Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease

Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. OBJECTIVE To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-β (Aβ) levels in asymptomatic individuals with a parental history of AD dementia. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed Aβ1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and Aβ levels was then assessed using apolipoprotein E ϵ4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) Aβ biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. MAIN OUTCOMES AND MEASURES The association between proximity to parental symptom onset and Aβ burden in asymptomatic individuals with a parental history of sporadic AD. RESULTS The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF Aβ1-42 levels (range, 402-1597; B = -9.09, P = .04). This association was stronger in APOE4 carriers (B = -17.9, P = .03) and women (B = -19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. CONCLUSIONS AND RELEVANCE These results suggest that proximity to parental symptom onsetmay help estimate Aβ biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.

Original languageEnglish (US)
Pages (from-to)608-619
Number of pages12
JournalJAMA Neurology
Volume75
Issue number5
DOIs
StatePublished - May 1 2018

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Amyloid
Alzheimer Disease
Positron-Emission Tomography
Cerebrospinal Fluid
Carbon
Apolipoprotein E4
Adult Children
Registries
Age of Onset
Cohort Studies
Biomarkers
Parents
Spinal Puncture
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Therapeutics
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group (2018). Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease. JAMA Neurology, 75(5), 608-619. https://doi.org/10.1001/jamaneurol.2017.5135

Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease. / Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group.

In: JAMA Neurology, Vol. 75, No. 5, 01.05.2018, p. 608-619.

Research output: Contribution to journalArticle

Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group 2018, 'Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease', JAMA Neurology, vol. 75, no. 5, pp. 608-619. https://doi.org/10.1001/jamaneurol.2017.5135
Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group. Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease. JAMA Neurology. 2018 May 1;75(5):608-619. https://doi.org/10.1001/jamaneurol.2017.5135
Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group. / Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease. In: JAMA Neurology. 2018 ; Vol. 75, No. 5. pp. 608-619.
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abstract = "IMPORTANCE Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. OBJECTIVE To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-β (Aβ) levels in asymptomatic individuals with a parental history of AD dementia. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed Aβ1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and Aβ levels was then assessed using apolipoprotein E ϵ4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) Aβ biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. MAIN OUTCOMES AND MEASURES The association between proximity to parental symptom onset and Aβ burden in asymptomatic individuals with a parental history of sporadic AD. RESULTS The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7{\%}] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7{\%}] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2{\%}] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8{\%}] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9{\%}] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF Aβ1-42 levels (range, 402-1597; B = -9.09, P = .04). This association was stronger in APOE4 carriers (B = -17.9, P = .03) and women (B = -19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. CONCLUSIONS AND RELEVANCE These results suggest that proximity to parental symptom onsetmay help estimate Aβ biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.",
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T1 - Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease

AU - Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group

AU - Villeneuve, Sylvia

AU - Vogel, Jacob W.

AU - Gonneaud, Julie

AU - Pichet Binette, Alexa

AU - Rosa-Neto, Pedro

AU - Gauthier, Serge

AU - Bateman, Randall J.

AU - Fagan, Anne M.

AU - Morris, John C.

AU - Benzinger, Tammie L.S.

AU - Johnson, Sterling C.

AU - Breitner, John C.S.

AU - Poirier, Judes

AU - Barkun, Alan

AU - Evans, Alan

AU - Salaciak, Alyssa

AU - Tam, Angela

AU - Labonté, Anne

AU - Faubert, Anne Marie

AU - Mathieu, Axel

AU - Courcot, Blandine

AU - Hyman, Bradley T.

AU - Madjar, Cécile

AU - Carrier, Charles Edouard

AU - Dansereau, Christian

AU - Kazazian, Christina

AU - Tardif, Christine

AU - Lepage, Claude

AU - Cuello, Claudio

AU - Debacker, Clément

AU - Jack, Clifford R Jr.

AU - Picard, Cynthia

AU - Maillet, David

AU - Fontaine, David

AU - Knopman, David S

AU - Michaud, Diane

AU - Couture, Doris

AU - Dea, Doris

AU - Teigner, Eduard

AU - Anthal, Elena

AU - Yu, Elsa

AU - Vachon-Presseau, Etienne

AU - Saint-Fort, Eunice Farah

AU - Ferdinand, Fabiola

AU - Benbouhoud, Fatiha

AU - Pogossova, Galina

AU - Maultaup, Gerhard

AU - Mayrand, Ginette

AU - Duclair, Guerda

AU - Ayranci, Gülebru

PY - 2018/5/1

Y1 - 2018/5/1

N2 - IMPORTANCE Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. OBJECTIVE To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-β (Aβ) levels in asymptomatic individuals with a parental history of AD dementia. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed Aβ1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and Aβ levels was then assessed using apolipoprotein E ϵ4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) Aβ biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. MAIN OUTCOMES AND MEASURES The association between proximity to parental symptom onset and Aβ burden in asymptomatic individuals with a parental history of sporadic AD. RESULTS The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF Aβ1-42 levels (range, 402-1597; B = -9.09, P = .04). This association was stronger in APOE4 carriers (B = -17.9, P = .03) and women (B = -19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. CONCLUSIONS AND RELEVANCE These results suggest that proximity to parental symptom onsetmay help estimate Aβ biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.

AB - IMPORTANCE Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. OBJECTIVE To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-β (Aβ) levels in asymptomatic individuals with a parental history of AD dementia. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed Aβ1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and Aβ levels was then assessed using apolipoprotein E ϵ4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) Aβ biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. MAIN OUTCOMES AND MEASURES The association between proximity to parental symptom onset and Aβ burden in asymptomatic individuals with a parental history of sporadic AD. RESULTS The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF Aβ1-42 levels (range, 402-1597; B = -9.09, P = .04). This association was stronger in APOE4 carriers (B = -17.9, P = .03) and women (B = -19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. CONCLUSIONS AND RELEVANCE These results suggest that proximity to parental symptom onsetmay help estimate Aβ biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.

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