title: Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele.
abstract: We conducted a preliminary case-control investigation of the association of pancreatic polypeptide (PP) with mild cognitive impairment (MCI) in 202 MCI cases (mean age, 81.6 years) and 202 age- and sex-matched cognitively normal controls in the Mayo Clinic Study of Aging. Plasma PP was measured and examined as the natural logarithm (continuous) and dichotomized at the median. The OR (95% CI) of MCI increased with increasing PP [1.46 (1.04-2.05)]. There was a negative interaction of PP with apolipoprotein E (APOE) ε4 allele; compared to the reference group (no APOE ε4 allele and low PP), the OR (95% CI) for combinations of ε4 and PP were: 2.64 (1.39-5.04) for APOE ε4 plus low PP; 2.09 (1.27-3.45) for no APOE ε4 plus high PP; and 1.91 (1.04-3.53) for no APOE ε4 plus high PP (P for interaction = 0.017). There was also a trend toward a negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to no diabetes and low PP, the OR (95% CI) was 3.02 (1.22-7.46) for low PP plus diabetes but 1.80 (1.01-3.22) for high PP plus diabetes. Participants with high PP had a greater mean (SD) weight loss (kilograms per decade) than persons with low PP [-2.27 (4.07) vs. -1.61 (5.24); P = 0.016]. MCI cases had a non-significantly greater weight loss per decade compared to controls. These findings suggest that high PP alone or jointly with APOE ε4 allele or type 2 diabetes is associated with MCI, and that high PP may mitigate some effects of APOE ε4 allele and type 2 diabetes on cognition. Potential mechanisms may involve PP-related weight loss and centrally mediated effects of PP on cognition. These findings remain to be validated in other studies.
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA ; Department of Neurology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA.
authors.forename: Jeremiah A
authors.initials: JA
authors.lastname: Aakre
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Cha
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kremers
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA ; Department of Neurology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Center for Clinical and Translational Science, Mayo Clinic , Rochester, MN , USA.
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Velgos
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic , Scottsdale, AZ , USA ; Department of Neurology, Mayo Clinic , Scottsdale, AZ , USA.
authors.forename: Yonas E
authors.initials: YE
authors.lastname: Geda
authors.affiliation: Department of Neurology, Mayo Clinic , Rochester, MN , USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA ; Department of Neurology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
keywords: apolipoprotein E; case–control study; cognition; mild cognitive impairment; neuropeptide; pancreatic polypeptide; type 2 diabetes