Blood pressure interacts with APOE ε4 to predict memory performance in a midlife sample.
OBJECTIVE
Elevated blood pressure and the Apolipoprotein ε4 allele (APOE ε4) are independent risk factors for Alzheimer's disease. We sought to determine whether the combined presence of the APOE ε4 allele and elevated blood pressure is associated with lower cognitive performance in cognitively healthy middle-aged adults.


METHODS
A total of 975 participants aged 30-54 (mean age = 44.47) were genotyped for APOE. Cardiometabolic risk factors including blood pressure, lipids, and glucose were assessed and cognitive function was measured using the Trail Making Test and the Visual Reproduction and Logical Memory subtests from the Wechsler Memory Scale.


RESULTS
Multivariable regression analysis showed that the association between APOE ε4 and episodic memory performance varied as a function of systolic blood pressure (SBP), such that elevated SBP was predictive of poorer episodic memory performance only in APOE ε4 carriers (β = -.092; t = -2.614; p = .009). Notably, this association was apparent at prehypertensive levels (≥130 mmHg), even after adjusting for physical activity, depression, smoking, and other cardiometabolic risk factors.


CONCLUSIONS
The joint presence of APOE ε4 and elevated SBP, even at prehypertensive levels, is associated with lower cognitive performance in healthy, middle-aged adults. Results of this study suggest that the combination of APOE ε4 and elevated SBP may synergistically compromise memory function well before the appearance of clinically significant impairments. Interventions targeting blood pressure control in APOE ε4 carriers during midlife should be studied as a possible means to reduce the risk of cognitive decline in genetically susceptible samples.
Department of Psychology, University of Pittsburgh.
Lauren E
LE
Oberlin
Department of Psychology, University of Pittsburgh.
Stephen B
SB
Manuck
Department of Psychology, University of Pittsburgh.
Peter J
PJ
Gianaros
Department of Human Genetics, University of Pittsburgh.
Robert E
RE
Ferrell
Heart and Vascular Institute, University of Pittsburgh School of Medicine.
Matthew F
MF
Muldoon
Department of Psychiatry, University of Pittsburgh.
J Richard
JR
Jennings
Department of Psychiatry, Mt. Sinai School of Medicine.
Janine D
JD
Flory
Department of Psychology, University of Pittsburgh.
Kirk I
KI
Erickson
D000328:Adult; D053327:Apolipoprotein E4 / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D058246:Prehypertension / Q000235:genetics / Q000523:psychology; D011597:Psychomotor Performance / Q000502:physiology*; D012907:Smoking / Q000523:psychology; D012959:Socioeconomic Factors; D014796:Visual Perception / Q000235:genetics / Q000502:physiology; D014888:Wechsler Scales
D053327:Apolipoprotein E4; D001786:Blood Glucose; D008055:Lipids