Insulin resistance is associated with poorer verbal fluency performance in women.
OBJECTIVE
Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association.


METHODS
The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests.


RESULTS
Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02).


CONCLUSIONS
To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.
Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland. llekbl@utu.fi.|Turku Health Care Centre, Turku, Finland. llekbl@utu.fi.
Laura L
http://orcid.org/0000-0002-5863-8088
LL
Ekblad
Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland.|Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
Juha O
JO
Rinne
National Institute for Health and Welfare (THL), Turku, Finland.
Pauli J
PJ
Puukka
Turku City Hospital, University of Turku, Turku, Finland.|Department of Medicine, University of Turku, Turku, Finland.
Hanna K
HK
Laine
University of Eastern Finland, Kuopio, Finland.
Satu E
SE
Ahtiluoto
University of Eastern Finland, Kuopio, Finland.
Raimo O
RO
Sulkava
Turku City Hospital, University of Turku, Turku, Finland.|Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
Matti H
MH
Viitanen
National Institute for Health and Welfare (THL), Turku, Finland.
Antti M
AM
Jula
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012307:Risk Factors; D012737:Sex Factors; D014705:Verbal Behavior / Q000502:physiology*
D001057:Apolipoproteins E; D001786:Blood Glucose
APOE*E4 genotype; Alzheimer’s disease; Categorical verbal fluency; Cognition; HOMA-IR; Insulin resistance; Sex difference