Harvard Aging Brain Study: Dataset and accessibility

Dagley, Alexander; LaPoint, Molly R.; Huijbers, Willem; Hedden, Trey; McLaren, Donald G.; Chatwal, Jasmeer P.; Papp, Kathryn V.; Amariglio, Rebecca E.; Blacker, Deborah; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Schultz, Aaron P.

doi:10.1016/j.neuroimage.2015.03.069

Cited by 154 publications

(175 citation statements)

References 18 publications

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“…RESULTS Demographics for the study population were similar to those reported for the larger HAB study 24 (tables 1 and e-1). No significant differences between the study population and the larger HAB sample were observed with respect to age, APOE e4 status, sex, MMSE, Logical memory Immediate and Delayed Recall, or Trails A (all p .…”

Section: 21supporting

confidence: 56%

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

et al. 2016

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Objective: To better understand cross-sectional relationships between CSF and PET measures of tau pathology, we compared regional and global measures of 18 F-T807 (AV-1451) PET to CSF protein levels of total tau (t-tau), phosphorylated tau (p-tau), and b-amyloid 1-42 (Ab42).Methods: T-tau, p-tau, and Ab42 levels were assessed using INNOTEST xMAP immunoassays.Linear regression was used to compare regional and global measures of 18 F-T807 standardized uptake value ratios (SUVR) to CSF protein levels using data from 31 cognitively unimpaired elderly participants in the Harvard Aging Brain study.Results: After controlling for sex and age, total cortical 18 F-T807 binding was significantly correlated with p-tau (partial r 5 0.48; p , 0.01) and at trend level with t-tau (partial r 5 0.30; p 5 0.12). Regional 18 F-T807 measures were more strongly correlated with CSF protein levels than the global measure, with both t-tau and p-tau significantly correlated with 18 F-T807 SUVR in entorhinal, parahippocampal, and inferior temporal cortical regions (partial r 5 0.53-0.73). Peak correlations between CSF and PET measures of tau were similar to those between CSF and PET measures of amyloid burden. Finally, we observed significantly higher temporal T807 SUVR in individuals with high amyloid burden.Conclusions: These data support the link between 18 F-T807 PET and CSF measures of tau pathology. In these cognitively normal individuals with 18 F-T807 binding largely restricted to the temporal lobe, 18 F-T807 SUVR in temporal regions appeared more reflective of CSF t-tau and p-tau than a total cortical measure. Neurology ® 2016;87:920-926 GLOSSARY Ab 5 b-amyloid; Ab42 5 b-amyloid 1-42; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; CNE 5 cognitively normal elderly; DVR 5 distribution volume ratio; FLR 5 frontal, parietal, retrosplenial, and lateral temporal cortical regions; HAB 5 Harvard Aging Brain; ITC 5 inferior temporal neocortex; MCI 5 mild cognitive impairment; MGH 5 Massachusetts General Hospital; MMSE 5 Mini-Mental State Examination; MTC 5 middle temporal neocortex; NFT 5 neurofibrillary tangle; p-tau 5 phosphorylated tau; PiB 5 Pittsburgh compound B; ROI 5 region of interest; SUVR 5 standardized uptake value ratio; t-tau 5 total tau.Accumulations of b-amyloid (Ab) and intracellular tau are defining characteristics of Alzheimer disease (AD) pathology. CSF assays of Ab 1-42 (Ab42), total tau (t-tau), and tau phosphorylated at residue 181 (p-tau) proteins are commonly used tools for identifying individuals harboring AD pathology. These CSF-based assays are increasingly being supplemented with imaging biomarkers reflecting molecular pathology in vivo. Following the initial description of 11 C Pittsburgh compound B (PiB), 1 PET-based measures of amyloid pathology have come into increasing use in research and clinical settings. Several groups have demonstrated that PET measures of amyloid burden correlate well with CSF Ab42 measurements, and can be used in concert with other biomarkers as p...

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Section: 21supporting

confidence: 56%

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

et al. 2016

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“…By studying large-scale spatial associations between pathology deposits and GM intensities, we aimed to shed light on the pathogenesis of AD, while offering possible avenues for early detection and monitoring disease treatments. Moreover, there are five limitations in this study: (1) this is a cross-sectional study and, therefore, longitudinal multimodal data including in vivo Tau, A␤, and structural imaging will be essential to confirm and extend the findings reported in this work; (2) we consider our cohort at risk of preclinical AD just by virtue of age; (3) it is important to remark that some individuals of our sample may have primary age-related tauopathy potentially independent of A␤ accumulation (Crary et al, 2014;Jack, 2014;Mungas et al, 2014); (4) all our partial correlation analyses of PET data were done with voxel-level GM intensity correction but not with a partial volume correction approach; and (5) some uptake of our Tau tracer might be located in the choroid plexus. Therefore, findings in the proximity of the choroid plexus should be taken cautiously.…”

Section: Identification Of Specific Brain Regions In Which Pathology mentioning

confidence: 54%

“…More recently, PET techniques sensitive to amyloid deposits have made possible the cross-sectional and longitudinal in vivo analysis of A␤ pathology in humans Sojkova et al, 2011;Villemagne et al, 2011;Vlassenko et al, 2011;Johnson et al, 2012;Schöll et al, 2016). These studies have consistently described early A␤ deposition occurring primarily in heteromodal areas that are associated with AD-specific atrophy (Buckner et al, 2005;Masdeu et al, 2012). Although PET imaging has been able to identify and visualize A␤ deposits for more than a decade , high-affinity radiopharmaceuticals have been successfully developed for Tau only very recently (Maruyama et al, 2013;Chien et al, 2014;Villemagne et al, 2014;.…”

Section: Introductionmentioning

confidence: 99%

“…Volume loss of medial temporal lobe (MTL) structures, e.g., hippocampus, is detectable with magnetic resonance imaging (MRI;Jack et al, 1992;Scheltens et al, 1992;Chetelat and Baron, 2003). More widespread cortical abnormalities, based on structural MRI and positron emission tomography (PET) with fluorodeoxyglucose are detected in heteromodal regions of the frontal, parietal, and temporal lobes (Minoshima et al, 1997;Buckner, 2004;Buckner et al, 2005;Bakkour et al, 2009;Dickerson et al, 2009;Sabuncu et al, 2011) and emphasize the distant dissemination of AD pathologic change. More recently, PET techniques sensitive to amyloid deposits have made possible the cross-sectional and longitudinal in vivo analysis of A␤ pathology in humans Sojkova et al, 2011;Villemagne et al, 2011;Vlassenko et al, 2011;Johnson et al, 2012;Schöll et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain

Sepulcre

Schultz

Sabuncu

et al. 2016

Journal of Neuroscience

165

170

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We provide a comparative in vivo examination of the brain network-based distribution of two hallmarks of Alzheimer's disease (AD) pathology in cognitively normal individuals: (1) Tau, detected with a novel positron emission tomography (PET) tracer known as 18 F-AV-1451; and (2) amyloid-␤, quantified with 11 C-PiB PET. We used a high-resolution graph-based approach to investigate local-tolocal and local-to-distributed cortical associations between the maps of Tau, amyloid-␤, and gray matter intensity. Our study shows that Tau and amyloid-␤ deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, Tau and amyloid-␤ accumulations have strong network interdigitations in heteromodal and associative areas of the cortical mantle, particularly the inferior-lateral temporal lobe. These findings contribute significantly to our understanding of how these two main hallmarks of AD pathology propagate across the elderly human brain.

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“…This composite includes measures of general cognition (MMSE) and speeded executive function (DSC), but is 50% composed of episodic memory tests (13). All tests were z-transformed using the mean and standard deviation of performance by clinically normal older adults (n=256, age range: 61–90) years) participating in the Harvard Aging Brain Study (24, 25). This population served as an ideal normative sample by which to classify our current pilot sample as individuals were recruited from the same geographic area and recruited through the same centers.…”

Section: Methodsmentioning

confidence: 99%

Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the Nih Toolbox and Cogstate C3 Batteries

Buckley¹,

Sparks²,

Papp³

et al. 2017

J Prev Alz Dis

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Background: As prevention trials for Alzheimer’s disease move into asymptomatic populations, identifying older individuals who manifest the earliest cognitive signs of Alzheimer’s disease is critical. Computerized cognitive testing has the potential to replace current gold standard paper and pencil measures and may be a more efficient means of assessing cognition. However, more empirical evidence about the comparability of novel computerized batteries to paper and pencil measures is required. Objectives: To determine whether two computerized IPad batteries, the NIH Toolbox Cognition Battery and Cogstate-C3, similarly predict subtle cognitive impairment identified using the Preclinical Alzheimer Cognitive Composite (PACC). Design, Setting, Participants: A pilot sample of 50 clinically normal older adults (Mage=68.5 years±7.6, 45% non-Caucasian) completed the PACC assessment, and the NIH Toolbox and Cogstate-C3 at research centers of Massachusetts General and Brigham and Women’s Hospitals. Participants made 3-4 in-clinic visits, receiving the PACC first, then the NIH Toolbox, and finally the Cogstate-C3. Measurements: Performance on the PACC was dichotomized by typical performance (>= 0.5SD), versus subtle cognitive impairment (<0.5SD). Composites for each computerized battery were created using principle components analysis, and compared with the PACC using non-parametric Spearman correlations. Logistic regression analyses were used to determine which composite was best able to classify subtle cognitive impairment from typical performance. Results: The NIH Toolbox formed one composite and exhibited the strongest within-battery alignment, while the Cogstate-C3 formed two distinct composites (Learning-Memory and Processing Speed-Attention). The NIH Toolbox and C3 Learning-Memory composites exhibited positive correlations with the PACC (ρ=0.49, p<0.001; ρ=0.58, p<0.001, respectively), but not the C3 Processing Speed-Attention composite, ρ=-0.18, p=0.22. The C3 Learning-Memory was the only composite that classified subtle cognitive impairment, and demonstrated the greatest sensitivity (62%) and specificity (81%) for that subtle cognitive impairment. Conclusions: Preliminary findings suggest that the NIH Toolbox has the advantage of showing the strongest overall clustering and alignment with standardized paper-and-pencil tasks. By contrast, Learning-Memory tasks within the Cogstate-C3 battery have the greatest potential to identify cross-sectional, subtle cognitive impairment as defined by the PACC.

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Harvard Aging Brain Study: Dataset and accessibility

Cited by 154 publications

References 18 publications

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain

Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the Nih Toolbox and Cogstate C3 Batteries

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