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1.
Ron Brookmeyer Nada Abdalla Claudia H. Kawas María M. Corrada 《Alzheimer's & dementia》2018,14(2):121-129
Introduction
We forecast the prevalence of preclinical and clinical Alzheimer's disease (AD) and evaluated potential impacts of primary and secondary preventions in the United States.Methods
We used a multistate model incorporating biomarkers for preclinical AD with US population projections.Results
Approximately 6.08 million Americans had either clinical AD or mild cognitive impairment due to AD in 2017 and that will grow to 15.0 million by 2060. In 2017, 46.7 million Americans had preclinical AD (amyloidosis, neurodegeneration, or both), although many may not progress to clinical disease during their lifetimes. Primary and secondary preventions have differential impact on future disease burden.Discussion
Because large numbers of persons are living with preclinical AD, our results underscore the need for secondary preventions for persons with existing AD brain pathology who are likely to develop clinical disease during their lifetimes as well as primary preventions for persons without preclinical disease. 相似文献2.
Sarah H. Stout Ganesh M. Babulal Chunyu Ma David B. Carr Denise M. Head Elizabeth A. Grant Monique M. Williams David M. Holtzman Anne M. Fagan John C. Morris Catherine M. Roe 《Alzheimer's & dementia》2018,14(5):610-616
Introduction
With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimer's disease (AD) older adults stop driving and whether preclinical AD affects driving cessation.Methods
Time to driving cessation was examined based on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795 older adults followed up to 24 years received CDR ratings. A subset (591) had cerebrospinal fluid biomarker measurements and was followed up to 17 years. Differences in CDR and biomarker groups as predictors of time to driving cessation were analyzed using Kaplan-Meier curves and Cox proportional models.Results
Higher CDR scores and more abnormal biomarker measurements predicted a shorter time to driving cessation.Discussion
Higher levels of AD biomarkers, including among individuals with preclinical AD, lead to earlier driving cessation. Negative functional outcomes of preclinical AD show a nonbenign phase of the disease. 相似文献3.
Ann D. Cohen Eric McDade Brad Christian Julie Price Chester Mathis William Klunk Benjamin L. Handen 《Alzheimer's & dementia》2018,14(6):743-750
Introduction
The objective of this study was to evaluate amyloid β (Aβ) deposition patterns in different groups of cerebral β amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Aβ clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Aβ clearance (preclinical AD).Methods
We performed whole-brain voxelwise comparison of cerebral Aβ between 23 Down syndrome, 10 preclinical autosomal dominant Alzheimer disease, 17 late-onset AD, and 16 preclinical AD subjects, using Pittsburgh Compound B–positron emission tomography.Results
We found both Down syndrome and preclinical autosomal dominant Alzheimer disease shared a distinct pattern of increased bilateral striatal and thalamic Aβ deposition compared to late-onset AD and preclinical AD.Conclusion
Disorders associated with early-life alterations in amyloid precursor protein production or processing are associated with a distinct pattern of early striatal fibrillary Aβ deposition before significant cognitive impairment. A better understanding of this unique pattern could identify important mechanisms of Aβ deposition and possibly important targets for early intervention. 相似文献4.
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5.
Michelle M. Mielke Clinton E. Hagen Jing Xu Xiyun Chai Prashanthi Vemuri Val J. Lowe David C. Airey David S. Knopman Rosebud O. Roberts Mary M. Machulda Clifford R. Jack Ronald C. Petersen Jeffrey L. Dage 《Alzheimer's & dementia》2018,14(8):989-997
Introduction
We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ.Methods
Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181.Results
Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE).Discussion
Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. 相似文献6.
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7.
Jianping Jia Cuibai Wei Shuoqi Chen Fangyu Li Yi Tang Wei Qin Lina Zhao Hongmei Jin Hui Xu Fen Wang Aihong Zhou Xiumei Zuo Liyong Wu Ying Han Yue Han Liyuan Huang Qi Wang Dan Li Serge Gauthier 《Alzheimer's & dementia》2018,14(4):483-491
Introduction
The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain.Methods
We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD.Results
The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015.Discussion
China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide. 相似文献8.
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
Introduction
Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD.Methods
AD neuropathogenic proteins Aβ1–42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls.Results
Neuronal exosome levels of Aβ1–42, P-T181-tau, and P-S396-tau were significantly elevated in individuals with DS compared with age-matched controls at all ages beginning in childhood. No significant gender differences were observed.Discussion
These early increases in Aβ1–42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available. 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.
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11.
Andrea Vergallo René-Sosata Bun Nicola Toschi Filippo Baldacci Henrik Zetterberg Kaj Blennow Enrica Cavedo Foudil Lamari Marie-Odile Habert Bruno Dubois Roberto Floris Francesco Garaci Simone Lista Harald Hampel 《Alzheimer's & dementia》2018,14(12):1623-1631
Introduction
Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls.Methods
The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD).Results
We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations.Discussion
Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease. 相似文献12.
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13.
Stephan Müller Oliver Preische Hamid R. Sohrabi Susanne Gräber Mathias Jucker John M. Ringman Ralph N. Martins Eric McDade Peter R. Schofield Bernardino Ghetti Martin Rossor Nick N. Fox Neill R. Graff-Radford Johannes Levin Adrian Danek Jonathan Vöglein Stephen Salloway Chengjie Xiong Christoph Laske 《Alzheimer's & dementia》2018,14(11):1427-1437
Introduction
Little is known about effects of physical activity (PA) in genetically driven early-onset autosomal dominant Alzheimer's disease (AD).Methods
A total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross-sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations.Results
Mutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD-like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.Discussion
These results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD. 相似文献14.
Sirwan K.L. Darweesh Frank J. Wolters M. Arfan Ikram Frank de Wolf Daniel Bos Albert Hofman 《Alzheimer's & dementia》2018,14(11):1450-1459
Introduction
Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of developing dementia.Methods
We searched PubMed, Embase, and Cochrane library for prospective population-based studies reporting associations between inflammatory markers and all-cause dementia or AD. We used random effects meta-analyses to obtain pooled hazard ratios (HRs) and 95% confidence intervals of inflammatory markers (highest vs. lowest quantile) for all-cause dementia and AD.Results
Fifteen articles from 13 studies in six countries reported data that could be meta-analyzed. C-reactive protein (HR = 1.37 [1.05; 1.78]), interleukin-6 (HR = 1.40 [1.13; 1.73]), α1-antichymotrypsin (HR = 1.54 [1.14; 2.80]), lipoprotein-associated phospholipase A2 activity (HR = 1.40 [1.03; 1.90]), and fibrinogen were each associated with all-cause dementia, but neither was significantly associated with AD.Discussion
Several inflammatory markers are associated with an increased risk of all-cause dementia; however, these markers are not specific for AD. Whether inflammatory markers closely involved in AD pathology are associated with the risk of AD remains to be elucidated. 相似文献15.
Rebecca A. Nebel Neelum T. Aggarwal Lisa L. Barnes Aimee Gallagher Jill M. Goldstein Kejal Kantarci Monica P. Mallampalli Elizabeth C. Mormino Laura Scott Wai Haung Yu Pauline M. Maki Michelle M. Mielke 《Alzheimer's & dementia》2018,14(9):1171-1183
Introduction
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches.Methods
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.Results
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.Discussion
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes. 相似文献16.
Victor Montal Eduard Vilaplana Daniel Alcolea Jordi Pegueroles Ofer Pasternak Sofia González-Ortiz Jordi Clarimón María Carmona-Iragui Ignacio Illán-Gala Estrella Morenas-Rodríguez Roser Ribosa-Nogué Isabel Sala María-Belén Sánchez-Saudinós Maite García-Sebastian Jorge Villanúa Andrea Izagirre Ainara Estanga Mirian Ecay-Torres Juan Fortea 《Alzheimer's & dementia》2018,14(3):340-351
Introduction
Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD).Methods
We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum.Results
Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages.Discussion
These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification. 相似文献17.
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18.
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19.
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20.
Alberto Benussi Valentina Dell&#x;Era Valentina Cantoni Clarissa Ferrari Salvatore Caratozzolo Luca Rozzini Antonella Alberici Alessandro Padovani Barbara Borroni 《Brain stimulation》2018,11(2):366-373