Journal of Alzheimer's Disease - Volume 69, issue 3

Authors: Mendez, Mario F. | Monserratt, Lorena H. | Liang, Li-Jung | Chavez, Diana | Jimenez, Elvira E. | Maurer, Joseph J. | Laffey, Megan

Article Type: Research Article

Abstract: Background: The neuropsychological recognition of early-onset Alzheimer’s disease (AD) can be difficult because of non-amnestic variants such as logopenic variant primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA). Objective: This study evaluated the similarities and differences between typical amnestic AD (tAD) and lvPPA and PCA on a screening neuropsychological battery. Methods: We enrolled 51 patients meeting NIA-AA criteria for biomarker-supported AD (amnestic or non-amnestic) and having an age of onset of <65 years of age. Based on additional recommended clinical criteria for lvPPA and PCA, the early-onset AD patients were divided into three groups (28 …tAD, 9 lvPPA, 14 PCA) of comparable age and dementia severity. We then analyzed their profiles on a focused, screening neuropsychological battery for early-onset AD. Results: In addition to greater variance on the Mini-Mental State Examination, the lvPPA and PCA variants had episodic memory impairment that did not significantly differ from the memory impairment in the tAD patients. Despite differences on language and visuospatial tasks, they did not significantly distinguish the lvPPA and PCA from tAD. The lvPPA group, however, was distinguishable by worse performance on measures reflecting working memory (digit span forward, memory registration). Conclusions: On neuropsychological screening, all clinical early-onset AD subtypes may have memory impairments. Screening batteries for early-onset AD should also include measures of working memory, which is disproportionately decreased in lvPPA. Show more

Keywords: Alzheimer’s disease, logopenic variant primary progressive aphasia, posterior cortical atrophy, working memory

DOI: 10.3233/JAD-190124

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 849-855, 2019

Authors: Golchert, Johannes | Roehr, Susanne | Luck, Tobias | Wagner, Michael | Fuchs, Angela | Wiese, Birgitt | van den Bussche, Hendrik | Brettschneider, Christian | Werle, Jochen | Bickel, Horst | Pentzek, Michael | Oey, Anke | Eisele, Marion | König, Hans-Helmut | Weyerer, Siegfried | Mösch, Edelgard | Maier, Wolfgang | Scherer, Martin | Heser, Kathrin | Riedel-Heller, Steffi G.

Article Type: Research Article

Abstract: Background: Sex differences in verbal episodic memory function have been widely reported. However, sex-specific effects on rates of episodic memory decline remain controversial, and evidence is particularly scarce in the oldest-old population. Objective: We aimed to investigate sex differences in trajectories of episodic memory performance in oldest-old individuals. Methods: Based on 13-year longitudinal data with 9 follow-up assessments of a large sample of cognitively unimpaired old (75+) primary care patients (n  = 3,254) participating in the German AgeCoDe/AgeQualiDe study, we used linear mixed effects analyses to model sex-specific trajectories of change in verbal episodic memory while accounting …for covarying factors. Results: We found that even in the highest age group women outperformed men in immediate (b  = –1.71, p  < 0.001) and delayed (b  = –0.85, p  < 0.001) free recall conditions. Associated late-life trajectories, however, did not differ significantly between the sexes. We further demonstrated that younger age, higher education, and an absence of depressive symptoms predicted better performance in both sexes. In contrast, past occurrences of stroke and APOE ɛ 4 carrier status showed a negative relation to test scores. Conclusion: Our findings confirm previous research suggesting that women perform better in verbal episodic memory tests. We add that this advantage is still present in the oldest-old age groups. Our results indicate that sociodemographic and health related factors are as important as genetically based APOE ɛ 4 carrier status in the prediction of normal cognitive development in advanced old age. Show more

Keywords: Cognition, cohort study, longitudinal, oldest-old, sex differences, verbal episodic memory

DOI: 10.3233/JAD-180949

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 857-869, 2019

Authors: Li, Jianyuan | Liu, Weidong | Yao, Weicheng

Article Type: Research Article

Abstract: Cerebral ischemic stroke may cause a number of adverse neurological complications or behavioral disorders. Moreover, cerebral ischemic stroke is a prevalent disease with limited treatment strategies and may increase chances of developing neurodegenerative diseases, e.g., Alzheimer’s disease, in the future. Therefore, alternative strategies are highly needed for improving the therapy for ischemic stroke. Human bone marrow stroma stem cells, also known as mesenchymal stem cells (hMSC), have a demonstrative role in treating transient cerebral ischemia, yet whether immortalized hMSC may have a better effect than hMSC is unknown. Here, we addressed this question. A rat cerebral ischemia reperfusion (IR) model …was used to compare the effects of hMSC and an immortalized hMSC by human telomerase reverse transcriptase (hMSC-TERT). We found that both hMSC and hMSC-TERT similarly attenuated the elevation of serum neuron specific enolase levels after IR. Transplantation with hMSC alleviated cerebral infarction, alleviated brain edema, improved neural function, and reduced brain cell apoptosis, in a significantly better degree than transplantation with hMSC. Thus, these data suggest that immortalized hMSC may have an advantage over hMSC in treatment of transient cerebral ischemia. Show more

Keywords: Apoptosis, cerebral ischemia reperfusion, human bone marrow stroma stem cells

DOI: 10.3233/JAD-190279

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 871-880, 2019

Authors: Guo, Yanfang | Yu, Haining

Article Type: Research Article

Abstract: Background: Several observational studies have found leukocyte telomere length (TL) to be associated with Alzheimer’s diseases (AD) or dementia. However, these findings were based on small sample sizes and cannot clarify whether this relationship was causal. Genome-wide association studies (GWAS) have identified common variants associated with TL, providing a valuable resource for examining the causal effect of TL on AD using Mendelian Randomization (MR) methods. Objective: To examine if TL was causally associated with AD using GWAS summary statistics. Methods: Using a genetic risk score comprised of seven variants associated with leukocyte TL as an instrumental …variable, we tested whether shorter TL was associated with a higher risk of AD by applying an MR approach to the summarized genome-wide association study data. Results: The genetic risk score for TL was associated with higher risk of AD [log-odds ratio (OR) = 0.003 for per TL-decreasing allele; 95% confidence interval (CI): 0.001, 0.005, p  = 0.005]. Moreover, the MR analysis provided support for shorter TL to be causally associated with a higher risk of AD (log-OR = 0.04 per SD-decrease of TL; 95% CI: 0.01, 0.08, p  = 0.01). Conclusion: We suggest that TL has a causal effect on the risk of AD. Show more

Keywords: Alzheimer’s disease, genetics, telomere length

DOI: 10.3233/JAD-190134

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 881-885, 2019

Authors: Teichmann, Marc | Daigmorte, Chloé | Funkiewiez, Aurélie | Sanches, Clara | Camus, Maeva | Mauras, Thomas | Le Ber, Isabelle | Dubois, Bruno | Levy, Richard | Azuar, Carole

Article Type: Research Article

Abstract: Background: Emotions, with or without moral valence, appear to be altered in the behavioral variant of frontotemporal dementia (bvFTD) but the relative degree of moral emotion breakdown, which could be a marker of bvFTD diagnosis, remains unexplored. Objective: To assess moral emotions in bvFTD, to differentiate bvFTD from typical Alzheimer’s disease (AD) based on moral emotion processing, and to provide a sensitive and specific assessment tool contributing to bvFTD diagnosis. Methods: We investigated moral emotions in 22 bvFTD patients, 15 patients with typical AD having positive CSF AD biomarkers, and 45 healthy controls. The ‘Moral Emotions …Assessment’ task consisted in 42 scenarios exploring positive and negative moral emotions. To control for moral-specificity, we contrasted the 42 moral scenarios with 18 extra-moral scenarios eliciting the emotions without involving any inter-human moral context. Results: bvFTD patients were more impaired in emotion processing than AD patients and healthy controls and had significantly poorer performance in the processing of moral emotions than of emotions without moral valence. ROC analyses of data on moral scenarios showed a high area under the curve (83%), and indicated a cut-off score (< 37/42) for differentiating bvFTD from AD with a sensitivity of 82% and specificity of 73%. Conclusion: Our findings demonstrate that bvFTD patients have disorders in emotion processing which is mainly related to failure regarding moral emotions. They also show that this deficit is reliably detected by the ‘Moral Emotions Assessment’ which represents a sensitive and specific diagnostic tool detecting bvFTD and differentiating it from AD. Show more

Keywords: Alzheimer’s disease, frontotemporal dementia, moral emotions

DOI: 10.3233/JAD-180991

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 887-896, 2019