TY - JOUR
T1 - Is diabetes associated with increased pathological burden in Alzheimer's disease?
AU - Sadrolashrafi, Kaviyon
AU - Craft, Suzanne
AU - Decourt, Boris
AU - Adem, Abdu
AU - Wilson, Jeffrey R.
AU - Miller, Justin
AU - Sabbagh, Marwan N.
N1 - Funding Information:
Supported by NIH COBRE 5P20GM109025, R01AG059008, NIH P20 AG068054, and the Keep Memory Alive Foundation. The National Alzheimer's Coordinating Center (NACC) database is funded by NIA/National Institutes of Health Grant U01 AG016976. NACC data are contributed by the NIA‐funded Alzheimer Disease Centers: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
Funding Information:
Supported by NIH COBRE 5P20GM109025, R01AG059008, NIH P20 AG068054, and the Keep Memory Alive Foundation. The National Alzheimer's Coordinating Center (NACC) database is funded by NIA/National Institutes of Health Grant U01 AG016976. NACC data are contributed by the NIA-funded Alzheimer Disease Centers: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
Funding Information:
Kaviyon Sadrolashrafi has nothing to disclose. Dr. Craft discloses she is PI and director of the Wake Forest ADRC (P30 AG072947) and has grant support from U24 AG 057437, R01 Ag055122, R01 AG058969, R01 AG054523, R01 AG054069, RF1 AG058829, U19 AG063744, R03 AG 063299, R01 AG053798, R01 AG062624, R01 AG057725, R01 AG064014, R91 AG070883. She receives consulting fees from Roche, Biogen, Cortexyme, vTv Therapeutics, Renew Research, Cognito Therapeutics, T3D, and Philips Healthworks. She receives honoraria from PER, Knapp, and Medscape. She discloses one patent. Dr. DeCourt discloses grant support from NIH P20 AG 068053, R01AG59003, K01 AG047279. Dr. Adem has nothing to disclose. Dr. Wilson has nothing to disclose. Dr. Miller receives grant support from NIH P20 AG 068053 and P20 GM109025. Dr. Sabbagh discloses grant support from NIH P20 AG 068053, P20 AG109025, R01 059008; ownership interest (stock or stock options): Brain Health Inc, NeuroTau, Optimal Cognitive Health Company, uMethod Health, Versanum, Athira, Cognoptix; consulting: Alzheon, Biogen, Cortexyme, Roche‐Genentech, Stage 2 Innovations/Renew Research, Acadia, T3D, Eisai, KeifeRx; royalties: HarperCollins, Humanix.
Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association
PY - 2021
Y1 - 2021
N2 - Introduction: We examined the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) and hypothesized that diabetes is associated with an increased pathological burden in clinically and pathologically diagnosed AD. Methods: All data were obtained from the Uniform Data Set (UDS) v3, the Neuropathology Data Set, and the Researcher's Data Dictionary-Genetic Data from the National Alzheimer's Coordinating Center. The dataset (37 cases with diabetes and 1158 cases without) relies on autopsy-confirmed data in clinically diagnosed AD patients who were assessed for diabetes type in form A5 or D2 during at least one visit. Differences in scores were explored using a general linear model. Effect sizes were calculated using sample means and standard deviations (Cohen's d). Results: The presence of diabetes was associated with a lower Thal phase of amyloid plaques (A score; 4.6 ± 0.79 vs. 4.3 ± 0.85, P <.05) and lower Braak stage for neurofibrillary degeneration (B score; 5.58 ± 0.72 vs. 5.16 ± 0.96, P < 0.05) but not for density of neocortical neuritic plaques (CERAD score-C score). The National Institute on Aging–Alzheimer's Association Alzheimer's disease neuropathologic change (ABC score) was not different between AD+DM and AD-DM. Discussion: This pilot study found a significantly lower Thal phase of amyloid plaques and Braak stage for neurofibrillary degeneration in AD-confirmed individuals with diabetes compared to those without. Thus type 2 DM is not associated with increased AD pathology in clinically and pathologically confirmed cases of AD.
AB - Introduction: We examined the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) and hypothesized that diabetes is associated with an increased pathological burden in clinically and pathologically diagnosed AD. Methods: All data were obtained from the Uniform Data Set (UDS) v3, the Neuropathology Data Set, and the Researcher's Data Dictionary-Genetic Data from the National Alzheimer's Coordinating Center. The dataset (37 cases with diabetes and 1158 cases without) relies on autopsy-confirmed data in clinically diagnosed AD patients who were assessed for diabetes type in form A5 or D2 during at least one visit. Differences in scores were explored using a general linear model. Effect sizes were calculated using sample means and standard deviations (Cohen's d). Results: The presence of diabetes was associated with a lower Thal phase of amyloid plaques (A score; 4.6 ± 0.79 vs. 4.3 ± 0.85, P <.05) and lower Braak stage for neurofibrillary degeneration (B score; 5.58 ± 0.72 vs. 5.16 ± 0.96, P < 0.05) but not for density of neocortical neuritic plaques (CERAD score-C score). The National Institute on Aging–Alzheimer's Association Alzheimer's disease neuropathologic change (ABC score) was not different between AD+DM and AD-DM. Discussion: This pilot study found a significantly lower Thal phase of amyloid plaques and Braak stage for neurofibrillary degeneration in AD-confirmed individuals with diabetes compared to those without. Thus type 2 DM is not associated with increased AD pathology in clinically and pathologically confirmed cases of AD.
KW - Alzheimer's disease
KW - Alzheimer's disease neuropathologic change (ABC score)
KW - Braak neurofibrillary stage (B score)
KW - Thal phase (A score)
KW - neuritic plaque score (C score)
KW - type 2 diabetes mellitus
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U2 - 10.1002/dad2.12248
DO - 10.1002/dad2.12248
M3 - Article
AN - SCOPUS:85124388649
SN - 2352-8729
VL - 13
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
IS - 1
M1 - e12248
ER -