Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden
IMPORTANCE: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD...
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| creator | Buckley, Rachel F Hanseeuw, Bernard Schultz, Aaron P Vannini, Patrizia Aghjayan, Sarah L Properzi, Michael J Jackson, Jonathan D Mormino, Elizabeth C Rentz, Dorene M Sperling, Reisa A Johnson, Keith A Amariglio, Rebecca E |
| description | IMPORTANCE: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. OBJECTIVE: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. DESIGN, SETTING, AND PARTICIPANTS: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11–labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. MAIN OUTCOMES AND MEASURES: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. RESULTS: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P |
| doi_str_mv | 10.1001/jamaneurol.2017.2216 |
| format | Article |
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OBJECTIVE: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. DESIGN, SETTING, AND PARTICIPANTS: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11–labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. MAIN OUTCOMES AND MEASURES: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. RESULTS: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 0.10; 95% CI, −0.08 to 0.28; P = .27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = −0.36; 95% CI, −0.34 to 0.09; P = .25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. CONCLUSIONS AND RELEVANCE: Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2017.2216</identifier><identifier>PMID: 28973551</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Aged ; Aged, 80 and over ; Amyloid beta-Peptides - metabolism ; Brain - diagnostic imaging ; Brain - metabolism ; Carbolines ; Cognitive Dysfunction - diagnostic imaging ; Cognitive Dysfunction - metabolism ; Cross-Sectional Studies ; Diagnostic Self Evaluation ; Entorhinal Cortex - diagnostic imaging ; Entorhinal Cortex - metabolism ; Female ; Frontal Lobe - diagnostic imaging ; Frontal Lobe - metabolism ; Humans ; Male ; Middle Aged ; Neocortex - diagnostic imaging ; Neocortex - metabolism ; Parietal Lobe - diagnostic imaging ; Parietal Lobe - metabolism ; Phenanthrolines ; Positron-Emission Tomography ; Radiopharmaceuticals ; Surveys and Questionnaires ; tau Proteins - metabolism ; Tauopathies - diagnostic imaging ; Tauopathies - metabolism ; Temporal Lobe - diagnostic imaging ; Temporal Lobe - metabolism</subject><ispartof>JAMA neurology, 2017-12, Vol.74 (12), p.1455-1463</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a427t-1254be93f4b35a15a912c8075f86b2f5b993b36687b6dcd900bcf6f6897a72f03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2017.2216$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2017.2216$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,776,780,881,3326,27903,27904,76236,76239</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28973551$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buckley, Rachel F</creatorcontrib><creatorcontrib>Hanseeuw, Bernard</creatorcontrib><creatorcontrib>Schultz, Aaron P</creatorcontrib><creatorcontrib>Vannini, Patrizia</creatorcontrib><creatorcontrib>Aghjayan, Sarah L</creatorcontrib><creatorcontrib>Properzi, Michael J</creatorcontrib><creatorcontrib>Jackson, Jonathan D</creatorcontrib><creatorcontrib>Mormino, Elizabeth C</creatorcontrib><creatorcontrib>Rentz, Dorene M</creatorcontrib><creatorcontrib>Sperling, Reisa A</creatorcontrib><creatorcontrib>Johnson, Keith A</creatorcontrib><creatorcontrib>Amariglio, Rebecca E</creatorcontrib><title>Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden</title><title>JAMA neurology</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. OBJECTIVE: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. DESIGN, SETTING, AND PARTICIPANTS: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11–labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. MAIN OUTCOMES AND MEASURES: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. RESULTS: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 0.10; 95% CI, −0.08 to 0.28; P = .27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = −0.36; 95% CI, −0.34 to 0.09; P = .25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. CONCLUSIONS AND RELEVANCE: Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Carbolines</subject><subject>Cognitive Dysfunction - diagnostic imaging</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Cross-Sectional Studies</subject><subject>Diagnostic Self Evaluation</subject><subject>Entorhinal Cortex - diagnostic imaging</subject><subject>Entorhinal Cortex - metabolism</subject><subject>Female</subject><subject>Frontal Lobe - diagnostic imaging</subject><subject>Frontal Lobe - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neocortex - diagnostic imaging</subject><subject>Neocortex - metabolism</subject><subject>Parietal Lobe - diagnostic imaging</subject><subject>Parietal Lobe - metabolism</subject><subject>Phenanthrolines</subject><subject>Positron-Emission Tomography</subject><subject>Radiopharmaceuticals</subject><subject>Surveys and Questionnaires</subject><subject>tau Proteins - metabolism</subject><subject>Tauopathies - diagnostic imaging</subject><subject>Tauopathies - metabolism</subject><subject>Temporal Lobe - diagnostic imaging</subject><subject>Temporal Lobe - metabolism</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUd1qFDEUDqLYUvsCIjKX3sya_0xuhHWttVAo2IqXIckku1lmJmMyU9jX8kH6TGa7dau5ODnk-8lJPgDeIbhAEKKPW93rwc0pdgsMkVhgjPgLcFpqU3PExMtjT-UJOM95C8tqIKSEvgYnuJGCMIZOQfru1iEO9e3obPDBVsucow16KodV9NXtbLbOTuHeVau4HsJj98XZLgyu-hmmTXWn5zjqabOrrobWja6UYdpLL7todFc9_K6X_a6Loa0-z6mAb8Arr7vszp_2M_Dj68Xd6lt9fXN5tVpe15piMdUIM2qcJJ4awjRiWiJsGyiYb7jBnhkpiSGcN8Lw1rYSQmM997w8TQvsITkDnw6-42x619oyVtKdGlPoddqpqIP6HxnCRq3jvWJCUE5IMfjwZJDir9nlSfUhW9d15evjnBWSVEDJCW0KlR6oNsWck_PHaxBU-8TUc2Jqn5jaJ1Zk7_8d8Sj6m08hvD0QivoZ5YwTTMgfDDOf-g</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Buckley, Rachel F</creator><creator>Hanseeuw, Bernard</creator><creator>Schultz, Aaron P</creator><creator>Vannini, Patrizia</creator><creator>Aghjayan, Sarah L</creator><creator>Properzi, Michael J</creator><creator>Jackson, Jonathan D</creator><creator>Mormino, Elizabeth C</creator><creator>Rentz, Dorene M</creator><creator>Sperling, Reisa A</creator><creator>Johnson, Keith A</creator><creator>Amariglio, Rebecca E</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171201</creationdate><title>Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden</title><author>Buckley, Rachel F ; Hanseeuw, Bernard ; Schultz, Aaron P ; Vannini, Patrizia ; Aghjayan, Sarah L ; Properzi, Michael J ; Jackson, Jonathan D ; Mormino, Elizabeth C ; Rentz, Dorene M ; Sperling, Reisa A ; Johnson, Keith A ; Amariglio, Rebecca E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a427t-1254be93f4b35a15a912c8075f86b2f5b993b36687b6dcd900bcf6f6897a72f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Carbolines</topic><topic>Cognitive Dysfunction - diagnostic imaging</topic><topic>Cognitive Dysfunction - metabolism</topic><topic>Cross-Sectional Studies</topic><topic>Diagnostic Self Evaluation</topic><topic>Entorhinal Cortex - diagnostic imaging</topic><topic>Entorhinal Cortex - metabolism</topic><topic>Female</topic><topic>Frontal Lobe - diagnostic imaging</topic><topic>Frontal Lobe - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neocortex - diagnostic imaging</topic><topic>Neocortex - metabolism</topic><topic>Parietal Lobe - diagnostic imaging</topic><topic>Parietal Lobe - metabolism</topic><topic>Phenanthrolines</topic><topic>Positron-Emission Tomography</topic><topic>Radiopharmaceuticals</topic><topic>Surveys and Questionnaires</topic><topic>tau Proteins - metabolism</topic><topic>Tauopathies - diagnostic imaging</topic><topic>Tauopathies - metabolism</topic><topic>Temporal Lobe - diagnostic imaging</topic><topic>Temporal Lobe - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buckley, Rachel F</creatorcontrib><creatorcontrib>Hanseeuw, Bernard</creatorcontrib><creatorcontrib>Schultz, Aaron P</creatorcontrib><creatorcontrib>Vannini, Patrizia</creatorcontrib><creatorcontrib>Aghjayan, Sarah L</creatorcontrib><creatorcontrib>Properzi, Michael J</creatorcontrib><creatorcontrib>Jackson, Jonathan D</creatorcontrib><creatorcontrib>Mormino, Elizabeth C</creatorcontrib><creatorcontrib>Rentz, Dorene M</creatorcontrib><creatorcontrib>Sperling, Reisa A</creatorcontrib><creatorcontrib>Johnson, Keith A</creatorcontrib><creatorcontrib>Amariglio, Rebecca E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buckley, Rachel F</au><au>Hanseeuw, Bernard</au><au>Schultz, Aaron P</au><au>Vannini, Patrizia</au><au>Aghjayan, Sarah L</au><au>Properzi, Michael J</au><au>Jackson, Jonathan D</au><au>Mormino, Elizabeth C</au><au>Rentz, Dorene M</au><au>Sperling, Reisa A</au><au>Johnson, Keith A</au><au>Amariglio, Rebecca E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden</atitle><jtitle>JAMA neurology</jtitle><addtitle>JAMA Neurol</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>74</volume><issue>12</issue><spage>1455</spage><epage>1463</epage><pages>1455-1463</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. OBJECTIVE: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. DESIGN, SETTING, AND PARTICIPANTS: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11–labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. MAIN OUTCOMES AND MEASURES: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. RESULTS: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 0.10; 95% CI, −0.08 to 0.28; P = .27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = −0.36; 95% CI, −0.34 to 0.09; P = .25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. CONCLUSIONS AND RELEVANCE: Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>28973551</pmid><doi>10.1001/jamaneurol.2017.2216</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Amyloid beta-Peptides - metabolism Brain - diagnostic imaging Brain - metabolism Carbolines Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - metabolism Cross-Sectional Studies Diagnostic Self Evaluation Entorhinal Cortex - diagnostic imaging Entorhinal Cortex - metabolism Female Frontal Lobe - diagnostic imaging Frontal Lobe - metabolism Humans Male Middle Aged Neocortex - diagnostic imaging Neocortex - metabolism Parietal Lobe - diagnostic imaging Parietal Lobe - metabolism Phenanthrolines Positron-Emission Tomography Radiopharmaceuticals Surveys and Questionnaires tau Proteins - metabolism Tauopathies - diagnostic imaging Tauopathies - metabolism Temporal Lobe - diagnostic imaging Temporal Lobe - metabolism |
| title | Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden |
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