Age, BMI and diabetes as independent predictors of brain hypoperfusion
Abstract
Background: Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction
in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to
cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent
factors that contribute to the appearance of regional brain perfusion changes besides those that are already known.
Material and methods: Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration
of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging
applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state
functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas
space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal
lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS
25 statistical software package, general linear regression analysis, Student’s t-test, and Mann-Whitney U-test were applied for
statistical analyses.
Results: Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and
patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent
significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of
normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the
brain stem (p < 0.01).
Conclusions: Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to
be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and
the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in
metabolic diseases.
Keywords: brain perfusionSPECTtype 2 diabetes mellitusobesityinsulalimbic regionbrain stem
References
- Ishiwata A, Sakayori O, Minoshima S, et al. Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study. Acta Neurologica Scandinavica. 2006; 114(2): 91–96.
- Jagust WJ, Eberling JL, Reed BR, et al. Clinical studies of cerebral blood flow in Alzheimer's disease. Ann N Y Acad Sci. 1997; 826: 254–262.
- Aanerud J, Borghammer P, Chakravarty M, et al. Brain Energy Metabolism and Blood Flow Differences in Healthy Aging. Journal of Cerebral Blood Flow & Metabolism. 2012; 32(7): 1177–1187.
- Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease. J Neurosci Res. 2017; 95(4): 943–972.
- Okonkwo OC, Xu G, Oh JM, et al. Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer's disease. Cereb Cortex. 2014; 24(4): 978–988.
- Catafau A, Lome�a F, Pavia J, et al. Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study. European Journal of Nuclear Medicine. 1996; 23(10): 1329–1337.
- Bouras C, Kövari E, Herrmann F, et al. Stereologic Analysis of Microvascular Morphology in the Elderly. Journal of Neuropathology and Experimental Neurology. 2006; 65(3): 235–244.
- Jeynes B, Provias J. The possible role of capillary cerebral amyloid angiopathy in Alzheimer lesion development: a regional comparison. Acta Neuropathol. 2006; 112(4): 417–427.
- Kövari E, Gold G, Herrmann F, et al. Cortical Microinfarcts and Demyelination Significantly Affect Cognition in Brain Aging. Stroke. 2004; 35(2): 410–414.
- Kövari E, Gold G, Herrmann FR, et al. Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology. 2007; 68(12): 927–931.
- Gold G, Kövari E, Herrmann F, et al. Cognitive Consequences of Thalamic, Basal Ganglia, and Deep White Matter Lacunes in Brain Aging and Dementia. Stroke. 2005; 36(6): 1184–1188.
- Thal DR, Capetillo-Zarate E, Larionov S, et al. Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances. Neurobiol Aging. 2009; 30(12): 1936–1948.
- Hallam K, Li Q, Ananthakrishnan R, et al. Aldose Reductase and AGE-RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats. Aging Cell. 2010; 9(5): 776–784.
- Biessels G, Strachan M, Visseren F, et al. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. The Lancet Diabetes & Endocrinology. 2014; 2(3): 246–255.
- Solfrizzi V, Scafato E, Capurso C, et al. Italian Longitudinal Study on Aging Working Group. Metabolic syndrome, mild cognitive impairment, and progression to dementia. The Italian Longitudinal Study on Aging. Neurobiol Aging. 2011; 32(11): 1932–1941.
- Birdsill AC, Carlsson CM, Willette AA, et al. Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity (Silver Spring). 2013; 21(7): 1313–1320.
- Cui Y, Liang X, Gu H, et al. Cerebral perfusion alterations in type 2 diabetes and its relation to insulin resistance and cognitive dysfunction. Brain Imaging Behav. 2017; 11(5): 1248–1257.
- Willeumier K, Taylor D, Amen D. Elevated BMI Is Associated With Decreased Blood Flow in the Prefrontal Cortex Using SPECT Imaging in Healthy Adults. Obesity. 2012; 19(5): 1095–1097.
- Avants BB, Tustison N, Song G. Advanced normalization tools (ANTS). Insight J. 2009; 2(365): 1–35.
- Jansen JFA, van Bussel FCG, van de Haar HJ, et al. Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus. Sci Rep. 2016; 6(1): 10.
- Bonthius D, Solodkin A, Hoesen GV. Pathology of the Insular Cortex in Alzheimer Disease Depends on Cortical Architecture. Journal of Neuropathology and Experimental Neurology. 2005; 64(10): 910–922.
- HUNT L, SELVARAJAH D, TESFAYE S, et al. Cerebral Blood Flow Abnormalities in Brain Regions Responsible for Cognitive Function in Type 2 Diabetes. Diabetes. 2018; 67(Supplement 1).
- Toda N, Ayajiki K, Okamura T. Obesity-induced cerebral hypoperfusion derived from endothelial dysfunction: one of the risk factors for Alzheimer's disease. Curr Alzheimer Res. 2014; 11(8): 733–744.
- Torre JCd, Pappas BA, Prevot V, et al. Hippocampal nitric oxide upregulation precedes memory loss and Aβ1-40accumulation after chronic brain hypoperfusion in rats. Neurological Research. 2013; 25(6): 635–641.
- Gunstad J, Paul RH, Cohen RA, et al. Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry. 2007; 48(1): 57–61.
- Gustafson D, Lissner L, Bengtsson C, et al. A 24-year follow-up of body mass index and cerebral atrophy. Neurology. 2004; 63(10): 1876–1881.
- Livingston JM, McDonald MW, Gagnon T, et al. Influence of metabolic syndrome on cerebral perfusion and cognition. Neurobiol Dis. 2020; 137: 104756.
- Sabri O, Hellwig D, Schreckenberger M, et al. Influence of diabetes mellitus on regional cerebral glucose metabolism and regional cerebral blood flow. Nucl Med Commun. 2000; 21(1): 19–29.
