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‣ Immunologically Mediated Dementias

Rosenbloom, Michael H.; Smith, Sallie; Akdal, Gulden; Geschwind, Michael D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/2009 Português
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Although most dementias are due to neurodegenerative or vascular disease, it is important to diagnose immunologically mediated dementias quickly because they can be both rapidly progressive and readily treatable. They usually affect function of limbic and cortical structures, but subcortical involvement can also occur. Because of the variety of symptoms and the rapid course, these dementias present a particular challenge to the clinician and may require evaluation and intervention in the inpatient setting. Diagnostic workup typically reveals evidence of an autoimmune process and, in some cases, cancer. In contrast to the neurodegenerative processes, many of the immunologically mediated dementias respond to immunomodulatory therapy.

‣ Cognition, Language, and Clinical Pathological Features of Non-Alzheimer’s Dementias: An Overview

Reilly, Jamie; Rodriguez, Amy; Lamy, Martine; Neils-Strunjas, Jean
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, Speech-Language Pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer’s dementias: Frontotemporal Dementia, Vascular Dementia, Lewy Body Disease Dementia, and Parkinson’s Disease Dementia.

‣ Disruption of the Postsynaptic Density in Alzheimer’s Disease and Other Neurodegenerative Dementias

Gong, Yuesong; Lippa, Carol F.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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The most common causes of neurodegenerative dementia include Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). We believe that, in all 3, aggregates of pathogenic proteins are pathological substrates which are associated with a loss of synaptic function/plasticity. The synaptic plasticity relies on the normal integration of glutamate receptors at the postsynaptic density (PSD). The PSD organizes synaptic proteins to mediate the functional and structural plasticity of the excitatory synapse and to maintain synaptic homeostasis. Here, we will discuss the relevant disruption of the protein network at the PSD in these dementias and the accumulation of the pathological changes at the PSD years before clinical symptoms. We suggest that the functional and structural plasticity changes of the PSD may contribute to the loss of molecular homeostasis within the synapse (and contribute to early symptoms) in these dementias.

‣ Neuroimaging in Dementia

Tartaglia, Maria Carmela; Rosen, Howard J.; Miller, Bruce L.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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Dementia is a common illness with an incidence that is rising as the aged population increases. There are a number of neurodegenerative diseases that cause dementia, including Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia, which is subdivided into the behavioral variant, the semantic variant, and nonfluent variant. Numerous other neurodegenerative illnesses have an associated dementia, including corticobasal degeneration, Creutzfeldt–Jakob disease, Huntington’s disease, progressive supranuclear palsy, multiple system atrophy, Parkinson’s disease dementia, and amyotrophic lateral sclerosis. Vascular dementia and AIDS dementia are secondary dementias. Diagnostic criteria have relied on a constellation of symptoms, but the definite diagnosis remains a pathologic one. As treatments become available and target specific molecular abnormalities, differentiating amongst the various primary dementias early on becomes essential. The role of imaging in dementia has traditionally been directed at ruling out treatable and reversible etiologies and not to use imaging to better understand the pathophysiology of the different dementias. Different brain imaging techniques allow the examination of the structure...

‣ APOE E4 is a susceptibility factor in amnestic but not aphasic dementias

Rogalski, Emily; Rademaker, Alfred; Harrison, Theresa M; Helenowski, Irene; Johnson, Nancy; Bigio, Eileen H.; Mishra, Manjari; Weintraub, Sandra; Mesulam, M.-Marsel
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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The goal of this study was to determine if the apolipoprotein ε (ApoE) gene, which is a well-established susceptibility factor for Alzheimer’s disease (AD) pathology in typical amnestic dementias, may also represent a risk factor in the language-based dementia, primary progressive aphasia (PPA). Apolipoprotein E genotyping was obtained from 149 patients with a clinical diagnosis of PPA, 330 cognitively healthy individuals (NC) and 179 patients with a clinical diagnosis of probable Alzheimer’s disease (PrAD). Allele frequencies were compared among the groups. Analyses were also completed by gender and in two subsets of PPA patients, one where patients were classified by subtype (logopenic, agrammatic and semantic) and another where pathologic data were available. The allele frequencies for the PPA group (ε2:5%, ε3:79.5%, and ε4:15.4%) showed a distribution similar to the NC group but significantly different from the PrAD group. The presence of an ε4 allele did not influence the age of symptom onset or aid in the prediction of AD pathology in PPA. These data show that the ε4 polymorphism, which is a well-known risk factor for AD pathology in typical amnestic dementias, has no similar relationship to the clinical syndrome of PPA or its association with AD pathology.

‣ Medical Management of Frontotemporal Dementias: The Importance of the Caregiver in Symptom Assessment and Guidance of Treatment Strategies

Jicha, Gregory A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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There are no currently Food and Drug Administration-approved or proven off-label treatments for the frontotemporal dementias (FTD). Clinicians, care-givers, and patients struggle regularly to find therapeutic regimens that can alleviate the problematic behavioral and cognitive symptoms associated with these devastating conditions. Success is “hit or miss” and the lessons learned are largely anecdotal to date. Drug discovery in this area has been largely hampered by the heterogeneous clinical presentations and pathological phenotypes of disease that represent significant obstacles to progress in this area. Biologically, plausible treatment strategies include the use of antidepressants (selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor and monoamine oxidase inhibitors), acetylcholinesterase inhibitors, N-methyl-D-aspartic acid antagonists, mood stabilizers, antipsychotics, stimulants, antihypertensives, and agents that may ameliorate the symptoms of parkinsonism, pseudobulbar affect, and motor neuron disease that can often coexist with FTD. These medications all carry potential risks as well as possible benefits for the person suffering from FTD, and a clear understanding of these factors is critical in selecting an appropriate therapeutic regimen to maximize cognition and daily functions...

‣ Autophagy in Dementias

Kragh, Christine Lund; Ubhi, Kiren; Wyss-Corey, Tony; Masliah, Eliezer
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2012 Português
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Dementias are a varied group of disorders typically associated with memory loss, impaired judgment and/or language and by symptoms affecting other cognitive and social abilities to a degree that interferes with daily functioning. Alzheimer’s disease (AD) is the most common cause of a progressive dementia, followed by dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia (VaD) and HIV associated neurocognitive disorders (HAND).

‣ Amyloid Imaging in Dementias With Atypical Presentation

Wolk, David A.; Price, Julie C.; Madeira, Charles; Saxton, Judy A.; Snitz, Beth E.; Lopez, Oscar L.; Mathis, Chester A.; Klunk, William E.; DeKosky, Steven T.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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We explored the potential value of amyloid imaging in patients with atypical presentations of dementia. Twenty-eight patients with atypical dementia underwent PET imaging with the amyloid imaging tracer Pittsburgh Compound-B (PiB). Twenty-six had [18F]fluoro-2-deoxy-D-glucose (FDG) PET scans. After extensive clinical evaluation, this group of patients generated considerable diagnostic uncertainty and received working diagnoses that included possible AD (pAD), focal dementias [e.g. posterior cortical atrophy (PCA)], or cases in which no clear diagnostic category could be determined (dementia of uncertain etiology; DUE). Patients were classified as PiB-positive, -negative, or -intermediate based on objective criteria. Anterior-posterior (A-P) and left-right (L-R) indices of PiB and FDG uptake were calculated to examine differences in distribution of amyloid pathology and metabolic changes associated with clinical phenotype. Eleven patients (39%) were PiB-positive, 16 were PiB-negative (57%) and one (4%) was intermediate. By diagnostic category, 3/10 patients (30%) with DUE, 1/5 (20%) with primary progressive aphasia (PPA), 3/5 (60%) with posterior cortical atrophy (PCA), and 4/7 (57%) with pAD were PiB-positive. Brain metabolism of both PiB-positive and -negative patients were generally similar by phenotype...

‣ Are Clinical Diagnoses of Alzheimer’s Disease and Other Dementias Affected by Education and Self-Reported Race?

Teresi, Jeanne A.; Grober, Ellen; Eimicke, Joseph P.; Ehrlich, Amy R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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A randomized controlled trial examined whether the diagnostic process for Alzheimer’s disease and other dementias may be influenced by knowledge of the patient’s education and/or self-reported race. Four conditions were implemented: diagnostic team knows (a) race and education, (b) education only, (c) race only, or (d) neither. Diagnosis and clinical staging was established at baseline, at Wave 2, and for a random sample of Wave 3 respondents by a consensus panel. At study end, a longitudinal, “gold standard” diagnosis was made for patients with follow-up data (71%). Group differences in Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) diagnosis were estimated using logistic regression and generalized estimating equations. Sensitivity and specificity were examined for baseline diagnosis in relation to the gold standard, longitudinal diagnosis. Despite equivalent status on all measured variables across waves, members of the “knows race only” group were less likely than those of other groups to receive a diagnosis of dementia. At final diagnosis, 19% of the “knows race only” group was diagnosed with dementia versus 38% to 40% in the other 3 conditions (p = .038). Examination of sensitivities and specificities of baseline diagnosis in relation to the gold standard diagnosis showed a nonsignificant trend for lower sensitivities in the knowing race conditions (0.3846)...

‣ Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias

Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A.; Coomaraswamy, Janaky; Wirths, Oliver
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Familial British (FBD) and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu-) modified form, a mechanism which has been extensively described to be relevant for Aβ peptides in Alzheimer’s disease (AD). Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their non-modified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular and parenchymal deposits in human FBD and FDD brain tissue, as well as in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in pre-synaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in AD suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias.

‣ Cerebrospinal fluid amyloid-β 2-42 is decreased in Alzheimer’s, but not in frontotemporal dementia

Bibl, Mirko; Gallus, Marion; Welge, Volker; Esselmann, Hermann; Wolf, Stefanie; Rüther, Eckart; Wiltfang, Jens
Fonte: Springer Vienna Publicador: Springer Vienna
Tipo: Artigo de Revista Científica
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Alzheimer’s dementia (AD) and frontotemporal dementias (FTD) are common and their clinical differential diagnosis may be complicated by overlapping symptoms, which is why biomarkers may have an important role to play. Cerebrospinal fluids (CSF) Aβ2-42 and 1-42 have been shown to be similarly decreased in AD, but 1-42 did not display sufficient specificity for exclusion of other dementias from AD. The objective of the present study was to clarify the diagnostic value of Aβ2-42 peptides for the differential diagnosis of AD from FTD. For this purpose, 20 non-demented disease controls (NDC), 22 patients with AD and 17 with FTD were comparatively analysed by a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol with subsequent Aβ-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38ox, 2-40 and 2-42 along with Aβ 1-37, 1-38, 1-39, 1-40, 1-40ox and 1-42. CSF Aβ1-42 was decreased in AD as compared to NDC, but not to FTD. In a subgroup of the patients analyzed, the decrease of Abeta2-42 in AD was evident as compared to both NDC and FTD. Aβ1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aβ1-42 demonstrated sufficient diagnostic accuracies only when combined with Aβ1-38. Aβ2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aβ2-42 to Aβ1-38. Aβ2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias...

‣ Vascular Disease and Dementias: Paradigm Shifts to Drive Research in New Directions

Kling, Mitchel A.; Trojanowski, John Q.; Wolk, David A.; Lee, Virginia M.-Y.; Arnold, Steven E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. While these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging-related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the “Alzheimer-type,” and is observed more frequently than expected in postmortem material from individuals manifesting “specific” disease stigmata such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular vs. neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic...

‣ Incidence Rates of Dementia, Alzheimer’s disease and Vascular Dementia in the Japanese American Population in Seattle, WA: The Kame Project

Borenstein, AR; Wu, Y; Bowen, JD; McCormick, WM; Uomoto, J; McCurry, SM; Schellenberg, G; Larson, EB
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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There are few dementia incidence studies in representative minority populations in the U.S., and no population-based studies of Japanese American women. We identified 3,045 individuals aged 65+ with at least 1 parent of Japanese descent living in King County, WA in 1992–4, of which 1,836 were dementia-free and were examined every two years (1994–2001) to identify incident cases of all dementias, Alzheimer’s disease (AD), vascular dementia (VaD) and other dementias. Cox regression was used to examine associations with age, sex, years of education and Apolipoprotein (APOE)-ε4. Among 173 incident cases of dementia, the overall rate was 14.4/1,000/yr, with rates being slightly higher among women (15.9/1,000) than men (12.5/1,000). Rates roughly doubled every 5 years for dementia and AD; the age trend for VaD and other dementias was less consistent. Sex was not significantly related to incidence of dementia or its subtypes in adjusted models. There was a trend for an inverse association with increasing years of education. APOE-ε4 was a strong risk factor for all dementias (HR=2.89, 95% CI 1.88–4.46), AD (HR=3.27, 95% CI 2.03–5.28) and VaD (HR=3.33, 95% CI 1.34–8.27). This study is the first to report population-based incidence rates for both Japanese American men and women.

‣ Action versus animal naming fluency in subcortical dementia, frontal dementias, and Alzheimer’s disease

Davis, C.; Heidler-Gary, J.; Gottesman, R. F.; Crinion, J.; Newhart, M.; Moghekar, A.; Soloman, D.; Rigamonti, D.; Cloutman, L.; Hillis, A. E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Accumulating evidence indicates action naming may rely more on frontal-subcortical circuits, and noun naming may rely more on temporal cortex. Therefore, noun versus action fluency might distinguish frontal and subcortical dementias from cortical dementias primarily affecting temporal and/or parietal cortex such as Alzheimer’s disease (AD). We hypothesized patients with subcortical dementia, e.g., normal pressure hydrocephalus (NPH) and patients with dementias predominantly affecting frontal cortex, e.g., behavioral variant frontotemporal dementia (bv-FTD) and progressive nonfluent aphasia (PNFA) have more difficulty on action fluency versus noun fluency (e.g., animal naming). Patients with AD, who have temporo parietal cortical dysfunction, should have more difficulty on noun versus verb fluency. A total of 234 participants, including healthy controls (n = 20) and patients diagnosed with NPH (n =144), AD (n = 33), bv-FTD (n = 22) or PNFA (n = 15) were administered animal fluency, action fluency, and letter fluency tasks, and the Mini-Mental State Examination (MMSE, to control for dementia severity). NPH and bv-FTD/PNFA patients had significantly higher MMSE scores and animal fluency than AD patients (after adjusting for age), but their action fluency tended to be lower than in AD. Only NPH and bvFTD/PNFA patients showed significantly lower action verb than animal fluency. Results provide novel evidence that action naming relies more on frontal-subcortical circuits while noun naming relies more on temporoparietal cortex...

‣ Past Cigarette Smoking Is More Common among Those with Cholinergic Than Noncholinergic Dementias

Dalrymple, Kyle; Saito, Erin K.; Diaz, Natalie; Morrow, Julia; Nakamoto, Beau; McMurtray, Aaron M.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Background. Patients with progressive dementing disorders associated with cortical cholinergic dysfunction gradually develop cholinergic deficits many years before symptom onset and may begin to smoke cigarettes during midlife as a form of self-medication. The aim of this study was to compare self-reported past smoking rates between those with and without cholinergic dementias, to determine if those who developed cholinergic dementias were more likely to smoke during midlife than those who did not. Methods. Retrospective cross-sectional study of past smoking status among patients treated at an outpatient clinic during a three-year period. Results. A total of 440 patients were evaluated during the study period, including 224 with cholinergic dementias and 216 with noncholinergic dementias and controls. Past smoking rates were greater among those with cholinergic dementias compared to those without cholinergic dementias (43.92% versus 26.96%, P = 0.012). Additionally, smokers with cholinergic dementias reported significantly greater mean pack-years of smoking (P = 0.038). Conclusions. Greater midlife smoking rates and greater pack-years of smoking were associated with cholinergic dementias. These results suggest midlife smoking may be an early indicator for those developing brain cholinergic deficits related to progressive dementing disorders and support initiating treatment prior to symptom onset in cholinergic dementias.

‣ Functional Network Disruption in the Degenerative Dementias

Pievani, Michela; de Haan, Willem; Wu, Tao; Seeley, William W; Frisoni, Giovanni B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Despite considerable advances toward understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and the latter to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is critical for normal functioning. A better understanding of network disruption in the neurodegenerative dementias may help bridge the gap between molecular changes, pathology and symptoms. Recent findings on functional network disruption as assessed with “resting-state” or intrinsic connectivity fMRI and EEG/MEG have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are relatively specific to the clinical syndromes, and in Alzheimer's disease and frontotemporal dementia network disruption tracks the pattern of pathological changes. These findings may have a practical impact on diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the pre-symptomatic stage, and tracking of disease progression.

‣ Low blood pressure and dementia in elderly people: the Kungsholmen project.

Guo, Z.; Viitanen, M.; Fratiglioni, L.; Winblad, B.
Fonte: BMJ Group Publicador: BMJ Group
Tipo: Artigo de Revista Científica
Publicado em 30/03/1996 Português
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OBJECTIVE--To examine the relation between blood pressure and dementia in elderly people. DESIGN--Cross sectional, population based study. SETTING: Kungsholmen district of Stockholm, Sweden. SUBJECTS-- 1642 subjects aged 75-101 years. MAIN OUTCOME MEASURES--Prevalence and adjusted odds ratio of dementia by blood pressure. RESULTS--People with systolic pressure < or = 140 mm Hg were more often diagnosed as demented than those with systolic pressure >140 mm Hg: odds ratios (95% confidence interval) adjusted for age, sex, and education were 2.98 (2.17 to 4.08) for all dementias, 2.91 (1.93 to 4.38) for Alzheimer's disease, 2.00 (1.09 to 3.65) for vascular dementia, and 5.07 (2.65 to 9.70) for other dementias. Similar results were seen in subjects with diastolic pressure < or = 75 mm Hg compared with those with higher diastolic pressure. When severity and duration of dementia were taken into account, only moderate and severe dementia were found to be significantly related to relatively low blood pressure, and the association was stronger in subjects with longer disease duration. Use of hypotensive drugs and comorbidity with cardiovascular disease did not modify the results for all dementias, Alzheimer's disease, and other dementias but slightly reduced the association between vascular dementia and diastolic blood pressure. CONCLUSIONS--Both systolic and diastolic blood pressure were inversely related to prevalence of dementia in elderly people. We think that relatively low blood pressure is probably a complication of the dementia process...

‣ Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias

Beecham, Gary W.; Hamilton, Kara; Naj, Adam C.; Martin, Eden R.; Huentelman, Matt; Myers, Amanda J.; Corneveaux, Jason J.; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G.; Bennett, David A.; De Jager, Philip L.; Larson, Eric B.; Crane, Paul K.; Kamb
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/09/2014 Português
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Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1...

‣ Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Dementias

Hsu, Yuan-Yu; Du, An-Tao; Schuff, Norbert; Weiner, Michael W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2001 Português
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This article reviews recent studies of magnetic resonance imaging and magnetic resonance spectroscopy in dementia, including Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, idiopathic Parkinson's disease, Huntington's disease, and vascular dementia. Magnetic resonance imaging and magnetic resonance spectroscopy can detect structural alteration and biochemical abnormalities in the brain of demented subjects and may help in the differential diagnosis and early detection of affected individuals, monitoring disease progression, and evaluation of therapeutic effect.

‣ Key Neuropsychiatric Symptoms in Common Dementias: Prevalence and Implications for Caregivers, Clinicians, and Health Systems

Sadak, Tatiana I.; Katon, Jodie; Beck, Cornelia; Cochrane, Barbara B.; Borson, Soo
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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The purpose of this study was to compare neuropsychiatric symptoms (NPS) among people with common dementias and equip interdisciplinary clinicians and health services planners with large-sample data necessary to plan care for patients and families. We analyzed selected variables from baseline assessments of older adults with dementia of one or more etiologies (N = 3,768) from the National Alzheimer's Coordinating Center data repository. Dementias included Alzheimer's disease (AD), Lewy body dementia (DLB), behavioral variant frontotemporal dementia (bvFTD), and vascular dementia (VaD). We compared the prevalence of four NPS clusters (agitation/aggression, depression/dysphoria, anxiety, irritability/lability) across dementia etiologies and stages using logistic regression and AD as the reference group. NPS profiles differed significantly across dementia types and stages. Compared with primary AD, DLB was associated with greater odds of depression/dysphoria (OR = 1.68, 95% confidence interval [CI] 1.28, 2.20) and anxiety (OR = 1.80, 95% CI 1.37, 2.36), with similar findings when DLB was diagnosed in combination with AD (depression/dysphoria: OR = 1.79, 95% CI 1.11, 2.89; anxiety: OR = 1.88, 95% CI 1.17, 3.02). Primary bvFTD was associated with greater odds of agitation/aggression (OR = 1.59...