7–30 the expression of this gene was still upregulated. BNIP 3 gene was downregulated on the 2nd day, but on days 7–30 post-ischemia, there was a significant reverse tendency. Caspase 3 gene, associated with apoptotic neuronal death, was induced in the same way as BNIP 3 gene after brain ischemia. Thus, the demonstrated changes indicate that the considerable dysregulation of expression of BECN 1, BNIP 3, and caspase 3 genes may be connected with a response of neuronal cells in medial temporal lobe cortex to transient complete brain ischemia. Show more

Keywords: Alzheimer’s disease, BECN 1, BNIP 3, brain ischemia, caspase 3, genes, rat, selective vulnerability, temporal cortex

DOI: 10.3233/JAD-160387

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 113-121, 2016

Authors: Allali, Gilles | Garibotto, Valentina | Assal, Frèdèric

Article Type: Research Article

Abstract: Background: Parkinsonism is frequent in neurological conditions affecting gait and cognition, such as idiopathic normal pressure hydrocephalus (iNPH) and iNPH mimics, but its discriminating value between these two groups is still unidentified. Objective: This study aims to compare the prevalence of parkinsonism between iNPH and iNPH mimics and its discriminating value. Methods: Among 141 patients with suspicion of iNPH (75.7±7.1 years; 31.2% women), seventy-nine presented a possible or probable iNPH according to standardized diagnostic criteria and the remaining sixty-two were classified as iNPH mimics. Presence of parkinsonism and other seminal clinical symptoms of iNPH were …systematically evaluated by a board-certified neurologist. Covariates include age, gender, comorbidities, and white matter disease burden using the age-related white matter changes scale. Logistic regressions were used to assess the association between parkinsonism and diagnostic groups. Results: Parkinsonism was present in 40.3% of iNPH mimics and 20.3% of iNPH (p -value: 0.015). The presence of parkinsonism, but not iNPH symptoms, was associated with the diagnosis of mimics in the adjusted model (adjusted odds ratio: 2.28; 95% CI: 1.06–4.93), even when age-related white matter changes were accounted for. Conclusion: Compared to iNPH, the increased prevalence of parkinsonism in patients with iNPH mimics in the absence of significant white matter disease suggest an underlying neurodegenerative mechanism. Show more

Keywords: Aging, mimics, normal pressure hydrocephalus, parkinsonism, white matter changes

DOI: 10.3233/JAD-160428

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 123-127, 2016

Authors: Tsolaki, Magda | Karathanasi, Elina | Lazarou, Ioulietta | Dovas, Kostas | Verykouki, Eleni | Karakostas, Anastasios | Georgiadis, Kostas | Tsolaki, Anthoula | Adam, Katerina | Kompatsiaris, Ioannis | Sinakos, Zacharias

Article Type: Research Article

Abstract: There is evidence to suggest the efficacy of Crocus (saffron) in the management of cognitive decline. This study examined the efficacy of Crocus in patients with amnesic and multi domain MCI (aMCImd). The participants included 17 patients on Crocus and 18 on a waiting list, who were examined with a short neuropsychological battery, MRI 3T, while some patients were examined via 256-channel electroencephalogram (HD-EEG) at baseline and after 12 months. The results showed that patients on Crocus had improved Mini-Mental State Examination scores (p  = 0.015), while the control group deteriorated. Also, MRI, EEG, and ERP showed improvement in specific domains. …This led us to conclude that Crocus is a good choice for management of aMCImd. Show more

Keywords: Crocus sativus, electroencephalography, magnetic resonance imaging, mild cognitive impairment, saffron

DOI: 10.3233/JAD-160304

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 129-133, 2016

Authors: Li, Yan | Chang, Lirong | Song, Yizhi | Gao, Xianghong | Roselli, Francesco | Liu, Jinping | Zhou, Wei | Fang, Yuan | Ling, Wei | Li, Hui | Almeida, Osborne F.X. | Wu, Yan

Article Type: Research Article

Abstract: Early-stage Alzheimer’s disease (AD) is characterized by synaptic dysfunction, a phenomenon in which soluble oligomers of amyloid-beta (Aβ) and N-methyl-D-aspartate receptor (NMDAR) are implicated. Here, we demonstrated that astrocytes express NMDARs and therefore have the potential to modulate the synaptotoxic actions of Aβ. We found that specific pharmacological antagonism of two of the major NMDAR subunits, GluN2A and GluN2B, exacerbates Aβ-induced synaptotoxicity suggesting, for the first time, that astrocytic GluN2A and GluN2B mediate synaptoprotection. From the perspective of the pathogenic mechanisms of Alzheimer’s disease, in which Aβ and NMDAR play significant roles, these observations are striking since neuronal GluN2A and …GluN2B are well known modulators of neurodegeneration. We did initial studies to understand the basis for the differential effects of astrocytic and neuronal GluN2A and GluN2B in the promotion of synapse survival, and identified a neurotrophin produced by astrocytes, nerve growth factor β (β-NGF), as a likely mediator of the synaptoprotective effects of astrocytic GluN2A and GluN2B activation. The results presented suggest that astrocytes may be suitable druggable targets for the prevention and/or delay of the synaptic loss that occurs during early stages of AD. Show more

Keywords: Amyloid-beta, astrocyte, N-methyl-D-aspartate receptors, synaptotoxicity

DOI: 10.3233/JAD-160297

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 135-148, 2016

Authors: Connors, Michael H. | Ames, David | Boundy, Karyn | Clarnette, Roger | Kurrle, Sue | Mander, Alastair | Ward, John | Woodward, Michael | Brodaty, Henry

Article Type: Research Article

Abstract: Background: Patients with mild cognitive impairment (MCI) are at greater risk of mortality than the general population. Comparatively little research has examined predictors of mortality in MCI and no research has examined whether time-varying variables, such as change in cognition and function, predict survival. Objective: To identify predictors of mortality in patients with MCI. Methods: 185 patients with MCI were recruited from nine memory clinics around Australia. Patients completed measures of cognition, function, and neuropsychiatric symptoms over three years. Mortality data were obtained from state registries eight years after baseline. Results: 55 (30%) …patients died within this period. Older age, lower cognitive and functional ability at baseline, and greater decline in functional ability over six months predicted mortality. Conclusion: Easily measurable clinical data predict mortality in patients with MCI. Longitudinal assessment over time can provide additional information about patients’ risk. Show more

Keywords: Lifespan, longitudinal studies, mild cognitive impairment, mortality, risk factors, survival

DOI: 10.3233/JAD-160148

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 149-155, 2016

Authors: Mandecka, Monika | Budziszewska, Magdalena | Barczak, Anna | Pepłońska, Beata | Chodakowska-Żebrowska, Małgorzata | Filipek-Gliszczyńska, Anna | Nesteruk, Marta | Styczyńska, Maria | Barcikowska, Maria | Gabryelewicz, Tomasz

Article Type: Research Article

Abstract: In the course of Alzheimer’s disease (AD), early pathological changes in the brain start decades before any clinical manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-β1-42 (Aβ1-42 ), total tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer’s dementia (AD-D), together with the relationships between the biomarkers, an APOE ɛ …4 presence, and a verbal episodic memory performance. We included 252 patients from the memory clinic with a diagnosis of SCD (n  = 85), MCI (n  = 87), and AD-D (n  = 80). A verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly lower levels of Aβ1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE ɛ 4 carriers, who had lower levels of Aβ1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly higher in the APOE ɛ 4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole study samples was predicted by age, Aβ1-42 , and the T-tau CSF biomarkers, but not by the APOE genotyping. Show more

Keywords: Alzheimer’s disease, APOE genotype, auditory verbal learning task, cerebrospinal fluid biomarkers, diagnosis, mild cognitive impairment, subjective cognitive decline

DOI: 10.3233/JAD-160176

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 157-168, 2016

Authors: Grinberg, Lea T. | Anghinah, Renato | Nascimento, Camila Fernandes | Amaro Jr, Edson | Leite, Renata P. | Martin, Maria da Graça M. | Naslavsky, Michel S. | Takada, Leonel T. | Filho, Wilson Jacob | Pasqualucci, Carlos A. | Nitrini, Ricardo

Article Type: Research Article

Abstract: The relationship between soccer and chronic traumatic encephalopathy (CTE) is not well established. We report clinicopathological correlations in an 83-year-old retired center-back soccer player, with no history of concussion, manifesting typical Alzheimer-type dementia. Examination revealed mixed pathology including widespread CTE, moderate Alzheimer’s disease, hippocampal sclerosis, and TDP-43 proteinopathy. This case adds to a few CTE cases described in soccer players. Furthermore, it corroborates that CTE may present clinically as typical Alzheimer-type dementia. Further studies investigating the extent to which soccer is a risk for CTE are needed.

Keywords: Alzheimer’s disease, autopsy, chronic post-traumatic encephalopathy, dementia, humans, soccer

DOI: 10.3233/JAD-160312

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 169-174, 2016

Authors: Sun, Jie | Cai, Rongrong | Huang, Rong | Wang, Pin | Tian, Sai | Sun, Haixia | Xia, Wenqing | Wang, Shaohua

Article Type: Research Article

Abstract: Background: Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. Objective: We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. Methods: We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. Results: There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among …diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r  = –0.638; p  < 0.001). Negative correlations were also found between the serum CETP concentration with the Auditory Verbal Learning Test (r  = –0.266; p  = 0.008), indicating memory deficit. Logistic regression analysis revealed that CETP concentration was an independent factor of diabetic MCI (p  < 0.001). Further stratification study showed that high serum levels of CETP was an independent risk factor of MCI in diabetic patients with a low density lipoproteins level ≥2.59 mmol/L, or high density lipoproteins level ≤1.0 mmol/L for men and ≤1.3 mmol/L for women, or TG level ≥1.7 mmol/L, after adjusting for age, sex, education, and glucose control (all p s < 0.05). Conclusions: CETP was intimately involved in dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients. Show more

Keywords: Cholesteryl ester transfer protein, dyslipidemia, memory decline, mild cognitive impairment, type 2 diabetes

DOI: 10.3233/JAD-160053

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 175-184, 2016

Authors: Heser, Kathrin | Bleckwenn, Markus | Wiese, Birgitt | Mamone, Silke | Riedel-Heller, Steffi G. | Stein, Janine | Lühmann, Dagmar | Posselt, Tina | Fuchs, Angela | Pentzek, Michael | Weyerer, Siegfried | Werle, Jochen | Weeg, Dagmar | Bickel, Horst | Brettschneider, Christian | König, Hans-Helmut | Maier, Wolfgang | Scherer, Martin | Wagner, Michael | for the AgeCoDe Study Group

Article Type: Research Article

Abstract: Background: Late-life depression is frequently accompanied by cognitive impairments. Objective: Whether these impairments indicate a prodromal state of dementia, or are a symptomatic expression of depression per se is not well-studied. Methods: In a cohort of very old initially non-demented primary care patients (n  = 2,709, mean age = 81.1 y), cognitive performance was compared between groups of participants with or without elevated depressive symptoms and with or without subsequent dementia using ANCOVA (adjusted for age, sex, and education). Logistic regression analyses were computed to predict subsequent dementia over up to six years of follow-up. The same analytical approach …was performed for lifetime major depression. Results: Participants with elevated depressive symptoms without subsequent dementia showed only small to medium cognitive deficits. In contrast, participants with depressive symptoms with subsequent dementia showed medium to very large cognitive deficits. In adjusted logistic regression models, learning and memory deficits predicted the risk for subsequent dementia in participants with depressive symptoms. Participants with a lifetime history of major depression without subsequent dementia showed no cognitive deficits. However, in adjusted logistic regression models, learning and orientation deficits predicted the risk for subsequent dementia also in participants with lifetime major depression. Conclusion: Marked cognitive impairments in old age depression should not be dismissed as “depressive pseudodementia”, but require clinical attention as a possible sign of incipient dementia. Non-depressed elderly with a lifetime history of major depression, who remained free of dementia during follow-up, had largely normal cognitive performance. Show more

Keywords: Cognition, dementia, depression, depressive symptoms, executive function, memory

DOI: 10.3233/JAD-160209

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 185-199, 2016

Authors: Johnson, Leigh A. | Gamboa, Adriana | Vintimilla, Raul | Edwards, Melissa | Hall, James | Weiser, Brent | Yadav, Menaka | Dickensheets, Tony | O’Bryant, Sid E.

Article Type: Research Article

Abstract: Background: Late life depression is a prodromal feature and a risk factor for Alzheimer’s disease (AD) and mild cognitive impairment (MCI). We identified five items in the Geriatric Depression scale (DepE) that are important as a risk for MCI and AD: memory problems, feeling blue, crying, feeling worthless, and trouble concentrating. Objective: Our goal was to examine the relationship between DepE and cognition in a cohort of Mexican Americans. Methods: Data from 317 Mexican Americans from the HABLE study were analyzed. DepE scores were dichotomized into two groups: endorsement of 1 item or less, and …endorsement of 2 or more items. Cognition was assessed via neuropsychological tests, and diagnosis was based on consensus review. We utilized linear regression to examine the association between DepE and cognitive performance, and logistic regression to examine the utility of DepE in predicting MCI. To examine the impact of DepE on memory over 12 months, we performed ANOVA analysis. Results: Elevated DepE scores were associated with poorer performance on various measures of memory and cognition, but not executive or visual spatial skills. Over 12 months, we found a decline in immediate memory among women but not men. Those with high scores were 4 times more likely to have MCI. ANOVA of total scores revealed differences between groups on immediate memory (p  < 0.05) in women, with no significant differences on delay recall in either gender. Conclusion: DepE can be utilized in Mexican Americans to identify those at risk of memory related cognitive decline. Show more

Keywords: Alzheimer’s disease, cognitive decline, depression, endophenotype, Mexican American, mild cognitive impairment

DOI: 10.3233/JAD-150743

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 201-206, 2016