ArticleNeurology2022
Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.
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Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43citing papers in PubMed
9.4field-weighted citation impact, top 1% of its field
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Theoretical and practical challenges for capturing reserve and resilience in aging and Alzheimer's disease: A narrative review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Digital maze test reveals cognitive performance patterns associated with amyloid-β and tau.Neuropsychology · 2026Article
- Amyloid spatial extent with florbetapir-PET for early detection of preclinical Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Article
- Classifying cognitive status with TabCAT Match and UDS executive function tests.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Characterizing amyloid and tau positron emission tomography-based stages across the clinical continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Living Alone, Early Tau Pathology, and Loneliness in Cognitively Unimpaired Older Adults During the COVID-19 Pandemic.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026Article
- Longitudinal biomarker studies in human neuroimaging: capturing biological change of Alzheimer's pathology.Alzheimer's research & therapy · 2025Review
- Lower locus coeruleus integrity is associated with diminished practice effects in clinically unimpaired older individuals.Neurobiology of aging · 2025Article
- Modifiable risk factor profiles moderate the effect of β-amyloid pathology on cognition in aging.Neurobiology of aging · 2025Article
- Cognitive variation reflects amyloid, tau, and neurodegenerative biomarkers in Alzheimer's disease.GeroScience · 2025Article
- Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm.NPJ digital medicine · 2025Article
- Association of precuneus Aβ burden with default mode network function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Coconut oil derived medium-chain triglycerides ameliorated memory deficits via promoting neurite outgrowth and maintaining gut homeostasis in 5×FAD mice.Frontiers in nutrition · 2025Article
- Multimodal neuroimaging biomarkers and subtle cognitive decline in a population-based cohort without dementia.Journal of Alzheimer's disease : JAD · 2025Article
- Longitudinal relationships between Aβ and tau to executive function and memory in cognitively normal older adults.Neurobiology of aging · 2025Article
- Neurochemical organization of cortical proteinopathy and neurophysiology along the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Associations of cerebral amyloid beta and tau with cognition from midlife.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis.Scientific reports · 2024Article
- Spatial extent as a sensitive amyloid-PET metric in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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Authors and funding
11 authors at 1 institution in 1 country.
Michelle E FarrellFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Kathryn V PappFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Rachel F BuckleyFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0002-5356-5537
Heidi I L JacobsFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Aaron P SchultzFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Michael J ProperziFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Patrizia VanniniFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Bernard J HanseeuwFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Dorene M RentzFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0002-6318-9213
Keith A JohnsonFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Reisa A SperlingFrom the Departments of Neurology (M.E.F., K.V.P., R.F.B., A.P.S., M.J.P., P.V., D.R.M., R.A.S.) and Radiology (H.I.L.J., B.J.H., K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (K.V.P., R.F.B., P.V., D.M.R., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Florey Institute of Neuroscience and Mental Health (R.F.B.); Melbourne School of Psychological Sciences (R.F.B.), University of Melbourne, Australia; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, the Netherlands; and Cliniques Universitaires Saint-Luc (B.J.H.), Université Catholique de Louvain, Brussels, Belgium.
Jisc · GB
Funding
Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley · 2010 to 2026
$50.2MTHE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI FROSCH, MATTHEW P · 1985 to 2018
$42.1MProject 4P41EB015896 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2018
$9.8MA Storage Area Network for Structural and Functional Image AnalysisS10RR023401 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE · 2009 to 2009
$2.0MSILICON GRAPHICS PRISM EXTREME 128P/1TBS10RR023043 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI SORENSEN, ALMA GREGORY · 2006 to 2006
$1.5MMentoring Imaging Research in Early ADK24AG035007 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SPERLING, REISA A. · 2010 to 2020
$1.4MA Siemens MAGNETOTOM Trio 3 Tesla MRI SystemS10RR021110 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2006 to 2006
$500kNCRR NIH HHS S10 RR021110NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS K24 AG035007NIA NIH HHS P01 AG036694NIA NIH HHS P50 AG005134NIBIB NIH HHS P41 EB015896
Abstract
BACKGROUND AND
objectivesAlzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology.
methodsOne hundred twelve clinically normal adults with longitudinal Pittsburgh compound B (PiB)-PET,
resultsSteeper PiB slopes were associated with declining processing speed (Digit Symbol Substitution Test [DSST], Trail Making Test Part A) in those <CL20 and expanded to include learning/memory retrieval (FCSRT-FR], Selective Reminding Test Total Recall [SRT-tr], Logical Memory Immediate Recall) in the <CL40 group. FTP had limited effects under CL20, with only rising right IT FTP slope related to declining FCSRT-FR and SRT-tr learning/memory retrieval. When we expanded to include those initially <CL40, rising FTP level or slope was related to declines across all tasks, and PiB slope effects on memory retrieval but not DSST score were reduced. A composite measure of processing speed and memory retrieval tasks provided the strongest prediction of decline under CL40, while PACC score remained optimal at high levels of Aβ (>CL40). DISCUSSION: Early, Aβ-mediated cognitive slowing was detected for processing speed measures, while early memory retrieval declines were associated with emerging Aβ and tau pathology. Composites of these measures may help determine whether anti-Aβ or anti-tau therapies administered at the first signs of pathology might preserve cognitive function. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in clinically normal older adults, emerging PET-detected AD pathology is associated with declining processing speeds and memory retrieval.
Indexed as
Alzheimer DiseaseCognitive DysfunctionAgedAmyloid beta-PeptidesBrainCognitionHumansPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesMAPT protein, humantau Proteins
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