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1.
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2.
Alexander N.W. Taylor Lana Kambeitz-Ilankovic Benno Gesierich Lee Simon-Vermot Nicolai Franzmeier Miguel Á. Araque Caballero Sophia Müller Liu Hesheng Birgit Ertl-Wagner Katharina Bürger Michael W. Weiner Martin Dichgans Marco Duering Michael Ewers 《Alzheimer's & dementia》2017,13(3):225-235
Introduction
White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.Method
Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).Results
WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.Conclusions
High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function. 相似文献3.
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4.
Catherine Feart Catherine Helmer Bénédicte Merle François R. Herrmann Cédric Annweiler Jean-François Dartigues Cécile Delcourt Cécilia Samieri 《Alzheimer's & dementia》2017,13(11):1207-1216
Introduction
Hypovitaminosis D has been associated with several chronic conditions; yet, its association with cognitive decline and the risk of dementia and Alzheimer's disease (AD) has been inconsistent.Methods
The study population consisted of 916 participants from the Three-City Bordeaux cohort aged 65+, nondemented at baseline, with assessment of vitamin D status and who were followed for up to 12 years.Results
In multivariate analysis, compared with individuals with 25(OH)D sufficiency (n = 151), participants with 25(OH)D deficiency (n = 218) exhibited a faster cognitive decline. A total of 177 dementia cases (124 AD) occurred: 25(OH)D deficiency was associated with a nearly three-fold increased risk of AD (hazard ratio = 2.85, 95% confidence interval 1.37–5.97).Discussion
This large prospective study of French older adults suggests that maintaining adequate vitamin D status in older age could contribute to slow down cognitive decline and to delay or prevent the onset of dementia, especially of AD etiology. 相似文献5.
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6.
Thanh G.N. Ton Thomas DeLeire Suepattra G. May Ningqi Hou Mahlet G. Tebeka Er Chen Joshua Chodosh 《Alzheimer's & dementia》2017,13(3):217-224
Introduction
Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia.Methods
With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross-sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns.Results
Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018).Discussion
Patients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits. 相似文献7.
Hugh C. Hendrie Mengjie Zheng Wei Li Kathleen Lane Roberta Ambuehl Christianna Purnell Frederick W. Unverzagt Alexia Torke Ashok Balasubramanyam Chris M. Callahan Sujuan Gao 《Alzheimer's & dementia》2017,13(2):111-118
Introduction
High blood glucose levels may be responsible for the increased risk for dementia in diabetic patients.Methods
A secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis–Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables.Results
Diabetic participants who developed incident dementia had a significant decrease in serum glucose levels in the years preceding the diagnosis compared to the participants with normal cognition (P = .0002). They also had significantly higher glucose levels up to 9 years before the dementia diagnosis (P = .0367).Discussion
High glucose levels followed by a decline occurring years before diagnosis in African American participants with diabetes may represent a powerful presymptomatic metabolic indicator of dementia. 相似文献8.
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9.
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10.
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11.
Vincent Chouraki Sarah R. Preis Qiong Yang Alexa Beiser Shuo Li Martin G. Larson Galit Weinstein Thomas J. Wang Robert E. Gerszten Ramachandran S. Vasan Sudha Seshadri 《Alzheimer's & dementia》2017,13(12):1327-1336
Introduction
The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics.Methods
Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models.Results
Ninety-three participants developed incident dementia (mean follow-up = 15.6 ± 5.2 years). Higher plasma anthranilic acid levels were associated with greater risk of dementia (hazard ratio [HR] = 1.40; 95% confidence interval [CI] = [1.15–1.70]; P = 8.08 × 10?4). Glutamic acid (HR = 1.38; 95% CI = [1.11–1.72]), taurine (HR = 0.74; 95% CI = [0.60–0.92]), and hypoxanthine (HR = 0.74; 95% CI = [0.60–0.92]) levels also showed suggestive associations with dementia risk.Discussion
We identified four biologically plausible, candidate plasma biomarkers for dementia. Association of anthranilic acid implicates the kynurenine pathway, which modulates glutamate excitotoxicity. The associations with hypoxanthine and taurine strengthen evidence that uric acid and taurine may be neuroprotective. 相似文献12.
Richard A. Goodman Kimberly A. Lochner Madhav Thambisetty Thomas S. Wingo Samuel F. Posner Shari M. Ling 《Alzheimer's & dementia》2017,13(1):28-37
Introduction
Rapid growth of the older adult population requires greater epidemiologic characterization of dementia. We developed national prevalence estimates of diagnosed dementia and subtypes in the highest risk United States (US) population.Methods
We analyzed Centers for Medicare & Medicaid administrative enrollment and claims data for 100% of Medicare fee-for-service beneficiaries enrolled during 2011–2013 and age ≥68 years as of December 31, 2013 (n = 21.6 million).Results
Over 3.1 million (14.4%) beneficiaries had a claim for a service and/or treatment for any dementia subtype. Dementia not otherwise specified was the most common diagnosis (present in 92.9%). The most common subtype was Alzheimer's (43.5%), followed by vascular (14.5%), Lewy body (5.4%), frontotemporal (1.0%), and alcohol induced (0.7%). The prevalence of other types of diagnosed dementia was 0.2%.Discussion
This study is the first to document concurrent prevalence of primary dementia subtypes among this US population. The findings can assist in prioritizing dementia research, clinical services, and caregiving resources. 相似文献13.
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14.
Jianping Jia Serge Gauthier Sarah Pallotta Yong Ji Wenshi Wei Shifu Xiao Dantao Peng Qihao Guo Liyong Wu Shengdi Chen Weihong Kuang Junjian Zhang Cuibai Wei Yi Tang 《Alzheimer's & dementia》2017,13(5):592-597
Introduction
Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD).Methods
Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted.Results
Literature review showed that RCD definitions varied. Mini-Mental State Examination scores <20 at treatment onset, vascular risk factors, age <70 years at symptom onset, higher education levels, and early appearance of hallucinations, psychosis, or extrapyramidal symptoms are recognized RCD risk factors. Chart review showed that RCD (Mini-Mental State Examination score decline ≥3 points/year) is more common in moderate (43.2%) than in mild patients (20.1%; P < .001). Rapid and slow decliners had similar age, gender, and education levels at baseline.Discussion
RCD is sufficiently common to interfere with randomized clinical trials. We propose a 6-month prerandomization determination of the decline rate or use of an RCD risk score to ensure balanced allocation among treatment groups. 相似文献15.
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16.
Anders Wimo Maëlenn Guerchet Gemma-Claire Ali Yu-Tzu Wu A. Matthew Prina Bengt Winblad Linus Jönsson Zhaorui Liu Martin Prince 《Alzheimer's & dementia》2017,13(1):1-7
Introduction
In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates.Methods
This is a societal, prevalence-based global COI study.Results
The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018.Discussion
Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs. 相似文献17.
Kieu T.T. Phung Monique Chaaya Martin Prince Samir Atweh Khalil El Asmar Georges Karam Rose Mary Khoury Lilian Ghandour Husam Ghusn T. Rune Nielsen Gunhild Waldemar 《Alzheimer's & dementia》2017,13(12):1317-1326
Introduction
In North Africa and the Middle East, studies about dementia prevalence are scarce. A pilot study was conducted in Lebanon to assess dementia prevalence, using the Arabic-validated 10/66 Dementia Research Group (DRG) diagnostic assessment for case ascertainment. The study also examined care arrangement and access to care.Methods
A random sample of 502 persons older than 65 years and their informant were recruited from Beirut and Mount Lebanon governorates through multistage cluster sampling.Results
The crude and age-standardized dementia prevalences were 7.4% and 9.0%, respectively. People with dementia were mainly cared for by relatives at home. Access to formal care was very limited.Discussion
Dementia prevalence in Lebanon ranks high within the global range of estimates. These first evidence-based data about disease burden and barriers to care serve to raise awareness and call for social and health care reform to tackle the dementia epidemic in Lebanon and in North Africa and the Middle East. 相似文献18.
Stephanie Kielb Emily Rogalski Sandra Weintraub Alfred Rademaker 《Alzheimer's & dementia》2017,13(12):1337-1344
Introduction
Functional and cognitive features of subjective cognitive decline (SCD) were identified in a longitudinal database from the National Alzheimer's Coordinating Center.Methods
Cognitively normal older adults with (SCD+) and without (SCD?) self-reported memory complaints (N = 3915) were compared on (1) baseline Functional Assessment Questionnaire ratings, (2) baseline scores and longitudinal rate of change estimates from nine neuropsychological tests, and (3) final clinical diagnoses.Results
SCD+ had higher baseline ratings of functional impairment, reduced episodic memory practice effects and poorer performance on neuropsychological tests of psychomotor speed and language, and higher frequencies of mild cognitive impairment and dementia diagnoses at the end of follow-up compared with the SCD-group.Discussion
Subtle clinical features of SCD identified in this large cohort are difficult to detect at the individual level. More sensitive tests are needed to identify those with SCD who are vulnerable to cognitive decline and dementia. 相似文献19.
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20.
Eric D. Hamlett Edward J. Goetzl Aurélie Ledreux Vitaly Vasilevko Heather A. Boger Angela LaRosa David Clark Steven L. Carroll María Carmona-Iragui Juan Fortea Elliott J. Mufson Marwan Sabbagh Abdul H. Mohammed Dean Hartley Eric Doran Ira T. Lott Ann-Charlotte Granholm 《Alzheimer's & dementia》2017,13(5):541-549