The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND
Background The effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study. Method Participants ag...
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| Veröffentlicht in: | Alzheimer's & dementia 2023-06, Vol.19 (S2), p.n/a |
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| creator | Hayden, Kathleen M. Evans, Joni K Culkin, Margaret C. Molina‐Henry, Doris P Marcovina, Santica Shappell, Heather M Rapp, Stephen R. Sachs, Bonnie C. Ding, Jingzhong Mielke, Michelle M. Luchsinger, Jose A Espeland, Mark A. |
| description | Background
The effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.
Method
Participants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.
Result
The mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p |
| doi_str_mv | 10.1002/alz.063408 |
| format | Article |
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The effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.
Method
Participants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.
Result
The mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p<0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).
Conclusion
There was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.</description><identifier>ISSN: 1552-5260</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.063408</identifier><language>eng</language><ispartof>Alzheimer's & dementia, 2023-06, Vol.19 (S2), p.n/a</ispartof><rights>2023 the Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falz.063408$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falz.063408$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Hayden, Kathleen M.</creatorcontrib><creatorcontrib>Evans, Joni K</creatorcontrib><creatorcontrib>Culkin, Margaret C.</creatorcontrib><creatorcontrib>Molina‐Henry, Doris P</creatorcontrib><creatorcontrib>Marcovina, Santica</creatorcontrib><creatorcontrib>Shappell, Heather M</creatorcontrib><creatorcontrib>Rapp, Stephen R.</creatorcontrib><creatorcontrib>Sachs, Bonnie C.</creatorcontrib><creatorcontrib>Ding, Jingzhong</creatorcontrib><creatorcontrib>Mielke, Michelle M.</creatorcontrib><creatorcontrib>Luchsinger, Jose A</creatorcontrib><creatorcontrib>Espeland, Mark A.</creatorcontrib><title>The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND</title><title>Alzheimer's & dementia</title><description>Background
The effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.
Method
Participants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.
Result
The mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p<0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).
Conclusion
There was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.</description><issn>1552-5260</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kL1OwzAUhS0EEqWw8ASekVJsp26SMWpLWynAUhaWyD831DSJKzuiaqeOjKy8Xp-ElFaMTPfvu0c6B6FbSnqUEHYvym2PDMI-ic9Qh3LOAs6i5PyvH5BLdOX9OyEtQnkHfc4XgIX3VhnRGFtjCc0aoMZpuV2AqcDtd98ea-NBeMCytFbvd1-yHTSWxlbCLcF5LGqNlX2rTWM-AJtqJYyroG5-DytnpZAlYA2HnRHY1DizdonT6Tgd4cfZ0-gaXRSi9HBzql308jCeD6dB9jyZDdMsUJSGcSAZkzpWMTDO40RGiYK-TCiPiFZK6AiEUKQYtKa5VFz2CxWKooh0JJiGkMmwi-6OuspZ7x0U-cqZ1sUmpyQ_ZJi3GebHDFuYHuG1KWHzD5mn2evp5wdomXjg</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Hayden, Kathleen M.</creator><creator>Evans, Joni K</creator><creator>Culkin, Margaret C.</creator><creator>Molina‐Henry, Doris P</creator><creator>Marcovina, Santica</creator><creator>Shappell, Heather M</creator><creator>Rapp, Stephen R.</creator><creator>Sachs, Bonnie C.</creator><creator>Ding, Jingzhong</creator><creator>Mielke, Michelle M.</creator><creator>Luchsinger, Jose A</creator><creator>Espeland, Mark A.</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>202306</creationdate><title>The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND</title><author>Hayden, Kathleen M. ; Evans, Joni K ; Culkin, Margaret C. ; Molina‐Henry, Doris P ; Marcovina, Santica ; Shappell, Heather M ; Rapp, Stephen R. ; Sachs, Bonnie C. ; Ding, Jingzhong ; Mielke, Michelle M. ; Luchsinger, Jose A ; Espeland, Mark A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1138-b22bd8c8e25589b79ce4b91570dccad7eaac0f62795bc5b4fc3aff7d7a2de32b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayden, Kathleen M.</creatorcontrib><creatorcontrib>Evans, Joni K</creatorcontrib><creatorcontrib>Culkin, Margaret C.</creatorcontrib><creatorcontrib>Molina‐Henry, Doris P</creatorcontrib><creatorcontrib>Marcovina, Santica</creatorcontrib><creatorcontrib>Shappell, Heather M</creatorcontrib><creatorcontrib>Rapp, Stephen R.</creatorcontrib><creatorcontrib>Sachs, Bonnie C.</creatorcontrib><creatorcontrib>Ding, Jingzhong</creatorcontrib><creatorcontrib>Mielke, Michelle M.</creatorcontrib><creatorcontrib>Luchsinger, Jose A</creatorcontrib><creatorcontrib>Espeland, Mark A.</creatorcontrib><collection>CrossRef</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayden, Kathleen M.</au><au>Evans, Joni K</au><au>Culkin, Margaret C.</au><au>Molina‐Henry, Doris P</au><au>Marcovina, Santica</au><au>Shappell, Heather M</au><au>Rapp, Stephen R.</au><au>Sachs, Bonnie C.</au><au>Ding, Jingzhong</au><au>Mielke, Michelle M.</au><au>Luchsinger, Jose A</au><au>Espeland, Mark A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND</atitle><jtitle>Alzheimer's & dementia</jtitle><date>2023-06</date><risdate>2023</risdate><volume>19</volume><issue>S2</issue><epage>n/a</epage><issn>1552-5260</issn><eissn>1552-5279</eissn><abstract>Background
The effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.
Method
Participants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.
Result
The mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p<0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).
Conclusion
There was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.</abstract><doi>10.1002/alz.063408</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| title | The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND |
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