APOE gene-dependent BOLD responses to a breath-hold across the adult lifespan

Autor: Michael Christiansen, Peter Mondrup Rasmussen, Torben Ellegaard Lund, Leif Østergaard, Eddie Weitzberg, Rasmus Aamand
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Apolipoprotein E
Aging
Haemodynamic response
Apolipoprotein E4
Apolipoprotein E3
Hemodynamics
Stimulation
lcsh:RC346-429
Breath Holding
0302 clinical medicine
Cerebrovascular reactivity
Cross-Over Studies
medicine.diagnostic_test
05 social sciences
Regular Article
Middle Aged
Alzheimer's disease
Breath-hold
Magnetic Resonance Imaging
Neurology
Cerebrovascular Circulation
lcsh:R858-859.7
Female
Adult
medicine.medical_specialty
Genotype
Cognitive Neuroscience
Longevity
lcsh:Computer applications to medicine. Medical informatics
050105 experimental psychology
03 medical and health sciences
Apolipoproteins E
Double-Blind Method
Internal medicine
medicine
Humans
0501 psychology and cognitive sciences
Radiology
Nuclear Medicine and imaging
BOLD fMRI
lcsh:Neurology. Diseases of the nervous system
Aged
Nitrates
business.industry
Crossover study
Ageing
Endocrinology
Neurology (clinical)
Functional magnetic resonance imaging
business
Asymptomatic carrier
030217 neurology & neurosurgery
Zdroj: NeuroImage: Clinical, Vol 24, Iss, Pp-(2019)
Rasmussen, P M, Aamand, R, Weitzberg, E, Christiansen, M, Østergaard, L & Lund, T E 2019, ' APOE gene-dependent BOLD responses to a breath-hold across the adult lifespan ', NeuroImage: Clinical, vol. 24, 101955 . https://doi.org/10.1016/j.nicl.2019.101955
NeuroImage : Clinical
ISSN: 2213-1582
DOI: 10.1016/j.nicl.2019.101955
Popis: Age and apolipoprotein E (APOE) e4 genotype are two of the strongest known risk factors for sporadic Alzheimer's disease (AD). Neuroimaging has shown hemodynamic response changes with age, in asymptomatic carriers of the APOE e4 allele, and in AD. In this study, we aimed to characterize and differentiate age- and APOE gene-specific hemodynamic changes to breath-hold and visual stimulation. A further aim was to study whether these responses were modulated by 3-day intake of nitrate, a nitric oxide (NO) source. The study was designed as a randomized, double-blinded, placebo-controlled crossover study, and the study cohort comprised 41 APOE e4 carriers (e3/e4 or e4/e4 genotype) and 40 non-carriers (e3/e3 genotype) aged 30–70 years at enrollment. The participants underwent two scanning sessions, each preceded by ingestion of sodium nitrate or sodium chloride (control). During functional magnetic resonance imaging (fMRI) sessions, participants performed two concurrent tasks; a breath-hold task to probe cerebrovascular reactivity and a visual stimulation task to evoke functional hyperemia, respectively. We found that the blood oxygenation level dependent (BOLD) hemodynamic response to breath-hold was altered in APOE e4 carriers relative to non-carriers. Mid-aged (50–60 years of age) e4 carriers exhibited a significantly increased peak time relative to mid-aged e3 carriers, and peak time for younger (30–40 years of age) e4 carriers was significantly shorter than that of mid-aged e4 carriers. The response width was significantly increased for e4 carriers. The response peak magnitude significantly decreased with age. For the visual stimulation task, we found age-related changes, with reduced response magnitude with age but no significant effect of APOE allele type. We found no effect of nitrate ingestion on BOLD responses evoked by the breath-hold and visual stimulation tasks. The APOE gene-dependent response to breath-hold may reflect NO-independent differences in vascular function.
Highlights • Age and APOE e4 genotype are two of the strongest known risk factors for sporadic Alzheimer’s disease. • We characterized and differentiated age- and APOE gene-specific hemodynamic changes to breath-hold and visual stimulation. • We found altered temporal dynamics of BOLD responses to breath-hold in APOE e4 carriers relative to non-carriers. • We found differential age-related changes in BOLD responses to breath-hold across APOE types. • We found age-related changes in BOLD responses to visual stimulation.
Databáze: OpenAIRE
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