Journal of Alzheimer's Disease - Volume 47, issue 4

Authors: Feng, Wei | Yokoyama, Jennifer S. | Yu, Shunying | Chen, You | Cheng, Yan | Bonham, Luke W. | Wang, Dongxiang | Shen, Yuan | Wu, Wenyuan | Li, Chunbo

Article Type: Research Article

Abstract: Background: Cognitive training may contribute to the ability to maintain cognitive function in healthy elderly adults. Whether genotype modifies training effects remains unknown. Objective: Assess influence of APOE on cognitive function over time in community-dwelling elderly adults participating in multi-domain cognitive training. Methods: Healthy individuals ≥70 years of age were screened from one urban community in Shanghai. 145 healthy Chinese older adults met inclusion criteria and were assigned to intervention (n  = 88) or control (n  = 57) groups. Multi-domain cognitive training involved 24 sessions of different content taking place over 12 weeks. Neuropsychological testing was …administered at baseline, immediately after training, six months and twelve months post-intervention; composite measures of cognitive function were identified via factor analysis. Results: Three factors explained the majority of variance in function (verbal memory, processing speed, executive function). The intervention attenuated 12-month declines in processing speed, regardless of APOE genotype (p  = 0.047). Executive function declined in APOE ɛ 4 carriers over 12 months, regardless of intervention (p  = 0.056). There was a significant interaction after 12 months where intervention ɛ 4 carriers had better processing speed than ɛ 4 controls (p  = 0.003). Intervention ɛ 2 carriers had better executive function immediately after training (p  = 0.02) and had better verbal memory 6-months post-intervention (p  = 0.04). These effects remained significant after false-discovery rate correction. Conclusion: Multi-domain cognitive training reduces declines in processing speed over time. APOE ɛ 4 is associated with reductions in executive function over time, and training may attenuate ɛ 4-associated declines in processing speed. APOE ɛ 2 carriers may also benefit from training, particularly on measures of executive function and verbal memory. Show more

Keywords: Apolipoprotein E, cognitive training, elderly, neuropsychology

DOI: 10.3233/JAD-150039

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1035-1046, 2015

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

Article Type: Research Article

Abstract: The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ -secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. …The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ -secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death. Show more

Keywords: Alzheimer’s disease, amyloid-β protein precursor, β-secretase, brain ischemia, CA1 area, dementia, γ-secretase, genes, hippocampus, presenilin 1 and 2

DOI: 10.3233/JAD-150299

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1047-1056, 2015

Authors: Zhan, Ye | Chen, Kewei | Wu, Xia | Zhang, Daoqiang | Zhang, Jiacai | Yao, Li | Guo, Xiaojuan | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is one of the most serious progressive neurodegenerative diseases among the elderly, therefore the identification of conversion to AD at the earlier stage has become a crucial issue. In this study, we applied multimodal support vector machine to identify the conversion from normal elderly cognition to mild cognitive impairment (MCI) or AD based on magnetic resonance imaging and positron emission tomography data. The participants included two independent cohorts (Training set: 121 AD patients and 120 normal controls (NC); Testing set: 20 NC converters and 20 NC non-converters) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The multimodal …results showed that the accuracy, sensitivity, and specificity of the classification between NC converters and NC non-converters were 67.5% , 73.33% , and 64% , respectively. Furthermore, the classification results with feature selection increased to 70% accuracy, 75% sensitivity, and 66.67% specificity. The classification results using multimodal data are markedly superior to that using a single modality when we identified the conversion from NC to MCI or AD. The model built in this study of identifying the risk of normal elderly converting to MCI or AD will be helpful in clinical diagnosis and pathological research. Show more

Keywords: Alzheimer’s disease, classification, magnetic resonance imaging, normal elderly, positron emission tomography, support vector machine

DOI: 10.3233/JAD-142820

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1057-1067, 2015

Authors: Travassos, Maria | Santana, Isabel | Baldeiras, Inês | Tsolaki, Magda | Gkatzima, Olymbia | Sermin, Genc | Yener, Görsev G. | Simonsen, Anja | Hasselbalch, Steen G. | Kapaki, Elisabeth | Mara, Bourbouli | Cunha, Rodrigo A. | Agostinho, Paula | Blennow, Kaj | Zetterberg, Henrik | Mendes, Vera M. | Manadas, Bruno | de Mendon, Alexandreça

Article Type: Research Article

Abstract: Caffeine may be protective against Alzheimer’s disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of Aβ 1 - 42 , total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ …X - 38 , Aβ X - 40 , and Aβ X - 42 , with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15μ g/mL in the CSF and 1.20±1.88μ g/mL in the plasma. No correlation was found between caffeine consumption and Aβ 42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ 42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, caffeine, cerebrospinal fluid, metabolism, mild cognitive impairment, phosphotau, theobromine, total tau

DOI: 10.3233/JAD-150374

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1069-1078, 2015

Article Type: Meeting Report

DOI: 10.3233/JAD-150500

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1079-1084, 2015

Article Type: Other

Citation: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1085-1096, 2015