NIH PubMed latest 50 research articles on Alzheimer's

Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer's disease.

Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer's disease.

Eur Radiol. 2009 Jul 9;

Authors: Yoshiura T, Hiwatashi A, Noguchi T, Yamashita K, Ohyagi Y, Monji A, Nagao E, Kamano H, Togao O, Honda H

The purpose of this study was to determine whether arterial spin labelling (ASL) at 3-T MR imaging can be used to discriminate individuals with Alzheimer's disease (AD) from cognitively normal subjects. Twenty AD patients and 23 cognitively normal control subjects were studied using ASL on a 3-T MR imager. Absolute regional cerebral blood flow (rCBF) maps were calculated. In addition, normalized rCBF maps were obtained using CBF in the sensorimotor cortex for normalization. A voxel-wise comparison of these rCBF maps between the AD and control groups was performed using the two-sample t test. Individuals with AD were discriminated from control subjects based on mean rCBF values within a region-of-interest defined by the t test, and the discriminating performance was evaluated by the receiver operating characteristic (ROC) analysis. Comparisons of both absolute and normalized rCBF maps revealed areas of significant hypoperfusion caused by the effects of AD in the bilateral precunei and posterior cingulate gyri. ROC analyses resulted in area under the curve (AUC) values of 0.861 to 0.877 for absolute and 0.910 to 0.932 for normalized rCBF. Our results suggest that ASL at 3-T MR imaging can be used to help discriminate individuals with AD from normal subjects.

PMID: 19588145 [PubMed - as supplied by publisher]

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease.

Kim SR, Choi SH, Ha CK, Park SG, Pyun HW, Yoon DH

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease.

J Clin Neurol. 2009 Jun;5(2):85-90

Authors: Kim SR, Choi SH, Ha CK, Park SG, Pyun HW, Yoon DH

BACKGROUND AND PURPOSE: Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer's disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients. METHODS: Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2+/-8.8 years, mean+/-SD, n=36) and those with moderate-to-severe WMC (74.6+/-4.6 years, n=36) on brain MRI. RESULTS: In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels >/=12.9 micromol/L - with the bottom tertile - tHcy levels </=9.4 micromol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA. CONCLUSIONS: Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.

PMID: 19587815 [PubMed - in process]

Dysfunctions of neuronal and glial intermediate filaments in disease.

Liem RK, Messing A

Dysfunctions of neuronal and glial intermediate filaments in disease.

J Clin Invest. 2009 Jul;119(7):1814-24

Authors: Liem RK, Messing A

Intermediate filaments (IFs) are abundant structures found in most eukaryotic cells, including those in the nervous system. In the CNS, the primary components of neuronal IFs are alpha-internexin and the neurofilament triplet proteins. In the peripheral nervous system, a fifth neuronal IF protein known as peripherin is also present. IFs in astrocytes are primarily composed of glial fibrillary acidic protein (GFAP), although vimentin is also expressed in immature astrocytes and some mature astrocytes. In this Review, we focus on the IFs of glial cells (primarily GFAP) and neurons as well as their relationship to different neurodegenerative diseases.

PMID: 19587456 [PubMed - in process]

The Nun Study. Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

Iacono D, Markesbery WR, Gross M, Pletnikova O, Rudow G, Zandi P, Troncoso JC

The Nun Study. Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

Neurology. 2009 Jul 8;

Authors: Iacono D, Markesbery WR, Gross M, Pletnikova O, Rudow G, Zandi P, Troncoso JC

BACKGROUND: It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. METHODS: Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. RESULTS: A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. CONCLUSIONS: 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.

PMID: 19587326 [PubMed - as supplied by publisher]

Conversion of amyloid positive and negative MCI to AD over 3 years. An 11C-PIB PET study.

Conversion of amyloid positive and negative MCI to AD over 3 years. An 11C-PIB PET study.

Neurology. 2009 Jul 8;

Authors: Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Någren K, Bullock R, Walker Z, Kennedy A, Fox NC, Rossor MN, Rinne JO, Brooks DJ

BACKGROUND: Patients with amnestic mild cognitive impairment (MCI) represent an important clinical group as they are at increased risk of developing Alzheimer disease (AD). (11)C-PIB PET is an in vivo marker of brain amyloid load. OBJECTIVE: To assess the rates of conversion of MCI to AD during a 3-year follow-up period and to compare levels of amyloid deposition between MCI converters and nonconverters. METHODS: Thirty-one subjects with MCI with baseline (11)C-PIB PET, MRI, and neuropsychometry have been clinically followed up for 1 to 3 years (2.68 +/- 0.6 years). Raised cortical (11)C-PIB binding in subjects with MCI was detected with region of interest analysis and statistical parametric mapping. RESULTS: Seventeen of 31 (55%) subjects with MCI had increased (11)C-PIB retention at baseline and 14 of these 17 (82%) clinically converted to AD during follow-up. Only one of the 14 PIB-negative MCI cases converted to AD. Of the PIB-positive subjects with MCI, half (47%) converted to AD within 1 year of baseline PIB PET, these faster converters having higher tracer-retention values than slower converters in the anterior cingulate (p = 0.027) and frontal cortex (p = 0.031). Seven of 17 (41%) subjects with MCI with known APOE status were epsilon4 allele carriers, this genotype being associated with faster conversion rates in PIB-positive subjects with MCI (p = 0.035). CONCLUSIONS: PIB-positive subjects with mild cognitive impairment (MCI) are significantly more likely to convert to AD than PIB-negative patients, faster converters having higher PIB retention levels at baseline than slower converters. In vivo detection of amyloid deposition in MCI with PIB PET provides useful prognostic information.

PMID: 19587325 [PubMed - as supplied by publisher]

Matrix metalloprotease-9 inhibition improves amyloid {beta}-mediated cognitive impairment and neurotoxicity in mice.

Matrix metalloprotease-9 inhibition improves amyloid {beta}-mediated cognitive impairment and neurotoxicity in mice.

J Pharmacol Exp Ther. 2009 Jul 8;

Authors: Mizoguchi H, Takuma K, Fukuzaki E, Ibi D, Someya E, Akazawa KH, Alkam T, Tsunekawa H, Mouri A, Noda Y, Nabeshima T, Yamada K

In Alzheimer's disease (AD), the expression of matrix metalloproteases (MMPs), which are capable of degrading extracellular matrix proteins, is increased in the brain. Previous studies with cultured glial cells have demonstrated that amyloid beta (Abeta) protein can induce the expression of MMPs, which could be involved in the degradation of Abeta. In the present study, we investigated the role of MMP-2 and MMP-9 in cognitive impairment induced by the injection of Abeta in mice. The i.c.v. injection of Abeta25-35, Abeta1-40 and Abeta1-42, but not Abeta40-1, transiently increased MMP-9, but not MMP-2, activity and protein expression in the hippocampus. Immunohistochemistry revealed the expression of MMP-9 to be increased in both neurons and glial cells in the hippocampus after Abeta treatment. The Abeta-induced cognitive impairment in vivo as well as neurotoxicity in vitro was significantly alleviated in MMP-9 homozygous knockout mice and by treatment with MMP inhibitors. These results suggest the increase in MMP-9 expression in the hippocampus to be involved in the development of cognitive impairment induced by Abeta1-40. Thus, specific inhibitors of MMP-9 may have therapeutic potential for the treatment of AD. Our findings suggest that, as opposed to expectations based on previous findings, MMP-9 plays a causal role in Abeta-induced cognitive impairment and neurotoxicity.

PMID: 19587312 [PubMed - as supplied by publisher]

Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein.

Xu D, Sharma C, Hemler ME

Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein.

FASEB J. 2009 Jul 8;

Authors: Xu D, Sharma C, Hemler ME

Using mass spectrometry, we identified ADAM10 (a membrane-associated metalloproteinase) as a partner for TSPAN12, a tetraspanin protein. TSPAN12-ADAM10 interaction was confirmed by reciprocal coimmunoprecipitation in multiple tumor cell lines. TSPAN12, to a greater extent than other tetraspanins (CD81, CD151, CD9, and CD82), associated with ADAM10 but not with ADAM17. Overexpression of TSPAN12 enhanced ADAM10-dependent shedding of amyloid precursor protein (APP) in MCF7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. Conversely, siRNA ablation of endogenous TSPAN12 markedly diminished APP proteolysis in both cell lines. Furthermore, TSPAN12 overexpression enhanced ADAM10 prodomain maturation, whereas TSPAN12 ablation diminished ADAM10 maturation. A palmitoylation-deficient TSPAN12 mutant failed to associate with ADAM10, inhibited ADAM10-dependent proteolysis of APP, and inhibited ADAM10 maturation, most likely by interfering with endogenous wild-type TSPAN12. In conclusion, TSPAN12 serves as a novel and robust partner for ADAM10 and promotes ADAM10 maturation, thereby facilitating ADAM10-dependent proteolysis of APP. This novel mode of regulating APP cleavage is of relevance to Alzheimer's disease therapy.-Xu, D., Sharma, C., Hemler, M. E. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein.

PMID: 19587294 [PubMed - as supplied by publisher]

Deletion of the alpha7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease.

Dziewczapolski G, Glogowski CM, Masliah E, Heinemann SF

Deletion of the alpha7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease.

J Neurosci. 2009 Jul 8;29(27):8805-15

Authors: Dziewczapolski G, Glogowski CM, Masliah E, Heinemann SF

It has been recently shown that the Alzheimer's disease (AD) pathogenic peptide amyloid beta(1-42) (Abeta(1-42)) binds to the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) with high affinity and the alpha7nAChR and Abeta(1-42) are both found colocalized in neuritic plaques of human brains with AD. Moreover, the intraneuronal accumulation of Abeta(1-42) was shown to be facilitated by its high-affinity binding to the alpha7nAChR, and alpha7nAChR activation mediates Abeta-induced tau protein phosphorylation. To test the hypothesis that alpha7nAChRs are involved in AD pathogenesis, we used a transgenic mouse model of AD overexpressing a mutated form of the human amyloid precursor protein (APP) and lacking the alpha7nAChR gene (APPalpha7KO). We have shown that, despite the presence of high amounts of APP and amyloid deposits, deleting the alpha7nAChR subunit in the mouse model of AD leads to a protection from the dysfunction in synaptic integrity (pathology and plasticity) and learning and memory behavior. Specifically, APPalpha7KO mice express APP and Abeta at levels similar to APP mice, and yet they were able to solve a cognitive challenge such as the Morris water maze test significantly better than APP, with performances comparable to control groups. Moreover, deleting the alpha7nAChR subunit protected the brain from loss of the synaptic markers synaptophysin and MAP2, reduced the gliosis, and preserved the capacity to elicit long-term potentiation otherwise deficient in APP mice. These results are consistent with the hypothesis that the alpha7nAChR plays a role in AD and suggest that interrupting alpha7nAChR function could be beneficial in the treatment of AD.

PMID: 19587288 [PubMed - in process]

Minute effects of sex on the aging brain: a multisample magnetic resonance imaging study of healthy aging and Alzheimer's disease.

Minute effects of sex on the aging brain: a multisample magnetic resonance imaging study of healthy aging and Alzheimer's disease.

J Neurosci. 2009 Jul 8;29(27):8774-83

Authors: Fjell AM, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Walhovd KB

Age is associated with substantial macrostructural brain changes. While some recent magnetic resonance imaging studies have reported larger age effects in men than women, others find no sex differences. As brain morphometry is a potentially important tool in diagnosis and monitoring of age-related neurological diseases, e.g., Alzheimer's disease (AD), it is important to know whether sex influences brain aging. We analyzed cross-sectional magnetic resonance scans from 1143 healthy participants from seven subsamples provided by four independent research groups. In addition, 96 patients with mild AD were included. Estimates of cortical thickness continuously across the brain surface, as well as volume of 17 subcortical structures, were obtained by use of automated segmentation tools (FreeSurfer). In the healthy participants, no differences in aging slopes between women and men were found in any part of the cortex. Pallidum corrected for intracranial volume showed slightly higher age correlations for men. The analyses were repeated in each of the seven subsamples, and the lack of age x sex interactions was largely replicated. Analyses of the AD sample showed no interactions between sex and age for any brain region. We conclude that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.

PMID: 19587284 [PubMed - in process]

Impact of the most frequent chronic health conditions on the quality of life among people aged >15 years in Madrid.

Peña ME, García RJ, Olalla JM, Llanos EV, de Miguel AG, Cordero XF

Impact of the most frequent chronic health conditions on the quality of life among people aged >15 years in Madrid.

Eur J Public Health. 2009 Jul 8;

Authors: Peña ME, García RJ, Olalla JM, Llanos EV, de Miguel AG, Cordero XF

BACKGROUND: This study sought to ascertain to what degree health-related quality of life (HRQL) in the City of Madrid was affected by each of the most frequent chronic health conditions, and the specific quality-of-life (QL) domains on which such health conditions had the greatest impact, taking co-morbidity and socio-demographic variables into account. METHODS: A descriptive, analytical, cross-sectional study was conducted covering 7341 subjects aged >/=16 years in the City of Madrid. Data were collected on self-reported diagnosed morbidity, including hypertension, hypercholesterolaemia, varicose veins, diabetes, chronic asthma/bronchitis, myocardial infarction/angina pectoris, stomach problems, allergy, arthrosis/arthritis or rheumatism, depression/anxiety, cataracts, cerebrovascular accidents (CVACs), chronic constipation, osteoporosis and Alzheimer's disease or dementia. HRQL was measured using the COOP/WONCA questionnaire. The effects of diagnosis, age, social class, gender and the co-morbidity were analysed using a multivariate analysis of covariance (ANCOVA). RESULTS: The chronic health conditions that registered the worst overall mean scores on the COOP/WONCA questionnaire were Alzheimer's disease or dementia, Parkinson's disease, fibromyalgia, CVACs and depression, with scores of over 26 points in all cases. After the introduction of socio-demographic variables in the model, the highest values of Snedecor's F-test corresponds to depression (F = 461.63), 'arthrosis/arthritis or rheumatism' (F = 175.41), Alzheimer's disease or dementia (F = 65.70), gastric disorders (F = 65.17), cancer (F = 43.08) and CVACs (F = 41.65). CONCLUSIONS: Depression and 'arthrosis/arthritis or rheumatism' are the two chronic health conditions, which have the greatest impact on HRQL in Madrid's citizens, therefore is mandatory to propose and implement public health strategies that would reduce the prevalence and morbidity of such disorders.

PMID: 19587225 [PubMed - as supplied by publisher]

Behavioral phenotyping of a murine model of Alzheimer's disease in a seminaturalistic environment using RFID tracking.

Lewejohann L, Hoppmann AM, Kegel P, Kritzler M, Krüger A, Sachser N

Behavioral phenotyping of a murine model of Alzheimer's disease in a seminaturalistic environment using RFID tracking.

Behav Res Methods. 2009 Aug;41(3):850-6

Authors: Lewejohann L, Hoppmann AM, Kegel P, Kritzler M, Krüger A, Sachser N

Neurodegenerative disorders such as Alzheimer's disease (AD) are increasingly threatening public health. Most animal models of AD consist of transgenic mice that are usually housed singly or in unisexual groups in small barren cages. Such restricted environments, however, prevent the mice from showing a variety of species-specific behaviors and consequently may constrain comprehensive behavioral phenotyping. On the other hand, allowing the animals to freely organize their lives in a spacious physically and socially enriched environment makes behavioral phenotyping laborious and time consuming. Radio frequency identification (RFID) using a network of antennae and small glass-coated transponders labeling each individual allows for gathering spatiotemporal information about a large number of individuals in parallel. The aim of this project was to use the RFID technique to facilitate the characterization of mice carrying a genetic disposition to develop AD-like pathology and of their wild-type conspecifics in a spacious seminaturalistic environment.

PMID: 19587201 [PubMed - in process]

The Contribution of Executive Control on Verbal-Learning Impairment in Patients with Parkinson's Disease with Dementia and Alzheimer's Disease.

O'Brien TJ, Wadley V, Nicholas AP, Stover NP, Watts R, Griffith HR

The Contribution of Executive Control on Verbal-Learning Impairment in Patients with Parkinson's Disease with Dementia and Alzheimer's Disease.

Arch Clin Neuropsychol. 2009 Jul 8;

Authors: O'Brien TJ, Wadley V, Nicholas AP, Stover NP, Watts R, Griffith HR

Deficits in learning, memory, and executive functions are common cognitive sequelae of Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD); however, the pattern of deficits within these populations is distinct. Hierarchical regression was used to investigate the contribution of two measures with executive function properties (Verbal Fluency and CLOX) on list-learning performance (CVLT-II total words learned) in a sample of 25 PDD patients and 25 matched AD patients. Executive measures were predictive of list learning in the PDD group after the contribution of overall cognition and contextual verbal learning was accounted for, whereas in the AD group the addition of executive measures did not add to prediction of variance in CVLT-II learning. These findings suggest that deficits in executive functions play a vital role in learning impairments in patients with PDD; however, for AD patients, learning difficulties appear relatively independent of executive dysfunction.

PMID: 19587066 [PubMed - as supplied by publisher]

Polymorphisms of the estrogen receptor alpha (ESR1) gene and the risk of Alzheimer's disease in a southern Chinese community.

Ma SL, Tang NL, Tam CW, Lui VW, Lau ES, Zhang YP, Chiu HF, Lam LC

Polymorphisms of the estrogen receptor alpha (ESR1) gene and the risk of Alzheimer's disease in a southern Chinese community.

Int Psychogeriatr. 2009 Jul 9;:1-10

Authors: Ma SL, Tang NL, Tam CW, Lui VW, Lau ES, Zhang YP, Chiu HF, Lam LC

ABSTRACTBackground: Alzheimer's disease (AD) is a neurodegenerative disease with a higher prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been identified throughout the brain. Owing to the putative neuroprotective effects of estrogen, estrogen receptor gene is a potential candidate modulating the development of AD. Preliminary associations between two polymorphisms of ESR1 (PvuII and XbaI) gene and AD have been reported.Methods: In this study, 16 single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database) were investigated to further evaluate the association between ESR1 polymorphisms and the risk of AD in the Chinese population.Results: A total of 233 Chinese AD patients and 245 age-matched elderly control subjects were recruited. Genetic associations were analyzed by chi-square test and interaction effect was analysed by logistic regression analysis. Five SNPs (clustered between intron 3 and intron 7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035); another two SNPs (located on exon 2 and intron 2) were shown to modulate the age-at-onset (AAO) in AD (p-value = 0.036 and 0.011).Conclusions: ESR1 gene polymorphisms may be associated with the AAO in AD. The present results provided information for possible associations between certain polymorphisms of ESR1 gene and the risk of AD.

PMID: 19586561 [PubMed - as supplied by publisher]

Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons.

Trushina E, Rana S, McMurray CT, Hua DH

Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons.

BMC Neurosci. 2009 Jul 8;10(1):73

Authors: Trushina E, Rana S, McMurray CT, Hua DH

ABSTRACT: BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion mutation in the coding region of a novel gene. The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt) contributes to the pathology. However, recent studies have identified early cellular dysfunctions that preclude aggregate formation. Suppression of aggregation is accepted as one of the markers of successful therapeutic approaches. Previously, we demonstrated that tricyclic pyrone (TP) compounds efficiently inhibited formation of amyloid-beta (Abeta) aggregates in cell and mouse models representing Alzheimer's Disease (AD). In the present study, we aimed to determine whether TP compounds could prevent aggregation and restore early cellular defects in primary embryonic striatal neurons from animal model representing HD. RESULTS: TP compounds effectively inhibit aggregation caused by mhtt in neurons and glial cells. Treatment with TP compounds also alleviated cholesterol accumulation and restored clathrin-independent endocytosis in HD neurons. CONCLUSIONS: We have found that TP compounds not only blocked mhtt-induced aggregation, but also alleviated early cellular dysfunctions that preclude aggregate formation. Our data suggest TP molecules may be used as lead compounds for prevention or treatment of multiple neurodegenerative diseases including HD and AD.

PMID: 19586540 [PubMed - as supplied by publisher]

Cognitive functioning in Alzheimer's and vascular dementia: A meta-analysis.

Mathias JL, Burke J

Cognitive functioning in Alzheimer's and vascular dementia: A meta-analysis.

Neuropsychology. 2009 Jul;23(4):411-23

Authors: Mathias JL, Burke J

Differentiating between Alzheimer's disease (AD) and vascular dementia (VaD) remains difficult but important if existing pharmacological treatments are to provide symptomatic relief in the case of AD or to alter disease progression in the case of VaD. Cognitive assessments play an important role in aiding diagnosis, despite a lack of clear evidence defining the cognitive abilities and tests that best distinguish between the two types of dementia. The current study therefore completed a meta-analysis of research comparing the cognitive abilities of persons diagnosed with AD and VaD. A comprehensive search was undertaken of the PubMed and PsychInfo databases, with 81 studies being eligible for inclusion. Weighted Cohen's d effect sizes, percentage overlap statistics, fail-safe Ns, and confidence intervals were calculated for all cognitive tests. Of the tests that were examined by more than one study, there was one test of perception and one test of verbal memory that showed large and significant group differences. There were an additional 12 tests that may prove useful. However, all cognitive tests were limited in their ability to discriminate between AD and VaD, suggesting that they should be used cautiously and only in conjunction with other information (imaging, medical history) when diagnosing patients. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID: 19586206 [PubMed - in process]

The cost of dementia in europe: a review of the evidence, and methodological considerations.

Jönsson L, Wimo A

The cost of dementia in europe: a review of the evidence, and methodological considerations.

Pharmacoeconomics. 2009;27(5):391-403

Authors: Jönsson L, Wimo A

Alzheimer's disease (AD) is a leading cause of disability in the elderly, leading to a high burden on caregivers and costs to society. This article describes the current level of data availability regarding the costs of AD in Europe, summarizes and compares findings from previous studies in different countries, and discusses the applicability of available data for modelling purposes. A literature review was conducted for papers in any language reporting data on costs of care for patients with diagnosed dementia or possible/probable AD. Only papers reporting patient-level data on costs were included. A total of 16 studies were identified: from the Nordic region (4), the UK (3), Spain (3), France (2), Italy (2), Belgium (1) and Germany (1). There is large variation in total cost estimates, depending on, for example, differences in study methodology, setting, type and severity of patients included, range of costs assessed and the choice of principle for valuing informal care. The median value for total annual care costs in all studies was &euro28 000 (range &euro6614-&euro64 426) [year 2005 values]. Few studies assessed aspects of disease severity other than cognitive function. The costs of AD in Europe are substantial and increase with disease severity. Methodological differences between studies make comparison across countries and healthcare systems difficult, and there is a need to standardize methods for assessing and valuing informal care. Patient-level information on resource use is required to analyse determinants of care costs and predict the impact of therapeutic interventions. More data are needed to support future economic evaluations of therapies for AD.

PMID: 19586077 [PubMed - in process]

Is dementia preventable?

Korczyn AD

Is dementia preventable?

Dialogues Clin Neurosci. 2009;11(2):213-6

Authors: Korczyn AD

Dementia is an important public health problem of increasing magnitude. At present, available therapies provide only minor and temporary relief, and attempts to find a cure have so far failed. Epidemiological studies have identified risk factors for dementia, particularly Alzheimer's disease and vascular dementia. In principle, these findings provide an opportunity to intervene and prevent the dementia epidemic. Attention to nongenetic risk factors such as hypertension, hyperlipidemia, smoking, and obesity may thus not only prevent cardiovascular disease but also dementia, although it is difficult to prove the efficacy of these measures for dementia prevention.

PMID: 19585956 [PubMed - in process]

The effects of cardiovascular risk factors on cognitive compromise.

Beeri MS, Ravona-Springer R, Silverman JM, Haroutunian V

The effects of cardiovascular risk factors on cognitive compromise.

Dialogues Clin Neurosci. 2009;11(2):201-12

Authors: Beeri MS, Ravona-Springer R, Silverman JM, Haroutunian V

As life expectancy in the United States continues to increase, the projected numbers of elderly people who will develop dementia will grow rapidly. This paper reviews four well-established cardiovascular risk factors (type 2 diabetes, hypertension, cholesterol, and inflammation), for which there is longitudinal epidemiological evidence of increased risk of dementia, Alzheimer's disease, mild cognitive impairment, and cognitive decline. These risk factors are of special interest because of their potential modifiability, which may affect the course of cognitive compromise. Diabetes is the cardiovascular risk factor (CvRF) most consistently associated with cognition. Hypertension in midlife is consistently associated with cognition, but its associations with late-life hypertension are less clear. Total cholesterol is not consistently associated with cognition. Interleukin-6 and C-reactive protein are inflammatory markers relatively consistently associated with cognition. Composites of the CvRFs increase the risk for dementia in a dose-dependent fashion, suggesting a cumulative effect of these factors on neuronal stress. In the relatively few studies that have reported interactions of risk factors, they potentiate each other. The effect of each of these risk factors varies according to apolipoprotein E genotype. It may be that the effect of these risk factors varies according to the presence of the others, and these complex relationships underlie the biological mechanisms of cognitive compromise. This may be crucial for understanding the effects on cognition of drugs and other approaches, such as lifestyle change, for treating these risk factors.

PMID: 19585955 [PubMed - in process]

Imaging in Alzheimer's disease.

Scheltens P

Imaging in Alzheimer's disease.

Dialogues Clin Neurosci. 2009;11(2):191-9

Authors: Scheltens P

Neuroimaging in the early differential diagnosis of dementia has gained considerable interest over the last decade. From being used for exclusive purposes only, neuroimaging is now in the forefront of aiding in the diagnosis of Alzheimer's disease (AD), frontotemporal dementia, vascular dementia, and and dementia with Lewy bodies (DLB). With the exception of dopamine transporter single photon-emission computed tomography imaging in DLB, imaging has not yet been incorporated into the diagnostic criteria for the various dementia syndromes, but that will soon change. The recently formulated research criteria for early AD recently formulated by Dubois et al explicitly mention magnetic resonance imaging and positron emission tomography for AD, and are an example of a new diagnostic process developing. In this review, the various imaging techniques will be highlighted, with an emphasis on their ability to diagnose Alzheimer's disease and separate it from other entities.

PMID: 19585954 [PubMed - in process]

Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Brickman AM, Muraskin J, Zimmerman ME

Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Dialogues Clin Neurosci. 2009;11(2):181-90

Authors: Brickman AM, Muraskin J, Zimmerman ME

The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

PMID: 19585953 [PubMed - in process]

Is there a neuropathology difference between mild cognitive impairment and dementia?

Haroutunian V, Hoffman LB, Beeri MS

Is there a neuropathology difference between mild cognitive impairment and dementia?

Dialogues Clin Neurosci. 2009;11(2):171-9

Authors: Haroutunian V, Hoffman LB, Beeri MS

The number of studies that have investigated the neuropathology of mild cognitive impairment (MCI) is small, but growing. In this paper we have restricted our focus to the consideration of the presence and extent of postmortem findings relevant to the neuropathology of Alzheimer's disease. We have drawn from studies that have investigated the postmortem neurobiology of the brains of persons with cognitive function at the interface between unimpaired normal function and mild but definite dementia. The data derived from these studies suggest that i) the brains of persons with MCI evidence significant neuropathological and neurobiological changes relative to those without cognitive impairment; ii) in general, the neuropathological and neurobiological changes are qualitatively similar to those observed in the brains of persons with frank AD-like dementia; and iii) the neuropathological and neurobiological brain changes associated with MCI are quantitatively less than those of persons who meet criteria for dementia. Thus, the available, albeit limited, data suggests that MCI is associated with the early stages of the neurobiological and neuropathological changes that culminate in the florid lesions of AD; including the accumulation of neuritic plaques, neurofibrillary tangles, synaptic and neurotransmitter associated deficits, and significant neuronal cell death.

PMID: 19585952 [PubMed - in process]

Mechanism-based treatments for Alzheimer's disease.

Davies P, Koppel J

Mechanism-based treatments for Alzheimer's disease.

Dialogues Clin Neurosci. 2009;11(2):159-69

Authors: Davies P, Koppel J

Treatment for Alzheimer's disease is entering a new and exciting phase, with several new drugs beginning clinical trials. Many of these new therapies are based on our best current understanding of the pathogenesis of Alzheimer's disease, and are designed to try to either slow or halt the progression of the disease. There are several different theories underlying the current efforts, and these are briefly reviewed. Therapies directed against some aspect of beta-amyloid formation, against neurofibrillary tangle formation and against the inflammatory response are all considered, as are the problems associated with each area. It is as yet unclear which, if any, of these approaches will be successful, but the high level of activity in each of these three fields provides some hope that an effective treatment for Alzheimer's disease is on the horizon.

PMID: 19585951 [PubMed - in process]

Biological markers for early detection and pharmacological treatment of Alzheimer's disease.

Hampel H, Broich K, Hoessler Y, Pantel J

Biological markers for early detection and pharmacological treatment of Alzheimer's disease.

Dialogues Clin Neurosci. 2009;11(2):141-57

Authors: Hampel H, Broich K, Hoessler Y, Pantel J

The introduction of biological markers in the clinical management of Alzheimer's disease (AD) will not only improve diagnosis relating to early detection of neuropathology with underlying molecular mechanisms, but also provides tools for the assessment of objective treatment benefits. In this review, we identify a number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy of AD, and hold promise as meaningful biomarkers in the early diagnostic process, as well as for the tracking of disease-modifying pharmacological effects. These neurobiological measures appear to relate closely to pathophysiological, neuropathological, and clinical data, such as hyperphosphorylation of tau, abeta metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, and functional and cognitive decline, as well as risk of future decline. As a perspective, the important role of biomarkers in the development of innovative drug treatments for AD and the related regulatory process is discussed.

PMID: 19585950 [PubMed - in process]

Early detection of Alzheimer's disease: new diagnostic criteria.

Dubois B, Picard G, Sarazin M

Early detection of Alzheimer's disease: new diagnostic criteria.

Dialogues Clin Neurosci. 2009;11(2):135-9

Authors: Dubois B, Picard G, Sarazin M

There has been unprecedented growth of scientific knowledge about Alzheimer's disease (AD). The description of distinctive and reliable biomarkers that are now available through structural brain imaging with magnetic resonance imaging, molecular neuroimaging with positron emission tomography, and cerebrospinal fluid analyses, and a better definition of the clinical profile of amnestic disorders that occur early in the course of the disease, make it possible to identify AD with high accuracy, even in the early stages of the disease. Accordingly, new criteria for the diagnosis have been proposed that capture both the prodromal and the more advanced dementia stages of the disease in the same diagnostic framework.

PMID: 19585949 [PubMed - in process]

Novel strategies for the prevention of dementia from Alzheimer's disease.

Shineman DW, Fillit HM

Novel strategies for the prevention of dementia from Alzheimer's disease.

Dialogues Clin Neurosci. 2009;11(2):129-34

Authors: Shineman DW, Fillit HM

As the world's population continues to age, Alzheimer's disease presents a looming public health crisis that, left unchecked, threatens to overwhelm health care systems throughout the developed world. In order to significantly tackle the most catastrophic and devastating symptom of Alzheimer's disease (AD)--dementia--we must be able to detect the disease prior to the onset of clinical symptoms, and be able to offer patients preventative treatments that block or significantly slow disease progression. This review summarizes a variety of the most promising early detection methods for Alzheimer's disease (AD) and mild cognitive impairment (MCI) that could be used to identify those at high risk of developing the disease and used for monitoring disease progression and response to investigational treatments. In addition, treatment research programs that could be developed into disease-modifying treatments that significantly delay the development of dementia are highlighted. These potential treatments target many different pathways, and may one day be dosed in combination to increase efficacy and prevent cognitive deterioration in patients with AD. While we still face numerous challenges, AD researchers have made great progress in understanding disease mechanisms. As we have seen in the treatment of heart disease, even modest preventative treatments can have hugely significant clinical outcomes and drastically reduce disease prevalence on a population scale. Therefore, there is hope that the development of prophylactic treatments, combined with improved early detection methods, will provide dramatic relief for millions of aging individuals threatened by the specter of Alzheimer's disease.

PMID: 19585948 [PubMed - in process]

Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention.

Qiu C, Kivipelto M, von Strauss E

Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention.

Dialogues Clin Neurosci. 2009;11(2):111-28

Authors: Qiu C, Kivipelto M, von Strauss E

More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's disease has had tremendous impact on the affected individuals, caregivers, and society. The etiological factors, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to the potential risk roles of vascular risk factors and disorders (eg, cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders. The long-term multidomain interventions toward the optimal control of multiple vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer's disease.

PMID: 19585947 [PubMed - in process]

Alzheimer's disease and mild cognitive impairment.

Davidson M

Alzheimer's disease and mild cognitive impairment.

Dialogues Clin Neurosci. 2009;11(2):109

Authors: Davidson M

PMID: 19585946 [PubMed - in process]

Studies comparing treatment options receive a boost.

Nair P

Studies comparing treatment options receive a boost.

Nat Med. 2009 May;15(5):468

Authors: Nair P

PMID: 19424190 [PubMed - indexed for MEDLINE]

Amyloid imaging with PET: methodological issues and correlative studies.

Lucignani G

Amyloid imaging with PET: methodological issues and correlative studies.

Eur J Nucl Med Mol Imaging. 2009 Jun;36(6):1009-14

Authors: Lucignani G

PMID: 19319525 [PubMed - indexed for MEDLINE]