Journal of Alzheimer's Disease - Volume 24, issue 1

Authors: Zhou, Rui | Deng, Juan | Zhang, Meng | Zhou, Hua-Dong | Wang, Yan-Jiang

Article Type: Research Article

Abstract: Alzheimer's disease (AD) and osteoporosis are common chronic degenerative disorders which are strongly associated with advanced age. Some studies suggest that low bone mineral density (BMD) is related to the increased risk of AD. We conducted a 5-year prospective study to exam the association between BMD and the risk of AD in a cohort of Chinese elderly people. Of 3263 community residents aged 65 years and over, 2019 were enrolled into the study and followed up annually for 5 years. At baseline demographic data, smoking and drinking status, medical history, cognitive status, and blood samples were collected. BMD was measured …by dual energy X-ray absorptiometry (DEXA) scanning at baseline and during follow-up. Cox proportional hazards analysis was used to evaluate the association with BMD and incidence of AD. Over the follow-up of 5 years, AD developed in 132 subjects. Baseline BMD, bone loss rate, current smoking, and daily drinking were associated with increased risk of AD, while higher baseline plasma leptin level was associated with decreased risk of AD, in both women and men. Low BMD and increased loss rate of BMD were associated with higher risk of AD. Cigarette smoking, alcohol drinking, and lower leptin level are risk factors for AD. Uncovering the relation linking osteoporosis and AD is important for understanding the pathogenesis and developing therapeutic strategies for these two common disorders afflicting elderly people. Show more

Keywords: Alzheimer's disease, bone loss, bone mineral density, leptin

DOI: 10.3233/JAD-2010-101467

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 101-108, 2011

Authors: Keller, Connor | Kadir, Ahmadul | Forsberg, Anton | Porras, Omar | Nordberg, Agneta

Article Type: Research Article

Abstract: The effects of galantamine (16 to 24 mg/day) treatment on brain functional activities (blood flow and glucose metabolism) were examined in 18 patients with mild Alzheimer's disease (AD) in relation to brain acetylcholinesterase (AChE) activity and nicotinic receptors and cognitive function. The study consisted of an initial double-blind phase of three months (short-term) followed by an open-label phase until twelve months after the beginning of the study (long-term). The AD patients underwent positron emission tomography (PET) studies with the tracers [15 O]-H2 O for measurement of regional cerebral blood flow (rCBF) at baseline, 3 weeks, 3 and 12 months treatment, …and [18 F]-fluoro-deoxyglucose (FDG) for measurement of regional cerebral metabolic rate for glucose (rCMRglc) at baseline and 12 months. A battery of neuropsychological assessments was performed on each patient in order to follow changes in cognition during the treatment period. Throughout the study, different cortical areas showed significant increases in rCBF after galantamine treatment. rCBF positively correlated with AChE activity, nicotinic receptors and cognition. In addition to these positive changes, an increase in rCMRglc in the frontal brain region and stabilization in other cortical areas was observed after 12 months galantamine treatment. This stabilization in rCMRglc was also correlated with a stabilization of cognition. Our results ultimately suggest that treatment with galantamine has a long-term positive effect on brain perfusion and rCMRglc and stabilizes cognition. Show more

Keywords: Alzheimer's disease, cerebral blood flow, cerebral glucose metabolism, cognition, galantamine, positron emission tomography

DOI: 10.3233/JAD-2010-101290

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 109-123, 2011

Authors: Chamberlain, Samuel R. | Blackwell, Andrew D. | Nathan, Pradeep J. | Hammond, Geoff | Robbins, Trevor W. | Hodges, John R. | Michael, Albert | Semple, James M. | Bullmore, Edward T. | Sahakian, Barbara J.

Article Type: Research Article

Abstract: The ability to predict cognitive deterioration in patients with dementia holds valuable potential for clinical trials and early intervention. This study identified cognitive domains deteriorating differentially over time as well as baseline predictors of subsequent cognitive decline in patients referred to a memory clinic. Twenty-six subjects with Alzheimer's disease (AD) and 43 subjects with Subjective Memory Impairment (SMI) were entered into a longitudinal study in which cognitive function was assessed at baseline and at 8-monthly intervals for 2 years, using a range of well-validated measures. Thirty-seven patients with depression and 39 healthy controls were also longitudinally assessed. AD was associated …with disproportionate deterioration over time on general measures of cognitive function, multiple measures of mnemonic processing, mental fluency (letter and category), and aspects of motor speed. SMI showed restricted relative cognitive deterioration on general measures of cognitive function, on a subset of memory measures, and on letter but not category fluency. Secondary analysis showed that earliest detectable ADAS-cog and MMSE decline in AD was at 16 months, while several specific neuropsychological indices were sensitive as early as 8 months (graded naming test, semantic naming, and the category/letter fluency tests). In combination, baseline/early changes in cognitive performance, alongside clinical measures, predicted 48% of disease progression over two years in memory impaired patients as a whole. These findings have implications for identifying patients likely to benefit from disease modifying agents, and for designing, powering, enriching, and implementing future clinical trials. Follow-up studies in independent populations are needed to validate predictive algorithms identified. Show more

Keywords: Alzheimer's disease, cognition, dementia, enrichment, longitudinal, prediction, semantic

DOI: 10.3233/JAD-2010-100450

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 125-136, 2011

Authors: Schrag, Matthew | Crofton, Andrew | Zabel, Matthew | Jiffry, Arshad | Kirsch, David | Dickson, April | Mao, Xiao Wen | Vinters, Harry V. | Domaille, Dylan W. | Chang, Christopher J. | Kirsch, Wolff

Article Type: Research Article

Abstract: Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI-detectable microbleeds in many of these patients. It is possible that CAA-related microbleeding is a source of pathological iron in the AD brain. Because the homeostasis of copper, iron, and zinc are so intimately linked, we determined whether CAA contributes to changes in the brain levels of these metals. We obtained brain tissue from AD patients with severe CAA to compare to AD patients without evidence of vascular amyloid-β. Patients with severe CAA had significantly higher non-heme …iron levels. Histologically, iron was deposited in the walls of large CAA-affected vessels. Zinc levels were significantly elevated in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD tissues and copper was found to be prominently deposited on the vasculature in CAA. Together, these findings demonstrate that CAA is a significant variable affecting transition metals in AD. Show more

Keywords: Atomic absorption, coppersensor 1 (CS1), ferrous, non-heme iron

DOI: 10.3233/JAD-2010-101503

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 137-149, 2011

Authors: Tales, Andrea | Bayer, Antony J. | Haworth, Judy | Snowden, Robert J. | Philips, Michelle | Wilcock, Gordon

Article Type: Research Article

Abstract: In the study of Alzheimer's disease, a multidisciplinary research approach has identified significant abnormality in several areas of visual and visual attention-related brain function in addition to those typically measured as part of clinical diagnosis. This raises the possibility that a similar approach applied to amnestic mild cognitive impairment (aMCI) will increase our understanding of its theoretical and clinical constructs, particularly if functions whose integrity is heterogeneous with respect to etiological outcome can be found. In this study we examined visual search performance (the brain's ability to search effectively throughout the environment for a particular object) in aMCI compared to …healthy aging. Cross-sectionally, visual search performance in aMCI was significantly poorer than in healthy aging, with greater intra-group performance heterogeneity in the aMCI compared to the healthy older adult group. This outcome illustrates that although individuals within an aMCI group ostensibly have the same condition they can differ substantially with respect to the integrity of aspects of brain function. Such findings may have implications for the clinical management of the individual patient. The results from the longitudinal aspect of this study also illustrate how heterogeneity in the performance of brain operations other than memory in aMCI may help to inform the likelihood of their developing dementia, as those patients who were diagnosed with dementia within 2.5 years of baseline measurement showed significantly poorer visual search performance compared to those who did not. Show more

Keywords: Alzheimer's disease, attention, dementia, mild cognitive impairment, reaction time, visual search

DOI: 10.3233/JAD-2010-101818

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 151-160, 2011

Authors: Ramirez, Carlos | Tercero, Inmaculada | Pineda, Antonia | Burgos, Javier S.

Article Type: Research Article

Abstract: Statins have recently been shown to act as protectants against several neuropathological conditions. They have received special attention in the field of Alzheimer's disease (AD), where epidemiological studies indicating a lower prevalence of AD/dementia in statin-prescribed populations. Excitotoxicity, which derives from the overstimulation of glutamate receptors, is a major cause of neuron death in several neurological diseases, including AD and epilepsy. We have carried out a comparative study to investigate the effects of all the commercially available statins (simvastatin, lovastatin, fluvastatin, pravastatin, and atorvastatin) on neuron damage and memory impairment. To this end, we studied neurodegeneration in a mouse model …by systemic administration of kainate. Simvastatin was the most effective statin in reducing the deleterious effects caused by kainate, including the severity of seizures, excitotoxicity, oxidative damage, neuritic dystrophy and apoptosis in the hippocampus and other limbic structures of the brain cortex. Lovastatin was the second most efficient statin in preventing seizures and histopathological signs of excitotoxicity, whilst fluvastatin, pravastatin, and atorvastatin showed neither antiepileptic nor neuroprotective effects. Only simvastatin enhanced episodic-like memory. To the best of our knowledge this is the first in vivo study to analyze the neuroprotective effect of all the commercially available statins. Our results suggest that both simvastatin and lovastatin (but especially simvastatin) may well have therapeutic potential in the treatment of neurodegenerative diseases involving excitotoxicity and memory impairment, including AD. Show more

Keywords: Alzheimer's disease, apoptosis, excitotoxicity, HMG-CoA reductase inhibitors, kainate, memory impairment, oxidative damage, seizure, statins

DOI: 10.3233/JAD-2010-101653

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 161-174, 2011

Authors: Bucossi, Serena | Ventriglia, Mariacarla | Panetta, Valentina | Salustri, Carlo | Pasqualetti, Patrizio | Mariani, Stefania | Siotto, Mariacristina | Rossini, Paolo Maria | Squitti, Rosanna

Article Type: Research Article

Abstract: There is an ongoing debate on the involvement of systemic copper (Cu) dysfunctions in Alzheimer's disease (AD), and clinical studies comparing Cu levels in serum, plasma, and cerebrospinal fluid (CSF) of AD patients with those of healthy controls have delivered non-univocal and often conflicting results. In an attempt to evaluate whether Cu should be considered a potential marker of AD, we applied meta-analysis to a selection of 26 studies published in the literature. Meta-analysis is a quantitative method that combines the results of independent reports to distinguish between small effects and no effects, random variations, variations in sample used, or …in different analytical approaches. The subjects' sample obtained by merging studies was a pooled total of 761 AD subjects and 664 controls for serum Cu studies, 205 AD subjects and 167 controls for plasma Cu, and of 116 AD subjects and 129 controls for CSF Cu. Our meta-analysis of serum data showed that AD patients have higher levels of serum Cu than healthy controls. Plasma data did not allow conclusions, due to their high heterogeneity, but the meta-analysis of the combined serum and plasma studies confirmed higher Cu levels in AD. The analysis of CSF data, instead, revealed no difference between AD patients and controls. Show more

Keywords: Alzheimer's disease, cerebrospinal fluid, copper, meta-analysis, plasma, serum

DOI: 10.3233/JAD-2010-101473

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 175-185, 2011

Authors: Purohit, Dushyant P. | Batheja, Nirmala O. | Sano, Mary | Jashnani, Kusum D. | Kalaria, Rajesh N. | Karunamurthy, Arivarasan | Kaur, Shalinder | Shenoy, Asha S. | Van Dyk, Kathleen | Schmeidler, James | Perl, Daniel P.

Article Type: Research Article

Abstract: Systematic studies on Alzheimer's disease (AD)-related pathology that complement clinical and epidemiological data on dementia from low and middle income countries are rare. We report the first large study on AD-related pathology in autopsy service-derived brains from an urban center in India, a low/middle income country, and compare findings with a similar sample from New York. Amyloid-β plaques and neurofibrillary tangles were assessed in 91 brain specimens derived from hospital autopsy cases from Mumbai, India (age 60+ years; mean age 71.1 years, ±8.3 SD; range 60–107 years) and compared with identically examined age-matched sample obtained in New York. These cases …had no known clinical history of dementia. Our study showed that in comparison with the New York sample, the mean brain weight of the Mumbai sample was lower (p = 0.013) and mean diffuse plaque density was higher (p = 0.019), while differences in mean density and counts of neurofibrillary tangles and neuritic plaques were not statistically significant (p > 0.05). Our findings indicate that the burden of AD-related pathology was approximately equivalent in Mumbai and New York samples, which is at variance with expected lower AD-related lesion burden based on the clinical/epidemiological studies suggesting lower prevalence of AD in India. Show more

Keywords: AD-related pathology, Alzheimer's disease, amyloid-β plaques, developing countries, LMIC, neurofibrillary tangles, senile plaques

DOI: 10.3233/JAD-2010-101698

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 187-196, 2011

Article Type: Other

DOI: 10.3233/JAD-2010-101699

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 197-199, 2011