Peripheral insulin and brain structure in early Alzheimer disease.
OBJECTIVE
Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD.


METHODS
Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity.


RESULTS
In early AD, insulin and glucose AUCs were related to whole brain (insulin beta = 0.66, p < 0.001; glucose beta = 0.45, p < 0.01) and hippocampal volume (insulin beta = 0.42, p < 0.05; glucose beta = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (beta = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = -0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals.


CONCLUSIONS
Increased peripheral insulin is associated with reduced Alzheimer disease (AD)-related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD.
Burns
J M
JM
University of Kansas School of Medicine, Kansas City, KS 66160, USA. jburns2@kumc.edu
Donnelly
J E
JE
Anderson
H S
HS
Mayo
M S
MS
Spencer-Gardner
L
L
Thomas
G
G
Cronk
B B
BB
Haddad
Z
Z
Klima
D
D
Hansen
D
D
Brooks
W M
WM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019540:Area Under Curve; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005951:Glucose Tolerance Test; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
D001786:Blood Glucose; D007328:Insulin