Person:

Novak, Vera

OBJECTIVE—The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation.

RESEARCH DESIGN AND METHODS—CBF was examined in 26 diabetic (aged 61.6 ± 6.6 years) and 25 control (aged 60.4 ± 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla.

RESULTS—The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (−13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (−3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region.

CONCLUSIONS—Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.

Hypertension is associated with microvascular and macrovascular brain injury but its direct influence on the cerebral circulation is not fully clear. Our objective was to investigate the association of hypertension with global and regional cerebral vasoreactvity to CO2 using continuous arterial spin labeling magnetic resonance imaging, independent of stroke and white matter hyperintensities. Participants (n=62; mean age 66.7±1.0 years, 55% women, 84% white, 65% hypertension, 47% stroke) underwent arterial spin labeling perfusion MRI during normal breathing, 5% CO2 rebreathing, and hyperventilation as well as 24-hour ambulatory blood pressure monitoring. Vasoreactivity was the slope of the regression between cerebral perfusion and end-tidal CO2. White matter hyperintensity volumes were quantified. Nighttime dipping was calculated as the percent decline in nighttime/daytime blood pressure. After accounting for stroke and white matter hyperintensity volume, hypertensive participants had lower global vasoreactivity (1.11±0.13 vs. 0.43±0.1 ml/100gm/min/mmHg, p= 0.0012). Regionally, this was significant in the frontal, temporal and parietal lobes. Higher mean systolic blood pressure was associated with lower vasoreactivity (decreased by 0.11 units/10 mm Hg increase in systolic blood pressure, p=0.04), but nighttime dipping was not (p=0.2). The magnitude of decrease in vasoreactivity in hypertension without stroke was comparable to the magnitude of decrease in vasoreactivity in stroke without hypertension. Hypertension has a direct negative effect on the cerebrovascular circulation independent of white matter hyperintensities and stroke that is comparable to that seen with stroke. Since lower vasoreactivity is associated with poor outcomes, studies of the impact of antihypertensive on vasoreactivity are important.

OBJECTIVE Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs.

RESEARCH DESIGN AND METHODS We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 ± 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO2 rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI.

RESULTS The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO2 reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA1c (A1C), and inflammatory markers and positively associated with systolic blood pressure (R2 = 0.86, P < 0.0001).

CONCLUSIONS Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.

Background Although blood pressure elevation and lower nocturnal dipping both increase vascular risk, it is not known if either or both are also associated with brain atrophy, cerebral perfusion, and functional status.

Methods We investigated the association of elevated blood pressure and nocturnal dipping based on 24-hour ambulatory recordings with brain atrophy and perfusion and functional status in 80 older adults with and without stroke (age 66.4±0.8 years, 51% women, 16% non-white, 46% prior ischemic stroke, 55% hypertension). Anatomical and 3-D continuous arterial spin labeling brain MRI measuring volumes and perfusion and 24-h ambulatory blood pressure readings were completed.

Results Nocturnal dipping of lesser magnitude in systolic (non-stroke: p=0.03; stroke: p=0.005) and pulse pressure (non-stroke: p=0.002; stroke: p=0.01) was associated with greater brain atrophy, affecting preferentially the fronto-parietal regions. Dipping of lesser magnitude in systolic blood pressure (non-stroke: p=0.01; stroke: p=0.03) and greater brain atrophy (non-stroke: p=0.04; stroke: p= 0.05) were also associated with slower gait speed and worse functional outcome post stroke. Higher 24-hour blood pressure averages were associated with lower cerebral perfusion but not atrophy in those with and without stroke.

Conclusions In those with and without stroke, dipping of lesser magnitude in systolic and pulse pressure is associated with brain atrophy and worse functional status. Nocturnal dipping, in addition to elevated blood pressure, should be considered as an additional important target in the clinical evaluation of those at risk for cerebrovascular disease or functional loss.

Background White matter hyperintensities (WMHs) on MRI have been associated with age, cardiovascular risk factors and falls in the elderly. This study evaluated the relationship between WMHs and dynamics of postural control in older adults without history of falls.

Methods We studied 76 community-living subjects without history of falls (age 64.5±7.3 years). Brain and WMH volume calculations and clinical rating were done on fluid-attenuation inversion recovery (FLAIR) and MP-RAGE MR images on 3 T. Balance was assessed from the center of pressure displacement using the force platform during 3 min of quiet standing using traditional and dynamic measures (using stabilogram-diffusion analysis). Gait speed was measured from 12-min walk.

Results Age-adjusted periventricular and focal WMHs were associated with changes in certain dynamic balance measures, including reduced range of postural sway in anteroposterior direction (fronto-temporal WMHs, P=.045; parieto-occipital WMHs, P=.009) and more irregular long-term mediolateral fluctuations (P=.046). Normal walking speed was not affected by WMHs.

Conclusions Periventricular and focal WMHs affect long-term dynamics of postural control, which requires engagement of feedback mechanisms, and may contribute to mobility decline in the elderly.