Type 2 Diabetes Mellitus is Associated with Brain Atrophy and Hypometabolism in the ADNI Cohort

Overview

Journal Neurology

Specialty Neurology

Date 2016 Jul 8

PMID 27385744

Citations 48

Authors

Wei Li

Shannon L Risacher

Edgar Huang

Andrew J Saykin

Affiliations

Soon will be listed here.

Abstract

Objective: We investigated type 2 diabetes mellitus (T2DM) as a risk factor for brain atrophy and glucose hypometabolism in older adults with or at risk of cognitive impairment.

Methods: Participants with the T2DM were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1/GO/2 cohorts). Analysis of covariance models were used to compare participants with and without T2DM, controlling for potential confounding factors.

Results: Whole brain volume and whole brain [(18)F]-fluorodeoxyglucose (FDG) uptake were significantly different as a function of T2DM status, independent of baseline clinical diagnosis. On post hoc analysis, a lower whole brain volume was seen in participants with both mild cognitive impairment (MCI) and T2DM (n = 76) compared with participants who had MCI but not T2DM (n = 747; p = 0.009). Similarly, mean FDG uptake in gray matter and white matter was lower in participants with both MCI and T2DM (n = 72) than in participants with MCI without T2DM (n = 719; p = 0.04). Subsequent regional analysis revealed that the decreased FDG uptake in participants with both MCI and T2DM was mainly manifested in 3 brain regions: frontal lobe, sensory motor cortex, and striatum.

Conclusions: T2DM may accelerate cognition deterioration in patients with MCI by affecting glucose metabolism and brain volume.

Citing Articles

Relationships Between Brain Glucose Metabolism Patterns and Impaired Glycemic Status: A Systematic Review of FDG-PET Studies With a Focus on Alzheimer's Disease.

Soltani S, Dolatshahi M, Soltani S, Khazaei K, Rahmani M, Raji C Hum Brain Mapp. 2025; 46(4):e70180.

PMID: 40033766 PMC: 11876560. DOI: 10.1002/hbm.70180.

APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI.

Lathika Rajendrakumar A, Arbeev K, Bagley O, Duan M, Yashin A, Ukraintseva S PLoS One. 2025; 20(1):e0316808.

PMID: 39774485 PMC: 11706463. DOI: 10.1371/journal.pone.0316808.

Metformin effectively alleviates the symptoms of Alzheimer in rats by lowering amyloid β deposition and enhancing the insulin signal.

Abosharaf H, Elsonbaty Y, Tousson E, Mohamed T Metab Brain Dis. 2024; 40(1):41.

PMID: 39585487 PMC: 11588952. DOI: 10.1007/s11011-024-01422-8.

and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer's Pathology: New Findings from the ADNI.

Lathika Rajendrakumar A, Arbeev K, Bagley O, Duan M, Yashin A, Ukraintseva S medRxiv. 2024; .

PMID: 39314962 PMC: 11419198. DOI: 10.1101/2024.09.13.24313582.

Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer's disease.

Liang N, Nho K, Newman J, Arnold M, Huynh K, Meikle P Sci Rep. 2024; 14(1):17423.

PMID: 39075118 PMC: 11286782. DOI: 10.1038/s41598-024-67177-5.

References

Trojanowski J, Vandeerstichele H, Korecka M, Clark C, Aisen P, Petersen R . Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects. Alzheimers Dement. 2010; 6(3):230-8. PMC: 2867838. DOI: 10.1016/j.jalz.2010.03.008. View

Luchsinger J, Reitz C, Patel B, Tang M, Manly J, Mayeux R . Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007; 64(4):570-5. DOI: 10.1001/archneur.64.4.570. View

Lee Y, Kang H, Kim N, Yang J, Noh J, Ko K . Factors associated for mild cognitive impairment in older korean adults with type 2 diabetes mellitus. Diabetes Metab J. 2014; 38(2):150-7. PMC: 4021302. DOI: 10.4093/dmj.2014.38.2.150. View

Biessels G, Reijmer Y . Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI?. Diabetes. 2014; 63(7):2244-52. DOI: 10.2337/db14-0348. View

Moran C, Phan T, Chen J, Blizzard L, Beare R, Venn A . Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care. 2013; 36(12):4036-42. PMC: 3836136. DOI: 10.2337/dc13-0143. View

Petersen R, Aisen P, Beckett L, Donohue M, Gamst A, Harvey D . Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010; 74(3):201-9. PMC: 2809036. DOI: 10.1212/WNL.0b013e3181cb3e25. View

Heitner J, Dickson D . Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology. 1997; 49(5):1306-11. DOI: 10.1212/wnl.49.5.1306. View

Weiner M, Aisen P, Jack Jr C, Jagust W, Trojanowski J, Shaw L . The Alzheimer's disease neuroimaging initiative: progress report and future plans. Alzheimers Dement. 2010; 6(3):202-11.e7. PMC: 2927112. DOI: 10.1016/j.jalz.2010.03.007. View

Gorska-Ciebiada M, Saryusz-Wolska M, Ciebiada M, Loba J . Mild cognitive impairment and depressive symptoms in elderly patients with diabetes: prevalence, risk factors, and comorbidity. J Diabetes Res. 2014; 2014:179648. PMC: 4241577. DOI: 10.1155/2014/179648. View

10.

Jack Jr C, Bernstein M, Borowski B, Gunter J, Fox N, Thompson P . Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative. Alzheimers Dement. 2010; 6(3):212-20. PMC: 2886577. DOI: 10.1016/j.jalz.2010.03.004. View

11.

Imamine R, Kawamura T, Umemura T, Umegaki H, Kawano N, Hotta M . Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes?. Diabetes Res Clin Pract. 2011; 94(1):91-9. DOI: 10.1016/j.diabres.2011.06.014. View

12.

Ott A, Stolk R, Van Harskamp F, Pols H, Hofman A, Breteler M . Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999; 53(9):1937-42. DOI: 10.1212/wnl.53.9.1937. View

13.

Morris J, Vidoni E, Honea R, Burns J . Impaired glycemia increases disease progression in mild cognitive impairment. Neurobiol Aging. 2014; 35(3):585-9. PMC: 3894574. DOI: 10.1016/j.neurobiolaging.2013.09.033. View

14.

Garcia-Casares N, Berthier M, Jorge R, Gonzalez-Alegre P, Gutierrez Cardo A, Rioja Villodres J . Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study. J Alzheimers Dis. 2014; 40(2):375-86. DOI: 10.3233/JAD-131736. View

15.

Risacher S, Kim S, Shen L, Nho K, Foroud T, Green R . The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI). Front Aging Neurosci. 2013; 5:11. PMC: 3612590. DOI: 10.3389/fnagi.2013.00011. View

16.

Saykin A, Shen L, Foroud T, Potkin S, Swaminathan S, Kim S . Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans. Alzheimers Dement. 2010; 6(3):265-73. PMC: 2868595. DOI: 10.1016/j.jalz.2010.03.013. View

17.

Dominguez R, Marschoff E, Gonzalez S, Repetto M, Serra J . Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients. Diabetes Res Clin Pract. 2012; 98(1):68-74. DOI: 10.1016/j.diabres.2012.05.013. View

18.

Baker L, Cross D, Minoshima S, Belongia D, Watson G, Craft S . Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2010; 68(1):51-7. PMC: 3023149. DOI: 10.1001/archneurol.2010.225. View

19.

Roberts R, Knopman D, Cha R, Mielke M, Pankratz V, Boeve B . Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation. J Nucl Med. 2014; 55(5):759-64. PMC: 4011952. DOI: 10.2967/jnumed.113.132647. View

20.

Wang C, Fu K, Liu H, Xing F, Zhang S . Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients: a voxel-based morphometric study. Neural Regen Res. 2014; 9(16):1548-56. PMC: 4192973. DOI: 10.4103/1673-5374.139482. View