What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Cognitively unimpaired adults (n=87). Intervention: APOEε4 positive status vs. APOEε4 negative status. Primary outcome: Neurovascular coupling (percent change in middle cerebral artery blood velocity in response to the n-back test) (p=<0.05).

December 3, 2024Open Access

Lower neurovascular coupling response despite higher cerebral blood flow at rest in apolipoprotein ɛ4 positive adults

Q: What are the key findings of this study?

APOEε4 positive adults demonstrated lower neurovascular coupling responses compared to APOEε4 negative adults, despite having higher cerebral blood flow at rest.

Key Result

APOEε4 positive adults demonstrated lower neurovascular coupling responses compared to APOEε4 negative adults, despite having higher cerebral blood flow at rest.

Study Design

Type

Cross-Sectional (n=87)

Blinding

Single-blind

Multicenter

Structured PICO

Does APOEε4 positivity alter cerebral blood flow, cerebrovascular reactivity, and neurovascular coupling in cognitively unimpaired aging adults?

Population

87 cognitively unimpaired adults aged 55 to 69 years were evaluated to assess the impact of APOEε4 status on resting cerebral blood flow and cerebrovascular function.

Exposure

APOEε4 positive genotype (APOEε4+)

Comparator

APOEε4 negative genotype (APOEε4-)

Outcome

Neurovascular coupling (percent change in middle cerebral artery blood velocity in response to the n-back test), cerebrovascular reactivity to hypercapnia, and cerebral blood flow at restsurrogate

In cognitively unimpaired older adults, the APOEε4 allele is associated with impaired neurovascular coupling despite elevated resting cerebral blood flow, suggesting early cerebrovascular dysregulation precedes cognitive decline.

Main Result

p-value: p=<0.05

Limitations

The sample was primarily white, well-educated, and relatively healthy, which may limit generalizability to the broader population.
Measurement of middle cerebral artery velocity via transcranial Doppler ultrasound is an estimate of flow because it does not include vessel diameter.
The n-back cognitive test was not scored, preventing assessment of task performance or perceived difficulty.
All APOEε4+ carriers were grouped together, potentially masking differential impacts of specific genotypes (e.g., ε2/ε4 vs. ε3/ε4).
Potential confounding effects from chronic medication use (e.g., blood pressure medication, statins) among some participants.

Abstract

Cerebral blood flow at rest declines with age. However, age-related changes in functional measures of cerebrovascular health including cerebrovascular reactivity and neurovascular coupling are not well understood. Additionally, the effect of apolipoprotein E (APOE) ε4, a strong genetic risk factor for Alzheimer's disease, on cerebral blood flow and cerebrovascular function remains unclear. APOEε4 positive (APOEε4+; n = 37, age = 63±4y) and APOEε4 negative (APOEε4-; n = 50, age = 63±4y) cognitively unimpaired adults participated in this study. Macrovascular cerebral blood flow and microvascular cerebral perfusion were measured using 4D flow MRI and pseudo-continuous arterial spin labeling MRI, respectively. Cerebrovascular reactivity and neurovascular coupling were assessed by measuring middle cerebral artery blood velocity in response to hypercapnia and the n-back test, respectively. Neurovascular coupling was lower in APOEε4+ compared with APOEε4- adults (P<0.05), despite higher cerebral blood flow and cerebrovascular reactivity to hypercapnia. Alterations in neurovascular coupling may occur early, prior to changes in cognition, in aging APOEε4 carriers.

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