TY - JOUR
T1 - DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease
AU - Sala-Vila, Aleix
AU - Arenaza-Urquijo, Eider M.
AU - Sánchez-Benavides, Gonzalo
AU - Suárez-Calvet, Marc
AU - Milà-Alomà, Marta
AU - Grau-Rivera, Oriol
AU - González-de-Echávarri, José M.
AU - Crous-Bou, Marta
AU - Minguillón, Carolina
AU - Fauria, Karine
AU - Operto, Grégory
AU - Falcón, Carles
AU - Salvadó, Gemma
AU - Cacciaglia, Raffaele
AU - Ingala, Silvia
AU - Barkhof, Frederik
AU - Schröder, Helmut
AU - ALFA Study
AU - Scarmeas, Nikolaos
AU - Gispert, Juan-Domingo
AU - Molinuevo, José L.
N1 - Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - BACKGROUND: The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n-3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI. OBJECTIVES: We aimed, in middle-aged cognitively unimpaired individuals at increased risk of AD, to cross-sectionally investigate whether dietary DHA intake relates to cognitive performance and to MRI-based markers of cerebral small vessel disease and AD-related neurodegeneration, exploring the effect modification by APOE-ε4 status. METHODS: In 340 participants of the ALFA (ALzheimer and FAmilies) study, which is enriched for APOE-ε4 carriership (n = 122, noncarriers; n = 157, 1 allele; n = 61, 2 alleles), we assessed self-reported DHA intake through an FFQ. We measured cognitive performance by administering episodic memory and executive function tests. We performed high-resolution structural MRI to assess cerebral small vessel disease [white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs)] and AD-related brain atrophy (cortical thickness in an AD signature). We constructed regression models adjusted for potential confounders, exploring the interaction DHA × APOE-ε4. RESULTS: We observed no significant associations between DHA and cognitive performance or WMH burden. We observed a nonsignificant inverse association between DHA and prevalence of lobar CMBs (OR: 0.446; 95% CI: 0.195, 1.018; P = 0.055). DHA was found to be significantly related to greater cortical thickness in the AD signature in homozygotes but not in nonhomozygotes (P-interaction = 0.045). The association strengthened when analyzing homozygotes and nonhomozygotes matched for risk factors. CONCLUSIONS: In cognitively unimpaired APOE-ε4 homozygotes, dietary DHA intake related to structural patterns that may result in greater resilience to AD pathology. This is consistent with the current hypothesis that those subjects at highest risk would obtain the largest benefits from DHA supplementation in the preclinical stage.This trial was registered at clinicaltrials.gov as NCT01835717.
AB - BACKGROUND: The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n-3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI. OBJECTIVES: We aimed, in middle-aged cognitively unimpaired individuals at increased risk of AD, to cross-sectionally investigate whether dietary DHA intake relates to cognitive performance and to MRI-based markers of cerebral small vessel disease and AD-related neurodegeneration, exploring the effect modification by APOE-ε4 status. METHODS: In 340 participants of the ALFA (ALzheimer and FAmilies) study, which is enriched for APOE-ε4 carriership (n = 122, noncarriers; n = 157, 1 allele; n = 61, 2 alleles), we assessed self-reported DHA intake through an FFQ. We measured cognitive performance by administering episodic memory and executive function tests. We performed high-resolution structural MRI to assess cerebral small vessel disease [white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs)] and AD-related brain atrophy (cortical thickness in an AD signature). We constructed regression models adjusted for potential confounders, exploring the interaction DHA × APOE-ε4. RESULTS: We observed no significant associations between DHA and cognitive performance or WMH burden. We observed a nonsignificant inverse association between DHA and prevalence of lobar CMBs (OR: 0.446; 95% CI: 0.195, 1.018; P = 0.055). DHA was found to be significantly related to greater cortical thickness in the AD signature in homozygotes but not in nonhomozygotes (P-interaction = 0.045). The association strengthened when analyzing homozygotes and nonhomozygotes matched for risk factors. CONCLUSIONS: In cognitively unimpaired APOE-ε4 homozygotes, dietary DHA intake related to structural patterns that may result in greater resilience to AD pathology. This is consistent with the current hypothesis that those subjects at highest risk would obtain the largest benefits from DHA supplementation in the preclinical stage.This trial was registered at clinicaltrials.gov as NCT01835717.
KW - brain atrophy
KW - cerebral small vessel disease
KW - cognition
KW - markers
KW - omega-3 fatty acids
KW - white matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85107390385&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/ajcn/nqab016
DO - https://doi.org/10.1093/ajcn/nqab016
M3 - Article
C2 - 33733657
SN - 0002-9165
VL - 113
SP - 1627
EP - 1635
JO - The American journal of clinical nutrition
JF - The American journal of clinical nutrition
IS - 6
ER -