Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly.
OBJECTIVE
Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.


METHODS
Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).


RESULTS
The HOMA-IR was negatively correlated with verbal fluency performance, brain size, and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.


CONCLUSIONS
These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
Department of Neuroscience, Uppsala University, Uppsala, Sweden. christian.benedict@neuro.uu.se
Christian
C
Benedict
Samantha J
SJ
Brooks
Joel
J
Kullberg
Jonathan
J
Burgos
Matthew J
MJ
Kempton
Richard
R
Nordenskjöld
Ruta
R
Nylander
Lena
L
Kilander
Suzanne
S
Craft
Elna-Marie
EM
Larsson
Lars
L
Johansson
Håkan
H
Ahlström
Lars
L
Lind
Helgi B
HB
Schiöth
D000368:Aged; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D013702:Temporal Lobe / Q000033:anatomy & histology*; D014705:Verbal Behavior / Q000502:physiology*