Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study.
Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline.
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia; School of Psychology, University of Birmingham, Edgbaston B152TT, UK.
Amanda G
AG
Wood
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia; Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, VIC 3052, Australia.
Jian
J
Chen
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia.
Christopher
C
Moran
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia.
Thanh
T
Phan
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia; Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, VIC 3052, Australia.
Richard
R
Beare
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia.
Kimberley
K
Cooper
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia.
Stacey
S
Litras
Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC 3168, Australia; Menzies Research Institute, Hobart, TAS 7000, Australia.
Velandai
V
Srikanth
D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D014429:Twins, Dizygotic / Q000523:psychology; D014430:Twins, Monozygotic / Q000523:psychology