Reisa A Sperling

Harvard Medical School, Boston, Massachusetts, United States

Are you Reisa A Sperling?

Claim your profile

Publications (259)2402.35 Total impact

  • American Journal of Geriatric Psychiatry 03/2015; 23(3):S96-S97. · 3.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.
    Expert Review of Neurotherapeutics 03/2015; 15(3):327-33. · 2.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several large-scale Alzheimer disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. Longitudinal study from February 2002 through February 2007 at participating Alzheimer's Disease Cooperative Study sites. Individuals were followed up annually for 48 months after the baseline visit. The study included 468 healthy older individuals (Clinical Dementia Rating scale [CDR] global scores of 0, above cutoff on the modified Mini-Mental State Examination and Free and Cued Selective Reminding Test) (mean [SD] age, 79.4 [3.6] years; age range, 75.0-93.8 years). All study participants and their study partners completed the self and partner CFIs annually. Individuals also underwent concurrent annual neuropsychological assessment and APOE genotyping. The CFI scores between clinical progressors (CDR score, ≥0.5) and nonprogressors (CDR score, 0) and between APOE ε4 carriers and noncarriers were compared. Correlations of change between the CFI scores and neuropsychological performance were assessed longitudinally. At 48 months, group differences between clinical progressors and non-progressors were significant for self (2.13, SE=0.45, P < .001), partner (5.08, SE=0.59, P < .001), and self plus partner (7.04, SE=0.83, P < .001) CFI total scores. At month 48, APOE ε4 carriers had greater progression than noncarriers on the partner (1.10, SE=0.44, P < .012) and self plus partner (1.56, SE=0.63, P < .014) CFI scores. Both self and partner CFI change were associated with longitudinal cognitive decline (self, ρ=0.32, 95% CI, 0.13 to 0.46; partner, ρ=0.56, 95% CI, 0.42 to 0.68), although findings suggest self-report may be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. Demonstrating long-term clinical benefit will be critical for the success of recently launched secondary prevention trials. The CFI appears to be a brief, but informative potential outcome measure that provides insight into functional abilities at the earliest stages of disease.
    JAMA Neurology 02/2015; · 7.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral 18F-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS >10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, gender, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia, and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p = 0.03) was significantly associated with lower HV and was marginally related (p = 0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p = 0.02) and Apathy-Anhedonia (p = 0.05) were related to lower HV while higher Apathy-Anhedonia (p = 0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden.
    Journal of Alzheimer's disease: JAD 02/2015; · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Willem Huijbers1,2, Elizabeth C. Mormino1,3, Aaron P. Schultz3, Sarah Wigman1,2, Andrew M. Ward1,2,4, Mykol Larvie2,3, Rebecca E. Amariglio1,2, Gad A. Marshall1,2, Dorene M. Rentz1,2, Keith A. Johnson2,3 and Reisa A. Sperling1,2,31 Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham and Womentextquoterights Hospital, Harvard Medical School, Boston, MA, USA2 Athinoula A. Martinos Centre for Biomedical Imaging, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA3 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA4 Helen Willis Neuroscience Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USACorrespondence to: Willem Huijbers, Martinos Centre for Biomedical Imaging, 149 13th Street, Charlestown MA 02129 E-mail: w.huijbersatgmail.comReceived August 5, 2014.Revision received November 2, 2014.Accepted November 22, 2014.Summary Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activitytextemdashconsistent with findings in genetic at-risk populationstextemdashand other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimertextquoterights disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model, amyloid-β status, hippocampal activation, and hippocampal volume independently predicted clinical progression. These results indicate that amyloid-β positive patients with mild cognitive impairment are more likely on a path towards Alzheimertextquoterights disease dementia than amyloid-β negative patients. Increased hippocampal activity is discussed in relation to neuronal compensation and/or amyloid-β induced excitoxicity. amyloid depositionMCIhippocampal activationfunctional MRIclinical progressionAbbreviationsDVRdistribution volume ratioMCImild cognitive impairmentPiBPittsburg compound-Btextcopyright The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com
    Brain 02/2015; · 10.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Apathy is a common neuropsychiatric symptom in Alzheimer's disease dementia and amnestic mild cognitive impairment and is associated with cortical atrophy in Alzheimer's disease dementia. This study investigated possible correlations between apathy and cortical atrophy in 47 individuals with mild cognitive impairment and 19 clinically normal elderly. Backward elimination multivariate linear regression was used to evaluate the cross-sectional relationship between scores on the Apathy Evaluation Scale and thickness of several cortical regions and covariates. Lower inferior temporal cortical thickness was predictive of greater apathy. Greater anterior cingulate cortical thickness was also predictive of greater apathy, suggesting an underlying reactive process.
    The Journal of neuropsychiatry and clinical neurosciences 01/2015; 27(1):e22-7. · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is acknowledged that progress in combined therapeutic approaches for Alzheimer's disease (AD) will require an unprecedented level of collaboration. At a meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition and the Critical Path Institute, investigators from industry, academia and regulatory agencies agreed on the need for combinatorial approaches to treating AD. The need for advancing multiple targets includes recognition for novel adaptive trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination. A combination trial now being planned may test drugs targeting different pathogenic pathways or multiple targets along a common pathway. Collaborations and consortia-based strategies are pivotal for success and a regulatory framework is recommended for success.
    Expert Review of Neurotherapeutics 12/2014; 15(1):1-7. · 2.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition. Copyright © 2014. Published by Elsevier Inc.
    NeuroImage 12/2014; 107. · 6.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Genome-wide association studies (GWAS) have linked variants in TREM2 and TREML2 with Alzheimer's disease (AD) and AD endophenotypes. Here, we pursue a targeted analysis of the TREM locus in relation to cognitive decline and pathological features of AD.Methods: Clinical, cognitive, and neuropathological phenotypes were collected in three prospective cohorts on aging (n=3421 subjects). Our primary analysis was an association with neuritic plaque pathology. To functionally characterize the associated variants, we used flow cytometry data to measure TREM1 expression on monocytes.Results: We provide evidence that an intronic variant, rs6910730G, in Triggering Receptor Expressed on Myeloid cells 1 (TREM1), is associated with an increased burden of neuritic plaques (p=3.7x10-4), diffuse plaques (p=4.1x10-3), and Aβ density (p=2.6x10-3) as well as an increased rate of cognitive decline (p=5.3x10-3). A variant upstream of TREM2, rs7759295C, is independently associated with an increased Tau tangle density (p=4.9x10-4), an increased burden of neurofibrillary tangles (p=9.1x10-3), and an increased rate of cognitive decline (p=2.3x10-3). Finally, a cytometric analysis shows that the TREM1 rs6910730G allele is associated with decreased TREM1 expression on the surface of myeloid cells (p=1.7x10-3).Interpretation: We provide evidence that two common variants within the TREM locus are associated with pathological features of AD and aging-related cognitive decline. Our evidence suggests that these variants are likely to be independent of known AD variants and that they may work through an alteration of myeloid cell function. This article is protected by copyright. All rights reserved.
    Annals of Neurology 12/2014; · 11.91 Impact Factor
  • Reisa Sperling, Elizabeth Mormino, Keith Johnson
    [Show abstract] [Hide abstract]
    ABSTRACT: As the field begins to test the concept of a “preclinical” stage of neurodegenerative disease, when the pathophysiological process has begun in the brain, but clinical symptoms are not yet manifest, a number of intriguing questions have already arisen. In particular, in preclinical Alzheimer’s disease (AD), the temporal relationship of amyloid markers to markers of neurodegeneration and their relative utility in the prediction of cognitive decline among clinically normal older individuals remains to be fully elucidated. Secondary prevention trials in AD have already begun in both genetic at-risk and amyloid at-risk cohorts, with several more trials in the planning stages, and should provide critical answers about whether intervention at this very early stage of disease can truly bend the curve of clinical progression. This review will highlight recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical AD, and the remaining gaps in knowledge.
    Neuron 11/2014; 84(3). · 15.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.
    Cerebral Cortex 10/2014; · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025. To guide investments, activities, and the measurement of progress toward achieving this 2025 goal, in its first annual plan update (2013) HHS also incorporated into the plan a set of short, medium and long-term milestones. HHS further committed to updating these milestones on an ongoing basis to account for progress and setbacks, and emerging opportunities and obstacles. To assist HHS as it updates these milestones, the Alzheimer's Association convened a National Plan Milestone Workgroup consisting of scientific experts representing all areas of Alzheimer's and dementia research. The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's by 2025. This report presents these Workgroup recommendations.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 10/2014; 10(5 Suppl):S430-52. · 14.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Subjective cognitive concerns may represent a simple method to assess likelihood of memory decline among apolipoprotein E (APOE) ε4 carriers. Methods We examined the relationship of self-reported subjective cognitive concerns, using seven specific cognitive concerns, with memory and memory decline over 6 years among APOE ε4 carriers and non-carriers from the Nurses' Health Study. Results In both groups, increasing subjective cognitive concern score predicted worse baseline memory and faster rates of subsequent memory decline, after adjustment for age, education and depression. The relation with baseline memory appeared statistically stronger in APOE ε4 carriers (P-interaction = 0.03). For memory decline, mean differences in slopes of episodic memory (95% CI) for 4 to 7 versus no concern = −0.05 (−0.10, 0.01) standard units in APOE ε4 carriers, and −0.04 (−0.08, −0.01) standard units in non-carriers. Conclusions APOE ε4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline.
    Alzheimer's and Dementia 09/2014; · 17.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Assessing the ability of Alzheimer disease neuroimaging markers to predict short-term cognitive decline among clinically normal (CN) individuals is critical for upcoming secondary prevention trials using cognitive outcomes.
    JAMA Neurology 09/2014; · 7.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activities of daily living (ADL) impairment is a hallmark of Alzheimer's disease (AD) dementia, but impairment in instrumental ADL (IADL) has been reported in mild cognitive impairment (MCI). The Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center (MADRC)-Informant Report (SIST-MIR) includes 60 graded items that assist in scoring the Clinical Dementia Rating; it assesses the spectrum of cognitive and ADL changes relevant to early AD. Of the 60 SIST-M-IR items, 41 address IADL; we aimed to determine which of these best discriminate individuals with MCI from clinically normal (CN) elderly.
    Current Alzheimer Research 09/2014; 11(8):785-91. · 3.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Functional connectivity magnetic resonance imaging (fcMRI) is a powerful tool for understanding the network level organization of the brain in research settings and is increasingly being used to study large-scale neuronal network degeneration in clinical trial settings. Presently, a variety of techniques, including seed-based correlation analysis and group independent components analysis (with either dual regression or back projection) are commonly employed to compute functional connectivity metrics. In the present report, we introduce template based rotation,(1) a novel analytic approach optimized for use with a priori network parcellations, which may be particularly useful in clinical trial settings. Template based rotation was designed to leverage the stable spatial patterns of intrinsic connectivity derived from out-of-sample datasets by mapping data from novel sessions onto the previously defined a priori templates. We first demonstrate the feasibility of using previously defined a priori templates in connectivity analyses, and then compare the performance of template based rotation to seed based and dual regression methods by applying these analytic approaches to an fMRI dataset of normal young and elderly subjects. We observed that template based rotation and dual regression are approximately equivalent in detecting fcMRI differences between young and old subjects, demonstrating similar effect sizes for group differences and similar reliability metrics across 12 cortical networks. Both template based rotation and dual-regression demonstrated larger effect sizes and comparable reliabilities as compared to seed based correlation analysis, though all three methods yielded similar patterns of network differences. When performing inter-network and sub-network connectivity analyses, we observed that template based rotation offered greater flexibility, larger group differences, and more stable connectivity estimates as compared to dual regression and seed based analyses. This flexibility owes to the reduced spatial and temporal orthogonality constraints of template based rotation as compared to dual regression. These results suggest that template based rotation can provide a useful alternative to existing fcMRI analytic methods, particularly in clinical trial settings where predefined outcome measures and conserved network descriptions across groups are at a premium.
    NeuroImage 08/2014; · 6.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile.
    JAMA Neurology 07/2014; · 7.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Advanced aging negatively impacts memory performance. Brain aging has been associated with shrinkage in medial temporal lobe structures essential for memory-including hippocampus and entorhinal cortex-and with deficits in default-mode network connectivity. Yet, whether and how these imaging markers are relevant to age-related memory deficits remains a topic of debate. Using a sample of 182 older (age 74.6 ± 6.2 years) and 66 young (age 22.2 ± 3.6 years) participants, this study examined relationships among memory performance, hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity across aging. All imaging markers and memory were significantly different between young and older groups. Each imaging marker significantly mediated the relationship between age and memory performance and collectively accounted for most of the variance in age-related memory performance. Within older participants, default-mode connectivity and hippocampus volume were independently associated with memory. Structural equation modeling of cross-sectional data within older participants suggest that entorhinal thinning may occur before reduced default-mode connectivity and hippocampal volume loss, which in turn lead to deficits in memory performance.
    Neurobiology of Aging 07/2014; · 4.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD.METHODS: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study.RESULTS: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r(2) > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.CONCLUSIONS: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
    Neurology 06/2014; · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes. OBJECTIVE To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evidence of AD pathology using the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess episodic memory, timed executive function, and global cognition. The ADCS-PACC is the primary outcome measure for the first clinical trial in preclinical AD (ie, the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study). DESIGN, SETTING, AND PARTICIPANTS With the ADCS-PACC, we derive pilot estimates of amyloid-related decline using data from 2 observational studies conducted in North America and another conducted in Australia. The participants analyzed had normal cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies. MAIN OUTCOMES AND MEASURES For the 2 studies that collected data on Aβ levels (ADNI and AIBL), we estimate decline in a preclinical AD "Aβ-positive" placebo group and compare them with an "Aβ-negative" group. For the study that did not include data on Aβ levels (the ADCS Prevention Instrument [ADCS-PI] study), we grouped participants by the presence of APOE-ε4 and by clinical progression. RESULTS In ADNI, Aβ-positive participants showed more decline than did Aβ-negative participants with regard to the ADCS-PACC score at 24 months (mean [SE] difference, -1.239 [0.522] [95% CI, -2.263 to -0.215]; P = .02). In AIBL, the mean (SE) difference is significant at both 18 months (-1.009 [0.406] [95% CI, -1.805 to -0.213]; P = .01) and 36 months (-1.404 [0.452] [95% CI, -2.290 to -0.519]; P = .002). In the ADCS-PI study, APOE-ε4 allele carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE] score, -0.742 [0.294] [95% CI, -1.318 to -0.165]; P = .01) and 36 months (-1.531 [0.469] [95% CI, -2.450 to -0.612]; P = .001). In the ADCS-PI study, cognitively normal participants who progress from a global Clinical Dementia Rating score of 0 are significantly worse on the ADCS-PACC than cognitively normal participants who are stable with a global Clinical Dementia Rating score of 0 at months 12, 24, and 36 (mean [SE] ADCS-PACC score, -4.471 [0.702] [95% CI, -5.848 to -3.094]; P < .001). Using pilot estimates of variance and assuming 500 participants per group with 30% attrition and a 5% α level, we project 80% power to detect effects in the range of Δ = 0.467 to 0.733 on the ADCS-PACC. CONCLUSIONS AND RELEVANCE Analyses of at-risk cognitively normal populations suggest that we can reliably measure the first signs of cognitive decline with the ADCS-PACC. These analyses also suggest the feasibility of secondary prevention trials.
    JAMA Neurology 06/2014; · 7.01 Impact Factor

Publication Stats

9k Citations
2,402.35 Total Impact Points

Institutions

  • 2002–2015
    • Harvard Medical School
      • Department of Neurology
      Boston, Massachusetts, United States
  • 2013
    • Alzheimer's Association
      Chicago, Illinois, United States
    • University of California, San Diego
      • Department of Neurosciences
      San Diego, CA, United States
  • 2002–2013
    • Massachusetts General Hospital
      • • Athinoula A. Martinos Center for Biomedical Imaging
      • • Department of Neurology
      • • Alzheimer Research Unit
      Boston, Massachusetts, United States
  • 2012
    • Boston University
      • Department of Psychology
      Pittsburgh, PA, United States
  • 2001–2012
    • Harvard University
      • Department of Psychology
      Cambridge, Massachusetts, United States
    • Brigham and Women's Hospital
      • • Department of Neurology
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2011
    • Banner Alzheimer's Institute
      Phoenix, Arizona, United States
    • Partners HealthCare
      • Department of Neurology
      Boston, MA, United States
  • 2010
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2006
    • Johns Hopkins University
      Baltimore, Maryland, United States