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Insulin Resistance in Cognitive Impairment
The InCHIANTI Study
Cristina Geroldi, MD, PhD;
Giovanni B. Frisoni, MD;
Giuseppe Paolisso, MD;
Stefania Bandinelli, MD;
Marco Lamponi, PT;
Angela Marie Abbatecola, MD;
Orazio Zanetti, MD;
Jack M. Guralnik, MD, PhD;
Luigi Ferrucci, MD, PhD
Arch Neurol. 2005;62:1067-1072.
Objective To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population.
Design Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI).
Participants A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score <25), 21 of whom had both cognitive impairment and subcortical features (CI/SF+ group). Control groups contained 23 individuals with a history of stroke and 381 individuals with no cognitive impairment (no CI group, MMSE score  25). Indicators of insulin resistance were the fasting plasma insulin level, insulin resistance index (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and insulin sensitivity index (Quantitative Insulin Sensitivity Check Index [QUICKI]).
Results The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF– group) was similar to that of individuals in the no CI group. Patients in the CI/SF– group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively).
Conclusions Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.
Author Affiliations: Laboratory of Epidemiology and Neuroimaging (Drs Geroldi and Frisoni) and Alzheimer’s Unit (Drs Geroldi and Zanetti), Istituto di Ricovero e Cura a Carattere Scientifico San Giovanni di Dio–Fatebenefratelli, Brescia, Italy; Associazione Fatebenefratelli per la Ricerca, Rome, Italy (Dr Frisoni); Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Naples, Italy (Drs Paolisso and Abbatecola); Laboratory of Clinical Epidemiology, Italian National Research Center on Aging Geriatric Department, Florence, Italy (Dr Bandinelli and Mr Lamponi); Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Md (Dr Guralnik); and Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Md (Dr Ferrucci).
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