Journal of Alzheimer's Disease - Volume 41, issue 2

Authors: Leyton, Cristian E. | Savage, Sharon | Irish, Muireann | Schubert, Samantha | Piguet, Olivier | Ballard, Kirrie J. | Hodges, John R.

Article Type: Research Article

Abstract: We aimed to explore the nature of verbal repetition deficits and infer the cognitive systems involved in primary progressive aphasia (PPA) and Alzheimer's disease (AD). A total of 63 patients (13 semantic variant (sv-PPA), 17 nonfluent/agrammatic variant (nfv-PPA), 10 logopenic variant (lv-PPA), 23 AD) and 13 matched healthy controls completed a battery of tests that included naming, word comprehension, digit span, repetition of multisyllabic single words, monosyllabic word span presented under similar and dissimilar phonological conditions, and sentence repetition. All patient groups displayed some level of impairment, however, specific patterns emerged in each variant. Participants with sv-PPA were the least …impaired, showing marginal difficulties exclusively for sentence repetition, whereas those with lv-PPA had the worst overall performance. Cases with nfv-PPA showed compromised repetition of multisyllabic and phonologically similar words. The deficit in cases with AD was confined to span tasks. These distinctive patterns of language impairments can assist in the differential diagnosis of PPA variants and point toward the vulnerability of specific cognitive systems in each syndrome. Show more

Keywords: Alzheimer's disease, logopenic variant, non-fluent agrammatic variant, primary progressive aphasia, semantic variant, verbal repetition

DOI: 10.3233/JAD-132468

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 575-585, 2014

Authors: Feng, Xuemei | Bai, Zhouxian | Wang, Jiajia | Xie, Bin | Sun, Jiya | Han, Guangchun | Song, Fuhai | Crack, Peter J. | Duan, Yong | Lei, Hongxing

Article Type: Research Article

Abstract: The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to …illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional “cushion” for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn). Show more

Keywords: Brain transcriptome, disease progression, gene expression, transcriptional “cushion”

DOI: 10.3233/JAD-140147

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 587-597, 2014

Authors: Moon, Minho | Choi, Jin Gyu | Kim, Sun Yeou | Oh, Myung Sook

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is the most common cause of progressive dementia and is characterized by memory impairments, neuronal death, and neuroinflammation. AD-related pathophysiology is caused primarily by the presence of amyloid-β oligomers (AβO). Recently, an increased focus has been directed toward natural compounds or medicinal extracts for the treatment of AD. Extracts from Bombycis excrementum (BE), which is composed of various bioactive constituents and mulberry leaves (the preferred food of silkworms), have been shown to possess anti-inflammatory, anti-diabetic, and anti-oxidative effects. Additionally, mulberry leaves exert anti-amyloidogenic action and neuroprotective effects against Aβ peptides but it is unknown whether BE has …a therapeutic effect on AD-related pathologies. Therefore, the present study examined whether BE inhibits AβO-induced memory loss, neuronal death, and inflammation. Behavioral tests revealed that BE significantly ameliorated AβO-induced memory impairments and inhibited AβO-induced neuronal loss in cultured cells and the brains of mice. BE also significantly inhibited microgliosis and astrogliosis following intra-hippocampal AβO injections in mice. Furthermore, BE significantly attenuated the release of nitric oxide from microglia and reduced AβO-induced S100-β cytokine release from activated astrocytes. These results suggest that BE may be a candidate agent for the treatment of AD. Show more

Keywords: Alzheimer's disease, amyloid-β oligomer, Bombycis excrementum, cognitive impairment, neuroinflammation, neuronal death, silkworm droppings

DOI: 10.3233/JAD-140270

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 599-613, 2014

Authors: Tan, Chen-Chen | Yu, Jin-Tai | Wang, Hui-Fu | Tan, Meng-Shan | Meng, Xiang-Fei | Wang, Chong | Jiang, Teng | Zhu, Xi-Chen | Tan, Lan

Article Type: Research Article

Abstract: Background: The role of currently available drugs for Alzheimer’s disease (AD) has been controversial, with some national formularies restricting their use, and health economists questioning whether the small clinical effects are economically worthwhile. Objective: To estimate the efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of AD. Methods: Double-blind, placebo-controlled, with random assignment to a cholinesterase inhibitor or memantine trials were included into the pooled studies. Results: Cognitive effects were significant for all drugs, ranging from a −1.29 points mean difference (95% CI −2.30 to −0.28) in the 20 mg …daily memantine trials to −3.20 points (95% CI −3.28 to −3.12) in the 32 mg daily galantamine group. Only memantine had no effect on the Clinicians’ Global Impression of Change scale. No behavioral benefits were observed, except for −2.72 (95% CI −4.92 to −0.52) in the 10 mg daily donepezil group and −1.72 (95% CI −3.12 to −0.33) for 24 mg daily galantamine trial. Only 5 mg daily donepezil had no effect on the function outcome. Compared with placebo, more dropouts and adverse events occurred with the cholinesterase inhibitors, but not with memantine. Conclusions: Cholinesterase inhibitors and memantine are able to stabilize or slow decline in cognition, function, behavior, and global change. Show more

Keywords: Alzheimer's disease, donepezil, efficacy, galantamine, memantine, meta-analysis, rivastigmine, safety, systematic review

DOI: 10.3233/JAD-132690

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 615-631, 2014

Authors: Gareri, Pietro | Putignano, Daria | Castagna, Alberto | Cotroneo, Antonino Maria | De Palo, Grazia | Fabbo, Andrea | Forgione, Luigi | Giacummo, Attilio | Lacava, Roberto | Marino, Saverio | Simone, Maurizio | Zurlo, Amedeo | Putignano, Salvatore

Article Type: Research Article

Abstract: Background: Combined therapy of memantine and acetylcholinesterase inhibitors (AChEIs) in patients with Alzheimer’s disease (AD) may be associated with higher benefits than either monotherapy. Objective: This retrospective multicentric study conducted in seven Italian Ambulatory Centers for Dementia assessed the efficacy and safety of memantine 20 mg/day administered for 6 months in addition to an AChEI in AD patients with worsened cognitive functions and behavioral disorders. Methods: A total number of 240 patients (61.7% of women, 38.3% men, mean age 77.9 ± 7.32 years old) who had started treatment with the combination therapy were recruited. At baseline …(T0), Month 3 (T1), and Month 6 (T2), cognitive functions were assessed by Mini-Mental State Examination (MMSE), functional dependence by activities of daily living (ADL) and instrumental ADL, behavioral disturbances by the Neuropsychiatric Inventory (NPI), and comorbidities by Cumulative Illness Rating Scale. Adverse events were reported during the study. Results: MMSE total score significantly increased at Month 6 (p = 0.029 versus month 3) and IADL total score significantly decreased from baseline to endpoint (p = 0.033). There were no significant changes from baseline in mean ADL, despite significant improvements in NPI total score. The mean MMSE total score significantly increased with the combination donepezil + memantine compared to rivastigmine + memantine. The adverse events profile was in line with the expected range of the drugs studied and concomitant therapies. Overall, 17 patients discontinued treatment in the observation time. Conclusion: Combined treatment with memantine and AChEIs was effective in patients with AD, particularly in slowing cognitive impairment and preventing the onset of agitation and aggression in elderly AD patients. Show more

Keywords: Alzheimer's disease, acetylcholinesterase inhibitor drugs, elderly, memantine

DOI: 10.3233/JAD-132735

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 633-640, 2014

Authors: Mattace-Raso, Francesco

Article Type: Research Article

Abstract: Alzheimer's disease is the most common form of dementia in the elderly. Currently, there is no established standard treatment for this disease; therefore, the treatment of Alzheimer's disease will be a major challenge for physicians in the next decade in order to ameliorate quality of life of patients and reduce the costs for the communities.

DOI: 10.3233/JAD-140016

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 641-642, 2014

Authors: Wang, Jun | Varghese, Merina | Ono, Kenjiro | Yamada, Masahito | Levine, Samara | Tzavaras, Nikos | Gong, Bing | Hurst, William J. | Blitzer, Robert D. | Pasinetti, Giulio Maria

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by pathological aggregates of amyloid peptide-β (Aβ) and tau protein. Currently available therapies mediate AD symptoms without modifying disease progression. Polyphenol-rich diets are reported to reduce the risk for AD. Objective: In the present study, we investigated the AD disease-modifying effects of cocoa, a rich source of flavanols, which are a class of polyphenols. We hypothesized that cocoa extracts interfere with amyloid-β oligomerization to prevent synaptic deficits. Methods: We tested the effects of three different cocoa extracts, viz. Natural, Dutched, and Lavado extracts, on …Aβ42 and Aβ40 oligomerization, using photo-induced cross-linking of unmodified proteins technique. To assess the effects of cocoa extracts on synaptic function, we measured long term potentiation in mouse brain hippocampal slices exposed to oligomeric Aβ. Results: Our results indicate that cocoa extracts are effective in preventing the oligomerization of Aβ, with Lavado extract being most effective. Lavado extract, but not Dutched extract, was effective in restoring the long term potentiation response reduced by oligomeric Aβ. Conclusion: Our findings indicate that cocoa extracts have multiple disease-modifying properties in AD and present a promising route of therapeutic and/or preventative initiatives. Show more

Keywords: Amyloid, diet therapy, oligomerization, polyphenols, synapses

DOI: 10.3233/JAD-132231

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 643-650, 2014

Article Type: Other

DOI: 10.3233/JAD-140017

Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 651-653, 2014