José A Luchsinger1,2, Priya Palta1,2, Brady Rippon1, Greysi Sherwood1, Luisa Soto1, Fernando Ceballos1, Krystal Laing3, Kay Igwe3, Hengda He3, Qolamreza Razlighi3,4,5,6, Jeanne Teresi7, Herman Moreno8, Adam M Brickman3,4,5. 1. Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center (CUIMC), New York, NY, USA. 2. Department of Epidemiology, Joseph P. Mailman School of Public Health, CUIMC, New York, NY, USA. 3. Department of Neurology, College of Physicians and Surgeons, CUIMC, New York, NY, USA. 4. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, CUIMC, New York, NY, USA. 5. Gertrude H. Sergievsky Center, CUIMC, New York, NY, USA. 6. Department of Biomedical Engineering, Columbia University, New York, NY, USA. 7. Research Division, Hebrew Home in Riverdale, Bronx, NY, USA. 8. Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Abstract
BACKGROUND: Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer's disease (AD), the most common cause of dementia, is unclear. OBJECTIVE: Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-β (Aβ), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. METHODS: We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain Aβ was ascertained as global Aβ standardized value uptake ratio using PET with 18F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). RESULTS: Mean age was 64.15±3.34 years, 72.00% were women, and 35.43% were APOEɛ4 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher Aβ compared with NGT. Type 2 diabetes treatment was related to lower Aβ. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. CONCLUSION: Pre-diabetes, but not type 2 diabetes, is associated with higher brain Aβ in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain Aβ. Whether type 2 diabetes treatment lowers brain Aβ requires further study.
BACKGROUND:Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer's disease (AD), the most common cause of dementia, is unclear. OBJECTIVE: Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-β (Aβ), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. METHODS: We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain Aβ was ascertained as global Aβ standardized value uptake ratio using PET with 18F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). RESULTS: Mean age was 64.15±3.34 years, 72.00% were women, and 35.43% were APOEɛ4 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher Aβ compared with NGT. Type 2 diabetes treatment was related to lower Aβ. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. CONCLUSION: Pre-diabetes, but not type 2 diabetes, is associated with higher brain Aβ in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain Aβ. Whether type 2 diabetes treatment lowers brain Aβ requires further study.
Entities:
Keywords:
Amyloid; Hispanic; middle age; type 2 diabetes
Authors: T Matsuzaki; K Sasaki; Y Tanizaki; J Hata; K Fujimi; Y Matsui; A Sekita; S O Suzuki; S Kanba; Y Kiyohara; T Iwaki Journal: Neurology Date: 2010-08-25 Impact factor: 9.910
Authors: Rik Ossenkoppele; Willemijn J Jansen; Gil D Rabinovici; Dirk L Knol; Wiesje M van der Flier; Bart N M van Berckel; Philip Scheltens; Pieter Jelle Visser; Sander C J Verfaillie; Marissa D Zwan; Sofie M Adriaanse; Adriaan A Lammertsma; Frederik Barkhof; William J Jagust; Bruce L Miller; Howard J Rosen; Susan M Landau; Victor L Villemagne; Christopher C Rowe; Dong Y Lee; Duk L Na; Sang W Seo; Marie Sarazin; Catherine M Roe; Osama Sabri; Henryk Barthel; Norman Koglin; John Hodges; Cristian E Leyton; Rik Vandenberghe; Koen van Laere; Alexander Drzezga; Stefan Forster; Timo Grimmer; Pascual Sánchez-Juan; Jose M Carril; Vincent Mok; Vincent Camus; William E Klunk; Ann D Cohen; Philipp T Meyer; Sabine Hellwig; Andrew Newberg; Kristian S Frederiksen; Adam S Fleisher; Mark A Mintun; David A Wolk; Agneta Nordberg; Juha O Rinne; Gaël Chételat; Alberto Lleo; Rafael Blesa; Juan Fortea; Karine Madsen; Karen M Rodrigue; David J Brooks Journal: JAMA Date: 2015-05-19 Impact factor: 56.272
Authors: Clifford R Jack; David S Knopman; William J Jagust; Leslie M Shaw; Paul S Aisen; Michael W Weiner; Ronald C Petersen; John Q Trojanowski Journal: Lancet Neurol Date: 2010-01 Impact factor: 44.182
Authors: Chris Moran; Richard Beare; Thanh G Phan; David G Bruce; Michele L Callisaya; Velandai Srikanth Journal: Neurology Date: 2015-09-02 Impact factor: 9.910
Authors: Clifford R Jack; David A Bennett; Kaj Blennow; Maria C Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P Rankin; Christopher C Rowe; Philip Scheltens; Eric Siemers; Heather M Snyder; Reisa Sperling Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Kelsey R Thomas; Alexandra J Weigand; Isabel H Cota; Emily C Edmonds; Christina E Wierenga; Mark W Bondi; Katherine J Bangen Journal: Brain Imaging Behav Date: 2021-08-20 Impact factor: 3.224
Authors: Olivia J Gannon; Lisa S Robison; Abigail E Salinero; Charly Abi-Ghanem; Febronia M Mansour; Richard D Kelly; Alvira Tyagi; Rebekah R Brawley; Jordan D Ogg; Kristen L Zuloaga Journal: J Neuroinflammation Date: 2022-05-14 Impact factor: 9.587
Authors: Priya Palta; Brady Rippon; Mouna Tahmi; Michelle Pardo; Aubrey Johnson; Zeljko Tomljanovic; Hengda He; Krystal K Laing; Qolamreza R Razlighi; Jeanne A Teresi; Herman Moreno; Adam M Brickman; William C Kreisl; José A Luchsinger Journal: Neurobiol Aging Date: 2021-03-23 Impact factor: 5.133
Authors: Shahram Oveisgharan; Ana W Capuano; Alifiya Kapasi; Aron S Buchman; Julie A Schneider; David A Bennett; Zoe Arvanitakis Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.160
Authors: Maria Jose Carranza-Naval; Maria Vargas-Soria; Carmen Hierro-Bujalance; Gloria Baena-Nieto; Monica Garcia-Alloza; Carmen Infante-Garcia; Angel Del Marco Journal: Biomolecules Date: 2021-02-10
Authors: Maria Jose Carranza-Naval; Angel Del Marco; Carmen Hierro-Bujalance; Pilar Alves-Martinez; Carmen Infante-Garcia; Maria Vargas-Soria; Marta Herrera; Belen Barba-Cordoba; Isabel Atienza-Navarro; Simon Lubian-Lopez; Monica Garcia-Alloza Journal: Front Aging Neurosci Date: 2021-12-16 Impact factor: 5.750