共查询到20条相似文献，搜索用时 31 毫秒
1.
Lidia Sarro Nirubol Tosakulwong Christopher G. Schwarz Jonathan Graff-Radford Scott A. Przybelski Timothy G. Lesnick Samantha M. Zuk Robert I. Reid Mekala R. Raman Bradley F. Boeve Tanis J. Ferman David S. Knopman Giancarlo Comi Massimo Filippi Melissa E. Murray Joseph E. Parisi Dennis W. Dickson Ronald C. Petersen Kejal Kantarci 《Alzheimer's & dementia》2017,13(3):257-266
Introduction
Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB).Methods
White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort.Results
DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia.Discussion
In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease. 相似文献2.
Austyn Roseborough Joel Ramirez Sandra E. Black Jodi D. Edwards 《Alzheimer's & dementia》2017,13(10):1154-1167
Introduction
This systematic review synthesizes current evidence for associations between cortical amyloid β, visualized on amyloid positron emission tomography imaging, and white matter hyperintensity (WMH) burden on magnetic resonance imaging in healthy elderly adults and individuals with cognitive impairment and dementia.Methods
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review guidelines, we systematically searched MEDLINE, Embase, Cochrane, and PsycINFO databases from January 2000 to September 2015.Results
Our search returned 492 articles, 34 of which met criteria for inclusion in the final selection. Most studies reported no significant relationships between amyloid β and WMH burden across diagnostic groups.Discussion
Findings of this systematic review suggest that amyloid accumulation and WMH are independent but additive processes. The limited number of independent cohorts, lack of longitudinal data, and exclusion of individuals with mixed dementia limit the generalizability of these findings. Further studies are required to elucidate the putative contributions of vascular processes to neurodegenerative pathology. 相似文献3.
Hiroko H. Dodge Jian Zhu Randy Woltjer Peter T. Nelson David A. Bennett Nigel J. Cairns David W. Fardo Jeffrey A. Kaye Deniz-Erten Lyons Nora Mattek Julie A. Schneider Lisa C. Silbert Chengjie Xiong Lei Yu Frederick A. Schmitt Richard J. Kryscio Erin L. Abner 《Alzheimer's & dementia》2017,13(6):613-623
Introduction
The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).Methods
We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts).Results
The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low.Discussion
Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required. 相似文献4.
Joanna M. Wardlaw Stephen J. Makin Maria C. Valdés Hernández Paul A. Armitage Anna K. Heye Francesca M. Chappell Susana Muñoz-Maniega Eleni Sakka Kirsten Shuler Martin S. Dennis Michael J. Thrippleton 《Alzheimer's & dementia》2017,13(6):634-643
Introduction
Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.Methods
We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.Results
In 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.Discussion
BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia. 相似文献5.
Panos Theofilas Alexander J. Ehrenberg Sara Dunlop Ana T. Di Lorenzo Alho Austin Nguy Renata Elaine Paraizo Leite Roberta Diehl Rodriguez Maria B. Mejia Claudia K. Suemoto Renata Eloah De Lucena Ferretti-Rebustini Livia Polichiso Camila F. Nascimento William W. Seeley Ricardo Nitrini Carlos Augusto Pasqualucci Wilson Jacob Filho Udo Rueb John Neuhaus Lea T. Grinberg 《Alzheimer's & dementia》2017,13(3):236-246
Introduction
Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]).Methods
The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.Results
As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC.Discussion
The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages. 相似文献6.
Clifford R. Jack Heather J. Wiste Stephen D. Weigand Terry M. Therneau Val J. Lowe David S. Knopman Jeffrey L. Gunter Matthew L. Senjem David T. Jones Kejal Kantarci Mary M. Machulda Michelle M. Mielke Rosebud O. Roberts Prashanthi Vemuri Denise A. Reyes Ronald C. Petersen 《Alzheimer's & dementia》2017,13(3):205-216
Introduction
Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.Methods
We examined five methods for determining cut points.Results
The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.Discussion
In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method. 相似文献7.
Sean M. Nestor Bratislav Mišić Joel Ramirez Jiali Zhao Simon J. Graham Nicolaas P.L.G. Verhoeff Donald T. Stuss Mario Masellis Sandra E. Black 《Alzheimer's & dementia》2017,13(7):749-760
Introduction
Cerebral small vessel disease (SVD) is thought to contribute to Alzheimer's disease (AD) through abnormalities in white matter networks. Gray matter (GM) hub covariance networks share only partial overlap with white matter connectivity, and their relationship with SVD has not been examined in AD.Methods
We developed a multivariate analytical pipeline to elucidate the cortical GM thickness systems that covary with major network hubs and assessed whether SVD and neurodegenerative pathologic markers were associated with attenuated covariance network integrity in mild AD and normal elderly control subjects.Results
SVD burden was associated with reduced posterior cingulate corticocortical GM network integrity and subneocorticocortical hub network integrity in AD.Discussion
These findings provide evidence that SVD is linked to the selective disruption of cortical hub GM networks in AD brains and point to the need to consider GM hub covariance networks when assessing network disruption in mixed disease. 相似文献8.
Anna E. Leeuwis Marije R. Benedictus Joost P.A. Kuijer Maja A.A. Binnewijzend Astrid M. Hooghiemstra Sander C.J. Verfaillie Teddy Koene Philip Scheltens Frederik Barkhof Niels D. Prins Wiesje M. van der Flier 《Alzheimer's & dementia》2017,13(5):531-540
Introduction
We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD).Methods
We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume–corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains. Associations were investigated using linear regression analyses.Results
In the whole sample, reduced overall and regional CBF was associated with impairment in all cognitive domains. We found significant interactions between diagnosis and CBF for language and between diagnosis and parietal CBF for global cognition and executive functioning. Stratification showed that decreased CBF was associated with worse performance in AD patients but not in MCI or SCD.Discussion
Our results suggest that CBF may have potential as a functional marker of disease severity. 相似文献9.
Jordi Pegueroles Eduard Vilaplana Victor Montal Frederic Sampedro Daniel Alcolea Maria Carmona-Iragui Jordi Clarimon Rafael Blesa Alberto Lleó Juan Fortea 《Alzheimer's & dementia》2017,13(5):499-509
Introduction
Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.Methods
We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates.Results
At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1–42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1–42 levels.Discussion
Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy. 相似文献10.
11.
Diego Mastroeni Omar M. Khdour Elaine Delvaux Jennifer Nolz Gary Olsen Nicole Berchtold Carl Cotman Sidney M. Hecht Paul D. Coleman 《Alzheimer's & dementia》2017,13(5):510-519
Introduction
We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I–V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's disease (AD) subjects.Methods
Hippocampal tissues from 44 non-AD controls (NC), 10 amnestic MCI, and 18 AD cases were analyzed on Affymetrix Hg-U133 plus 2.0 arrays.Results
The microarray data revealed significant down regulation in OXPHOS genes in AD, particularly those encoded in the nucleus. In contrast, there was up regulation of the same gene(s) in MCI subjects compared to AD and ND cases. No significant differences were observed in mtDNA genes identified in the array between AD, ND, and MCI subjects except one mt-ND6.Discussion
Our findings suggest that restoration of the expression of nuclear-encoded OXPHOS genes in aging could be a viable strategy for blunting AD progression. 相似文献12.
Belinda M. Brown Hamid R. Sohrabi Kevin Taddei Samantha L. Gardener Stephanie R. Rainey-Smith Jeremiah J. Peiffer Chengjie Xiong Anne M. Fagan Tammie Benzinger Virginia Buckles Kirk I. Erickson Roger Clarnette Tejal Shah Colin L. Masters Michael Weiner Nigel Cairns Martin Rossor Neill R. Graff-Radford Ralph N. Martins 《Alzheimer's & dementia》2017,13(11):1197-1206
Introduction
The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers.Methods
In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression.Results
No differences in brain amyloid load, CSF Aβ42, or CSF tau were observed between low and high exercise groups. Nevertheless, when examining only those already accumulating AD pathology (i.e., amyloid positive), low exercisers had higher mean levels of brain amyloid than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset was a significant predictor of brain amyloid levels.Discussion
Our findings indicate a relationship exists between self-reported exercise levels and brain amyloid in autosomal dominant AD mutation carriers. 相似文献13.
Mariella Lauriola Roberto Esposito Stefano Delli Pizzi Massimiliano de Zambotti Francesco Londrillo Joel H. Kramer Gil D. Rabinovici Armando Tartaro 《Alzheimer's & dementia》2017,13(7):783-791
Introduction
Subjective cognitive decline (SCD) is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Although sleep has been shown to be altered in MCI and AD, little is known about sleep in SCD.Methods
Seventy cognitively normal community-dwelling participants were classified as SCD (32) or controls (38) using the Subjective Cognitive Decline Questionnaire. Sleep was assessed using actigraphy and diaries. FreeSurfer was used for performing medial temporal lobes (MTLs) and brain cortical parcellation of 3T magnetic resonance images. Multiple regression models were used to assess the presence of sleep, MTL, or regional cortical differences between groups.Results
Objective sleep was disrupted in SCD participants, which showed increased nighttime wakefulness and reduced sleep efficiency. No group differences emerged in subjective sleep or magnetic resonance imaging outcomes.Discussion
Objective sleep resulted disrupted in community-dwelling SCD, without any subjective sleep or cortical change. Sleep assessment/intervention in SCD might help prevent/delay AD onset. 相似文献14.
Laura Frain David Swanson Kelly Cho David Gagnon Kun Ping Lu Rebecca A. Betensky Jane Driver 《Alzheimer's & dementia》2017,13(12):1364-1370
Introduction
To examine the risk of Alzheimer's disease (AD) among cancer survivors in a national database.Methods
Retrospective cohort of 3,499,378 mostly male US veterans aged ≥65 years were followed between 1996 and 2011. We used Cox models to estimate risk of AD and alternative outcomes (non-AD dementia, osteoarthritis, stroke, and macular degeneration) in veterans with and without a history of cancer.Results
Survivors of a wide variety of cancers had modestly lower AD risk, but increased risk of the alternative outcomes. Survivors of screened cancers, including prostate cancer, had a slightly increased AD risk. Cancer treatment was independently associated with decreased AD risk; those who received chemotherapy had a lower risk than those who did not.Discussion
Survivors of some cancers have a lower risk of AD but not other age-related conditions, arguing that lower AD diagnosis is not simply due to bias. Cancer treatment may be associated with decreased risk of AD. 相似文献15.
Tharick A. Pascoal Sulantha Mathotaarachchi Monica Shin Andrea L. Benedet Sara Mohades Seqian Wang Tom Beaudry Min Su Kang Jean-Paul Soucy Aurelie Labbe Serge Gauthier Pedro Rosa-Neto 《Alzheimer's & dementia》2017,13(6):644-653
Introduction
Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia.Methods
We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers.Results
We found that the synergism between [18F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD.Discussion
Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins. 相似文献16.
Yaakov Stern Yian Gu Stephanie Cosentino Martina Azar Siobhan Lawless Oksana Tatarina 《Alzheimer's & dementia》2017,13(1):20-27
Introduction
The Predictors study was designed to predict the length of time to major disease outcomes in Alzheimer's disease (AD) patients. Here, we describe the development of a new, Predictors 3, cohort.Methods
Patients with prevalent or incident AD and individuals at-risk for developing AD were selected from the North Manhattan community and followed annually with instruments comparable to those used in the original two Predictors cohorts.Results
The original Predictors cohorts were clinic based and racially/ethnically homogenous (94% white, 6% black; 3% Hispanic). In contrast, the 274 elders in this cohort are community-based and ethnically diverse (39% white, 40% black, 21% other; 78% Hispanic). Confirming previous observations, psychotic features were associated with poorer function and mental status and extrapyramidal signs with poorer function.Discussion
This new cohort will allow us to test observations made in our original clinic-based cohorts in patients that may be more representative of the general community. 相似文献17.
Carly Oboudiyat Tamar Gefen Eleni Varelas Sandra Weintraub Emily Rogalski Eileen H. Bigio M.-Marsel Mesulam 《Alzheimer's & dementia》2017,13(5):598-601
Introduction
The accuracy of cerebrospinal fluid (CSF) biomarkers for detecting Alzheimer's disease (AD) pathology has not been fully validated in autopsied nonamnestic dementias.Methods
We retrospectively evaluated CSF amyloid β 1–42, phosphorylated-tau, and amyloid-tau index as predictors of Alzheimer pathology in patients with primary progressive aphasia, frontotemporal dementia, and progressive supranuclear palsy.Results
Nineteen nonamnestic autopsied cases with relevant CSF values were included. At autopsy, nine had AD and 10 had non-AD pathologies. All six patients whose combined CSF phosphorylated-tau and amyloid β levels were “consistent with AD” had postmortem Alzheimer pathology. The two patients whose biomarker values were “not consistent with AD” had non-AD pathologies. The CSF values of the remaining eight non-AD cases were in conflicting or borderline ranges.Discussion
CSF biomarkers reliably identified Alzheimer pathology in nonamnestic dementias and may be useful as a screening measure for inclusion of nonamnestic cases into Alzheimer's trials. 相似文献18.
José L. Molinuevo Laura A. Rabin Rebecca Amariglio Rachel Buckley Bruno Dubois Kathryn A. Ellis Michael Ewers Harald Hampel Stefan Klöppel Lorena Rami Barry Reisberg Andrew J. Saykin Sietske Sikkes Colette M. Smart Beth E. Snitz Reisa Sperling Wiesje M. van der Flier Michael Wagner Frank Jessen 《Alzheimer's & dementia》2017,13(3):296-311
Introduction
Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed.Methods
Members of the SCD-I met to identify and agree on topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly.Results
Topics included SCD inclusion and exclusion criteria, together with the informant's role in defining SCD presence and the impact of demographic factors.Discussion
Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies. 相似文献19.
Marc Teichmann Stéphane Epelbaum Dalila Samri Marcel Levy Nogueira Agnès Michon Harald Hampel Foudil Lamari Bruno Dubois 《Alzheimer's & dementia》2017,13(8):913-923
Introduction
The International Working Group recommended the Free and Cued Selective Reminding Test (FCSRT) as a sensitive detector of the amnesic syndrome of the hippocampal type in typical Alzheimer's disease (AD). But does it differentiate AD from other neurodegenerative diseases?Methods
We assessed the FCSRT and cerebrospinal fluid (CSF) AD biomarkers in 992 cases. Experts, blinded to biomarker data, attributed in 650 cases a diagnosis of typical AD, frontotemporal dementia, posterior cortical atrophy, Lewy body disease, progressive supranuclear palsy, corticobasal syndrome, primary progressive aphasias, “subjective cognitive decline,” or depression.Results
The FCSRT distinguished typical AD from all other conditions with a sensitivity of 100% and a specificity of 75%. Non-AD neurodegenerative diseases with positive AD CSF biomarkers (“atypical AD”) did not have lower FCSRT scores than those with negative biomarkers.Discussion
The FCSRT is a reliable tool for diagnosing typical AD among various neurodegenerative diseases. At an individual level, however, its specificity is not absolute. Our findings also widen the spectrum of atypical AD to multiple neurodegenerative conditions. 相似文献20.
Rui Wang Laura Fratiglioni Grégoria Kalpouzos Martin Lövdén Erika J. Laukka Lena Bronge Lars-Olof Wahlund Lars Bäckman Chengxuan Qiu 《Alzheimer's & dementia》2017,13(3):247-256