Journal of Alzheimer's Disease - Volume 16, issue 3

Authors: Sorensen, Aaron A.

Article Type: Research Article

Abstract: The online availability of scientific-literature databases and natural-language-processing (NLP) algorithms has enabled large-scale bibliometric studies within the field of scientometrics. Using NLP techniques and Thomson ISI reports, an initial analysis of the role of Alzheimer’s disease (AD) within the neurosciences as well as a summary of the various research foci within the AD scientific community are presented. Citation analyses and productivity filters are applied to post-1984, AD-specific subsets of the PubMed and Thomson ISI Web-of-Science literature bases to algorithmically identify a pool of the top AD researchers. From the initial pool of AD investigators, top-100 rankings are compiled to assess …productivity and impact. One of the impact and productivity metrics employed is an AD-specific H-index. Within the AD-specific H-index ranking, there are many cases of multiple AD investigators with similar or identical H-indices. In order to facilitate differentiation among investigators with equal or near-equal H indices, two derivatives of the H-index are proposed: the Second-Tier H-index and the Scientific Following H-index. Winners of two prestigious AD-research awards are highlighted, membership to the Institute of Medicine of the US National Academy of Sciences is acknowledged, and an analysis of highly-productive, high-impact, AD-research collaborations is presented. Show more

Keywords: Alzheimer’s disease, amyloid-β, amyloid-β protein precursor, citation, citation analysis, H-index, highly-cited, history of science, neurodegenerative diseases, oxidative stress, Scientific following H, scientometrics, Second-tier H-index, tau

DOI: 10.3233/JAD-2009-1046

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 451-465, 2009

Authors: Panza, Francesco | Frisardi, Vincenza | Capurso, Cristiano | D'Introno, Alessia | Colacicco, Anna M. | Vendemiale, Gianluigi | Capurso, Antonio | Solfrizzi, Vincenzo

Article Type: Letter

Abstract: Very recent findings confirmed that S-adenosylmethionine (SAM) can exert a direct effect on glutathione S-transferase (GST) activity. Alzheimer's disease (AD) is accompanied by reduced GST activity, diminished SAM, and increased S-adenosyl homocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement in AD. Given recent findings from clinical trials in which ω-3 polyunsturated fatty acids (PUFA) supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), …we suggest intervention trials using measures of dietary supplementation (dietary ω-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation, and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own. Show more

Keywords: Alzheimer's disease, mild cognitive impairment, ω-3 polyunsturated fatty acids, S-Adenosylhomocysteine, S-Adenosylmethionine

DOI: 10.3233/JAD-2009-1012

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 467-470, 2009

Authors: Lovell, Mark A.

Article Type: Review Article

Abstract: Although multiple studies have suggested a role for alterations of zinc (Zn) and zinc transport (ZnT) proteins in the pathogenesis of Alzheimer's disease, the exact role of this essential trace element in the progression of the disease remains unclear. The following review discusses the normal role of Zn and ZnT proteins in brain and the potential effects of their alteration in the pathogenesis of Alzheimer's disease, particularly in the processing of the amyloid-β protein precursor and amyloid-β peptide generation and aggregation.

Keywords: Amyloid-β, early Alzheimer's disease, mild cognitive impairment, zinc, zinc transport proteins

DOI: 10.3233/JAD-2009-0992

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 471-483, 2009

Authors: Salmina, Alla B.

Article Type: Review Article

Abstract: Accumulating evidence suggests that alterations of neuron-glia interactions are associated with development of neurodegenerative diseases referred to as taupathies. Astrocytes contribute to a variety of functions of neurons, including synapse formation and plasticity, energetic and redox metabolism, and synaptic homeostasis of neurotransmitters and ions. Microglia represent the immune system of the brain and therefore are critically involved in various injuries and diseases. Oligodendrocytes have a role in regulation of steroid synthesis which is important for neuroprotection against degeneration. Glia-mediated inflammatory response is involved in dramatic changes in activity of neuritic plaque-associated astrocytes and microglia, and the link between glial activation …and neuronal damage or repair has been postulated. In addition, functional relationship between neurons, glial cells, and vascular cells within so-called neurovascular unit is dramatically compromised in Alzheimer's disease. Therefore, importance of alterations in synergistic interactions between the cells in pathogenesis of this neurodegenerative disorder has been suggested. Further understanding of molecular mechanisms of neuron-glia interactions in Alzheimer's disease would give us novel diagnostic and therapeutic strategies. Show more

Keywords: Alzheimer disease, glia-mediated response, neuron-glia interactions, neurovascular unit

DOI: 10.3233/JAD-2009-0988

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 485-502, 2009

Authors: Tan, Zaldy S. | Vasan, Ramachandran S.

Article Type: Review Article

Abstract: Thyroid dysfunction has been implicated as a cause of reversible cognitive impairment and as such, the thyroid stimulating hormone has long been part of the screening laboratory test for dementia. Recently, several population-based studies demonstrated an association between hypo- or hyperthyroidism and Alzheimer's disease. This review discusses the role of thyroid hormone in the normal development and regulation of central nervous system functions and summarizes the studies that have linked thyroid function and dementia risk. Finally, it explores possible biological mechanisms to explain this association, including the direct effects of thyroid hormone on cerebral amyloid processing, neurodegeneration and thyrotropin-mediated mechanisms …and vascular mediated enhancement of Alzheimer's disease risk. Show more

Keywords: Alzheimer's disease, dementia, hyperthyroidism, hypothyroidism, thyroid

DOI: 10.3233/JAD-2009-0991

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 503-507, 2009

Authors: Marcon, Gabriella | Di Fede, Giuseppe | Giaccone, Giorgio | Rossi, Giacomina | Giovagnoli, Anna Rita | Maccagnano, Elio | Tagliavini, Fabrizio

Article Type: Short Communication

Abstract: Presenilin mutations are the main cause of familial Alzheimer's disease. So far, more than 160 mutations in the Presenilin 1 gene (PSEN1) and approximately 10 mutations in the homologous Presenilin 2 gene (PSEN2) have been identified. Some PSEN1 mutations are associated with a phenotype fulfilling the clinical criteria of frontotemporal dementia. In PSEN2, T122P and M239V mutations presented with severe behavioral disturbances. We describe an Italian patient with a novel PSEN2 mutation (Y231C) who showed behavioral abnormalities and language impairment as presenting symptoms, with later involvement of other cognitive abilities, particularly of posterior functions.

Keywords: Alzheimer's disease, atypical phenotype, familial, mutation, presenilin 2

DOI: 10.3233/JAD-2009-0986

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 509-511, 2009

Authors: Nacmias, Benedetta | Tedde, Andrea | Bagnoli, Silvia | Cellini, Elena | Guarnieri, Bianca Maria | Piacentini, Silvia | Sorbi, Sandro

Article Type: Short Communication

Abstract: A common polymorphism (rs2373115) in the GRB-associated binding protein 2 (GAB2) gene has been recently associated with the risk of developing Alzheimer's disease (AD) in 644 apolipoprotein E (ApoE) ε4 carriers. In order to assess the involvement of the GAB2 polymorphism in the risk of developing AD, we analyzed the genotype and allele distributions of the GAB2 rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of GAB2 genetic variant in AD. However, the observed association was confined to ApoE ε4 non-carriers, thus suggesting a possible role of GAB2 as an independent risk factor for AD.

Keywords: Alzheimer's disease, apolipoprotein E, genetic determinant, GRB-associated binding protein 2

DOI: 10.3233/JAD-2009-1005

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 513-515, 2009

Authors: Hoffmann, Michael | Muniz, Juan | Carroll, Elizabeth | De Villasante, Jorge

Article Type: Short Communication

Abstract: A sixty-two year old man, with a background of Alzheimer's disease for the past three years, acutely presented with imbalance, headaches, and dizziness. Examination revealed a profound frontal disinhibited and dysexecutive syndrome and brain imaging notable for leptomeningeal enhancement; laboratory data confirmed cryptococcal meningitis. Four months after treatment, the patient was normal neurologically, cognitively and neuroradiologically. The specific cognitive impairment and neuroradiological findings may be clues to differing dementia etiologies.

Keywords: Cryptococcal meningitis, dementia, frontal syndrome

DOI: 10.3233/JAD-2009-0985

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 517-520, 2009

Authors: Sabayan, Behnam | Namazi, Mohammad Reza | Mowla, Arash | Moniri, Seyyed Alireza

Article Type: Research Article

Abstract: Calcium is one of the most important intracellular messengers in human brain. Studies show that there is a relationship between altered Ca2+ -homeostasis, especially elevation of intracellular calcium, and formation of the hallmark pathological lesions of Alzheimer's disease. Additionally, Ca2+ is crucial for normal function of the skin, and an abnormal rise in intracellular Ca2+ can consequently lead to the development of two skin disorders: Darier and Hailey-Hailey diseases. As these mutated genes are also highly expressed in the brain and these patients are reported to experience some neuropsychiatric problems, we have hypothesized that patients with these dermatologic …diseases may be more prone to the development of Alzheimer's disease. Further investigation may give us clues to find novel therapeutic targets and agents for modulation of intracellular calcium in neurons. Show more

Keywords: Alzheimer's disease, Darier disease, Hailey-Hailey disease, intracellular calcium

DOI: 10.3233/JAD-2009-0956

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 521-523, 2009

Authors: Rolland, Yves | van Kan, Gabor Abellan | Nourhashemi, Fati | Andrieu, Sandrine | Cantet, Christelle | Guyonnet-Gillette, Sophie | Vellas, Bruno

Article Type: Research Article

Abstract: Among elderly without cognitive impairment, poor physical performances have been reported to predict cognitive decline and dementia. Our aim was to explore the predictive value of balance impairment for cognitive decline in 686 community-dwelling Alzheimer's disease (AD) patients (REAL.FR study). Being unable to stand on one leg for five seconds or more defined balance impairment. Cognitive decline was assessed using the Mini-Mental Status Examination (MMSE) score. Co-morbidities, behavioral and psychological symptoms of dementia (BPSD) using the Neuropsychiatric Inventory score, medication, and level of education were assessed at the hospital. MMSE and balance were reported every six months during two years. …Linear mixed model analyses were performed. At baseline, participants with balance impairment (15.2% of the sample) were significantly older, had a lower MMSE score and more BPSD, co-morbidities, and medication. After adjustment for the potential covariates, the presence of balance impairment at each assessment was associated with a mean MMSE decline of 9.2 (1.4) points at two years; having no balance impairment at each assessment was associated with a mean MMSE decline of 3.8 (0.3) points at two years (p < 0.001). An abnormal one-leg balance test is a marker of more advanced dementia and predicts a higher rate of cognitive decline. Show more

Keywords: Alzheimer's disease, assessment tool, balance, cognitive decline, physical performances, risk factors in epidemiology

DOI: 10.3233/JAD-2009-0987

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 525-531, 2009