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Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele.

Roberts RO, Aakre JA, Cha RH, Kremers WK, Mielke MM, Velgos SN, Geda YE, Knopman DS, Petersen RC - Front Aging Neurosci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA ; Department of Neurology, Mayo Clinic , Rochester, MN , USA.

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.

No MeSH data available.


Related in: MedlinePlus

Interaction of pancreatic polypeptide (PP) with APOE ε4 Allele. Compared to persons without an APOE ε4 allele and low PP level (reference), the ORs (95% CIs) were as follows: 2.64 (1.39–5.04), P = 0.003 for low PP plus APOE ε4 allele; 2.09 (1.27–3.45), P = 0.004 for high PP without APOE ε4 allele; and 1.91 (1.04–3.53), P = 0.038 for high PP plus APOE ε4 allele. PP was dichotomized at the median as low PP (≤196 pg/mL) and high PP (>196 pg/mL).
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Figure 1: Interaction of pancreatic polypeptide (PP) with APOE ε4 Allele. Compared to persons without an APOE ε4 allele and low PP level (reference), the ORs (95% CIs) were as follows: 2.64 (1.39–5.04), P = 0.003 for low PP plus APOE ε4 allele; 2.09 (1.27–3.45), P = 0.004 for high PP without APOE ε4 allele; and 1.91 (1.04–3.53), P = 0.038 for high PP plus APOE ε4 allele. PP was dichotomized at the median as low PP (≤196 pg/mL) and high PP (>196 pg/mL).

Mentions: We observed a significant interaction of PP with APOE ε4 allele (P for interaction = 0.017). The joint effects of high PP and APOE ε4 allele were indicative of a negative (antagonistic) interaction. Compared to the reference group (no APOE ε4 allele and low PP), the ORs (95% CIs) for combinations of APOE and PP were as follows: 2.64 (1.39–5.04), P = 0.003 for APOE ε4 plus low PP; 2.09 (1.27–3.45), P = 0.004 for no APOE ε4 plus high PP; and 1.91 (1.04–3.53), P = 0.038 for APOE ε4 plus high PP (Figure 1). There was also a marginal negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to the reference group (no type 2 diabetes and low PP), the ORs (95% CIs) of MCI were: 3.02 (1.22–7.46), P = 0.017 for diabetes plus low PP; 1.69 (1.07–2.68), P = 0.026 for no diabetes plus high PP; and 1.80 (1.01–3.22), P = 0.046 for diabetes plus high PP (Figure 2).


Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele.

Roberts RO, Aakre JA, Cha RH, Kremers WK, Mielke MM, Velgos SN, Geda YE, Knopman DS, Petersen RC - Front Aging Neurosci (2015)

Interaction of pancreatic polypeptide (PP) with APOE ε4 Allele. Compared to persons without an APOE ε4 allele and low PP level (reference), the ORs (95% CIs) were as follows: 2.64 (1.39–5.04), P = 0.003 for low PP plus APOE ε4 allele; 2.09 (1.27–3.45), P = 0.004 for high PP without APOE ε4 allele; and 1.91 (1.04–3.53), P = 0.038 for high PP plus APOE ε4 allele. PP was dichotomized at the median as low PP (≤196 pg/mL) and high PP (>196 pg/mL).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561818&req=5

Figure 1: Interaction of pancreatic polypeptide (PP) with APOE ε4 Allele. Compared to persons without an APOE ε4 allele and low PP level (reference), the ORs (95% CIs) were as follows: 2.64 (1.39–5.04), P = 0.003 for low PP plus APOE ε4 allele; 2.09 (1.27–3.45), P = 0.004 for high PP without APOE ε4 allele; and 1.91 (1.04–3.53), P = 0.038 for high PP plus APOE ε4 allele. PP was dichotomized at the median as low PP (≤196 pg/mL) and high PP (>196 pg/mL).
Mentions: We observed a significant interaction of PP with APOE ε4 allele (P for interaction = 0.017). The joint effects of high PP and APOE ε4 allele were indicative of a negative (antagonistic) interaction. Compared to the reference group (no APOE ε4 allele and low PP), the ORs (95% CIs) for combinations of APOE and PP were as follows: 2.64 (1.39–5.04), P = 0.003 for APOE ε4 plus low PP; 2.09 (1.27–3.45), P = 0.004 for no APOE ε4 plus high PP; and 1.91 (1.04–3.53), P = 0.038 for APOE ε4 plus high PP (Figure 1). There was also a marginal negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to the reference group (no type 2 diabetes and low PP), the ORs (95% CIs) of MCI were: 3.02 (1.22–7.46), P = 0.017 for diabetes plus low PP; 1.69 (1.07–2.68), P = 0.026 for no diabetes plus high PP; and 1.80 (1.01–3.22), P = 0.046 for diabetes plus high PP (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic , Rochester, MN , USA ; Department of Neurology, Mayo Clinic , Rochester, MN , USA.

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.

No MeSH data available.


Related in: MedlinePlus