Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults

A4 Study team, full listing of team and site personnel available at A4STUDΥ.org

doi:https://doi.org/10.14283/jpad.2022.58

Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults

A4 Study team, full listing of team and site personnel available at A4STUDΥ.org

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

Abstract

Background
Performance of cognitively complex “instrumental activities of daily living” (IADL) has previously been related to amyloid deposition in preclinical Alzheimer’s disease.

Objectives
We aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults.

Design
Cross-sectional.

Setting
Data was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.

Participants
Participants (n = 447, age 71.9+4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies.

Measurements
IADL performance was measured using the self- and study partner-reported versions of the Alzheimer’s Disease Cooperative Study Activities of Daily Living — Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included.

Results
Participants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002).

Discussion
We found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.

Original language	English
Pages (from-to)	801-808
Number of pages	8
Journal	The Journal of Prevention of Alzheimer’s Disease
Volume	9
Issue number	4
Early online date	16 Jun 2022
DOIs	https://doi.org/10.14283/jpad.2022.58
Publication status	Published - Oct 2022

Keywords

Alzheimer’s disease
cognitively normal
flortaucipir
instrumental activities of daily living
positron emission tomography
tau

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.14283/jpad.2022.58

https://research.vu.nl/ws/files/213758271/Everyday_Functioning_and_Entorhinal_and_Inferior_Temporal_Tau_Burden_in_Cognitively_Normal_Older_Adults.pdfLicence: Article 25fa Dutch Copyright Act

Cite this

@article{8a758587196c4e7ebbe1d2c2d30f278e,

title = "Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults",

abstract = "BackgroundPerformance of cognitively complex “instrumental activities of daily living” (IADL) has previously been related to amyloid deposition in preclinical Alzheimer{\textquoteright}s disease.ObjectivesWe aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults.DesignCross-sectional.SettingData was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer{\textquoteright}s (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.ParticipantsParticipants (n = 447, age 71.9+4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies.MeasurementsIADL performance was measured using the self- and study partner-reported versions of the Alzheimer{\textquoteright}s Disease Cooperative Study Activities of Daily Living — Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included.ResultsParticipants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002).DiscussionWe found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.",

keywords = "Alzheimer{\textquoteright}s disease, cognitively normal, flortaucipir, instrumental activities of daily living, positron emission tomography, tau",

author = "{A4 Study team, full listing of team and site personnel available at A4STUDΥ.org} and Dubbelman, {M. A.} and J. Sanchez and Schultz, {A. P.} and Rentz, {D. M.} and Amariglio, {R. E.} and Sikkes, {S. A.M.} and Sperling, {R. A.} and Johnson, {K. A.} and Marshall, {Gad A.}",

note = "Funding Information: The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women{\textquoteright}s Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer{\textquoteright}s Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data to advance the quest to find a successful treatment for Alzheimer{\textquoteright}s disease. We would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available at a4study.org/a4-studyteam. Funding Information: Conflicts of interest/Disclosures: MAD and JSS have nothing to disclose. APS has consulted for Janssen, Biogen, Qynapse, and NervGen. DMR has served as a consultant for Eli Lilly, Biogen Idec, Digital Cognition Technologies, and serves as a member of the Scientific Advisory Board for Neurotrack. REA has nothing to disclose. SAMS has provided consultancy services in the past 2 years for Nutricia and Takeda, and has received license fees from Green Valley, VtV Therapeutics, Alzheon, Vivoryon and Roche, as well as honoraria from Boehringer and Toyama. All funds were paid to her institution. RAS has served as a paid consultant for AC Immune, Alynlam, Cytox, Genentech, Janssen, Neurocentria, Prothena, and Roche. She has received research support as an investigator for Eli Lilly, Janssen and Eisai Alzheimer disease clinical trials. KAJ has served as paid consultant for Bayer, GE Healthcare, Janssen Alzheimer{\textquoteright}s Immunotherapy, Siemens Medical Solutions, Genzyme, Novartis, Biogen, Roche, ISIS Pharma, AZTherapy, GEHC, Lundberg, and Abbvie. He is a site coinvestigator for Eli Lilly/Avid, Pfizer, Janssen Immunotherapy, and Navidea. He has spoken at symposia sponsored by Janssen Alzheimer{\textquoteright}s Immunotherapy and Pfizer. GAM has received research salary support for serving as site principal investigator for clinical trials funded by Eisai Inc., Eli Lilly and Company, and Genentech. These relationships are not related to the content in the manuscript. Funding Information: Funding: The A4 Study is a secondary prevention trial in preclinical Alzheimer{\textquoteright}s disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging (U19AG010483; R01AG063689), Eli Lilly and Company, Alzheimer{\textquoteright}s Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid, Cogstate, Albert Einstein College of Medicine, US Against Alzheimer{\textquoteright}s disease, and Foundation for Neurologic Diseases. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer{\textquoteright}s Association and GHR Foundation. MAD is supported by grants from Alzheimer Nederland and the Amsterdam UMC Young Talent Fund. SAMS was funded by public-private funding from Health&Holland, Topsector Life Sciences & Health (PPPallowance; LSHM20084-SGF, project DEFEAT-AD, LSHM19051, project OTAPA), and the National Institutes of Health. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript. Publisher Copyright: {\textcopyright} 2022, Serdi.",

year = "2022",

month = oct,

doi = "https://doi.org/10.14283/jpad.2022.58",

language = "English",

volume = "9",

pages = "801--808",

journal = "The Journal of Prevention of Alzheimer{\textquoteright}s Disease",

issn = "2274-5807",

publisher = "Springer International Publishing AG",

number = "4",

}

TY - JOUR

T1 - Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults

AU - A4 Study team, full listing of team and site personnel available at A4STUDΥ.org

AU - Dubbelman, M. A.

AU - Sanchez, J.

AU - Schultz, A. P.

AU - Rentz, D. M.

AU - Amariglio, R. E.

AU - Sikkes, S. A.M.

AU - Sperling, R. A.

AU - Johnson, K. A.

AU - Marshall, Gad A.

N1 - Funding Information: The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women’s Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer’s Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data to advance the quest to find a successful treatment for Alzheimer’s disease. We would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available at a4study.org/a4-studyteam. Funding Information: Conflicts of interest/Disclosures: MAD and JSS have nothing to disclose. APS has consulted for Janssen, Biogen, Qynapse, and NervGen. DMR has served as a consultant for Eli Lilly, Biogen Idec, Digital Cognition Technologies, and serves as a member of the Scientific Advisory Board for Neurotrack. REA has nothing to disclose. SAMS has provided consultancy services in the past 2 years for Nutricia and Takeda, and has received license fees from Green Valley, VtV Therapeutics, Alzheon, Vivoryon and Roche, as well as honoraria from Boehringer and Toyama. All funds were paid to her institution. RAS has served as a paid consultant for AC Immune, Alynlam, Cytox, Genentech, Janssen, Neurocentria, Prothena, and Roche. She has received research support as an investigator for Eli Lilly, Janssen and Eisai Alzheimer disease clinical trials. KAJ has served as paid consultant for Bayer, GE Healthcare, Janssen Alzheimer’s Immunotherapy, Siemens Medical Solutions, Genzyme, Novartis, Biogen, Roche, ISIS Pharma, AZTherapy, GEHC, Lundberg, and Abbvie. He is a site coinvestigator for Eli Lilly/Avid, Pfizer, Janssen Immunotherapy, and Navidea. He has spoken at symposia sponsored by Janssen Alzheimer’s Immunotherapy and Pfizer. GAM has received research salary support for serving as site principal investigator for clinical trials funded by Eisai Inc., Eli Lilly and Company, and Genentech. These relationships are not related to the content in the manuscript. Funding Information: Funding: The A4 Study is a secondary prevention trial in preclinical Alzheimer’s disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging (U19AG010483; R01AG063689), Eli Lilly and Company, Alzheimer’s Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid, Cogstate, Albert Einstein College of Medicine, US Against Alzheimer’s disease, and Foundation for Neurologic Diseases. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer’s Association and GHR Foundation. MAD is supported by grants from Alzheimer Nederland and the Amsterdam UMC Young Talent Fund. SAMS was funded by public-private funding from Health&Holland, Topsector Life Sciences & Health (PPPallowance; LSHM20084-SGF, project DEFEAT-AD, LSHM19051, project OTAPA), and the National Institutes of Health. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript. Publisher Copyright: © 2022, Serdi.

PY - 2022/10

Y1 - 2022/10

N2 - BackgroundPerformance of cognitively complex “instrumental activities of daily living” (IADL) has previously been related to amyloid deposition in preclinical Alzheimer’s disease.ObjectivesWe aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults.DesignCross-sectional.SettingData was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.ParticipantsParticipants (n = 447, age 71.9+4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies.MeasurementsIADL performance was measured using the self- and study partner-reported versions of the Alzheimer’s Disease Cooperative Study Activities of Daily Living — Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included.ResultsParticipants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002).DiscussionWe found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.

AB - BackgroundPerformance of cognitively complex “instrumental activities of daily living” (IADL) has previously been related to amyloid deposition in preclinical Alzheimer’s disease.ObjectivesWe aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults.DesignCross-sectional.SettingData was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.ParticipantsParticipants (n = 447, age 71.9+4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies.MeasurementsIADL performance was measured using the self- and study partner-reported versions of the Alzheimer’s Disease Cooperative Study Activities of Daily Living — Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included.ResultsParticipants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002).DiscussionWe found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.

KW - Alzheimer’s disease

KW - cognitively normal

KW - flortaucipir

KW - instrumental activities of daily living

KW - positron emission tomography

KW - tau

UR - http://www.scopus.com/inward/record.url?scp=85133847987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85133847987&partnerID=8YFLogxK

U2 - https://doi.org/10.14283/jpad.2022.58

DO - https://doi.org/10.14283/jpad.2022.58

M3 - Article

C2 - 36281685

SN - 2274-5807

VL - 9

SP - 801

EP - 808

JO - The Journal of Prevention of Alzheimer’s Disease

JF - The Journal of Prevention of Alzheimer’s Disease

IS - 4

ER -

Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults

Abstract

Keywords

UN SDGs

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