Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity

Last, D.; Alsop, David C.; Abduljalil, Amir M.; Marquis, Robert P.; Bazelaire, Cédric de; Hu, Kun; Cavallerano, Jerry D.; Novak, Vera

doi:10.2337/dc06-2052

Cited by 221 publications

(229 citation statements)

References 40 publications

Supporting

Mentioning

208

Contrasting

Unclassified

Order By: Relevance

“…Our result expands previous observations from Doppler (Groschel et al, 2007) and ASL (Last et al, 2007) studies, where decreased response to hypercapnia was found in association with vascular risk factors. Specifically, among all the subjects, both hippocampal and global cortical VR h were affected by vascular risk, corroborating the contribution of impaired vessel function to the damage of brain regions strategic for cognition.…”

Section: Discussionsupporting

confidence: 80%

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

Glodzik

Rusinek

Bryś

et al. 2010

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Vascular risk factors affect cerebral blood flow (CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL = 18, 69.9 ± 6.7 years) and subjects with mild cognitive impairment (MCI = 15, 74.9 ± 8.1 years) were evaluated for the Framingham cardiovascular risk profile (FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL = 17, MCI = 7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (q = À0.41, P = 0.049) and global cortical (q = À0.46, P = 0.02) vasoreactivity to hypercapnia (VR h ). The FCRP-VR h relationships were most pronounced in the MCI group: hippocampus (q = À0.77, P = 0.04); global cortex (q = À0.83, P = 0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VR h was lower in MCI than in NL subjects (Z = À2.0, P = 0.047). This difference persisted after age and FCRP correction (F [3,20] = 4.6, P = 0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VR h is more sensitive to vascular burden than either resting CBF or brain volume.

show abstract

Section: Discussionsupporting

confidence: 80%

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

Glodzik

Rusinek

Bryś

et al. 2010

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…One study reported that patients with diabetic retinopathy, a complication of type 1 diabetes, showed reduced gray matter density in the inferior frontal gyrus and right occipital lobe when compared patients without retinopathy (35). Patients with type 2 diabetes also had 3% less gray matter and ∼17% increase in CSF in the parieto-occipital region (36).…”

Section: Discussionmentioning

confidence: 99%

A commonly carried allele of the obesity-relatedFTOgene is associated with reduced brain volume in the healthy elderly

Stein

Hou

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

231

197

View full text Add to dashboard Cite

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

show abstract

“…Interestingly in patients with type 2 diabetes, regional white matter hyperintensities were associated with reduced cerebrovascular CO 2 responsiveness. 43 Despite the relatively small sample size, further limited by missing NIRS data in 9 patients and 3 controls, the strongly significant decreases in cerebrovascular CO 2 responsiveness in the SCD patients suggest an important role for impaired cerebrovascular CO 2 responsiveness in the increased susceptibility to stroke in SCD, regardless of the presence or absence of silent cerebral infarcts. However, whether silent cerebral infarcts are related to cerebrovascular CO 2 responsiveness, needs to be elucidated in a larger study with cerebrovascular CO 2 responsiveness measurements combined with cerebral MRI.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Nur

Kim

Truijen

et al. 2009

Blood

View full text Add to dashboard Cite

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxidebioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO 2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO 2 responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V mean ), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO 2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO 2 responsiveness was quantified as ⌬% V mean and ⌬mol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO 2 tension. Both ways of measurements revealed lower cerebrovascular CO 2 responsiveness in SCD patients versus controls (V mean , 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 ⌬% V mean per mm Hg, P < .001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 ⌬mol/L per mm Hg, P ‫؍‬ .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 ⌬mol/L per mm Hg, P ‫؍‬ .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 ⌬mol/L per mm Hg, P ‫؍‬ .038). Cerebrovascular CO 2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO 2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke. (Blood. 2009;114:3473-3478) IntroductionCerebral infarction is one of the most devastating complications of sickle cell disease (SCD), occurring in approximately 10% of patients in the first 2 decades of life. 1-3 Furthermore, silent cerebral infarctions occur in approximately 17% of pediatric patients 4,5 and are associated with poor educational and cognitive functioning. 6 SCD is characterized by chronic hemolytic anemia and ongoing vaso-occlusion with exacerbations often requiring medical care. [7][8][9] The vaso-occlusive process in SCD is of a complex nature mediated by red cell and leukocyte adhesion, inflammation, oxidative stress, and a hypercoagulable state, all resulting in endothelial injury and dysfunction. 8 In addition, by reducing the nitric oxide (NO) bioavailability and by damaging the endothelium through the catalyzation of oxidative reactions in endothelial cells, chronic hemolysis leads to vascular complications. [10][11][12] Elevated cerebral blood flow (CBF) velocity (Ն 200 cm/s), measured by transcranial Doppler (TCD), has been identified as a risk factor for stroke in SCD. 13 However, little is known about the mechanism of (ischemic) stroke in SCD patients, and it has not been elucidated whether the increased CBF velocity plays a causative role in stroke or whether it is a result of SCD-related hemodynamic disturbances.CBF is tightly regulated to maintain constancy of cerebral perfusion in the face of various systemic blood pressures by both ...

show abstract

Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity

Cited by 221 publications

References 40 publications

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

A commonly carried allele of the obesity-relatedFTOgene is associated with reduced brain volume in the healthy elderly

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Contact Info

Product

Resources

About