Muhammad Ayaz Khan

White Matter Integrity in Physically Fit Older Adults

BACKGROUND White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. METHODS Ten Masters athletes (3 females, age=72.2 ± 5.3 years, endurance training >15 years) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5 ± 4.3 years) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyperintensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). RESULTS After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=-0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. CONCLUSIONS These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults.

Cerebral hemodynamics in normal aging: central artery stiffness, wave reflection, and pressure pulsatility

Blood ejected from the left ventricle perfuses the brain via central elastic arteries, which stiffen with advancing age and may elevate the risk of end-organ damage. The purpose of this study was to determine the impact of central arterial aging on cerebral hemodynamics. Eighty-three healthy participants aged 22 to 80 years underwent the measurements of cerebral blood flow (CBF) and CBF velocity (CBFV) using magnetic resonance imaging (MRI) and transcranial Doppler, respectively. The CBF pulsatility was determined by the relative amplitude of CBFV to the mean value (CBFV%). Central arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (carotid augmentation index), and pressure were measured using applanation tonometry. Total volume of white-matter hyperintensity (WMH) was quantified from MR images. Total CBF decreased with age while systolic and pulsatile CBFV% increased and diastolic CBFV% decreased. Women showed greater total CBF and lower cerebrovascular resistance than men. Diastolic CBFV% was lower in women than in men. Age- and sex-related differences in CBF pulsatility were independently associated with carotid pulse pressure and arterial wave reflection. In older participants, higher pulsatility of CBF was associated with the greater total volume of WMH. These findings indicate that central arterial aging has an important role in age-related differences in cerebral hemodynamics.

Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment

To determine if global brain hypoperfusion and oxygen hypometabolism occur in patients with amnestic mild cognitive impairment (aMCI).

Vascular Coupling in Resting-State FMRI: Evidence from Multiple Modalities

Resting-state functional magnetic resonance imaging (rs-fMRI) provides a potential to understand intrinsic brain functional connectivity. However, vascular effects in rs-fMRI are still not fully understood. Through multiple modalities, we showed marked vascular signal fluctuations and high-level coupling among arterial pressure, cerebral blood flow (CBF) velocity and brain tissue oxygenation at < 0.08 Hz. These similar spectral power distributions were also observed in blood oxygen level-dependent (BOLD) signals obtained from six representative regions of interest (ROIs). After applying brain global, white-matter, cerebrospinal fluid (CSF) mean signal regressions and low-pass filtering (< 0.08 Hz), the spectral power of BOLD signal was reduced by 55.6% to 64.9% in all ROIs (P = 0.011 to 0.001). The coherence of BOLD signal fluctuations between an ROI pair within a same brain network was reduced by 9.9% to 20.0% (P = 0.004 to < 0.001), but a larger reduction of 22.5% to 37.3% (P = 0.032 to < 0.001) for one not in a same network. Global signal regression overall had the largest impact in reducing spectral power (by 52.2% to 61.7%) and coherence, relative to the other three preprocessing steps. Collectively, these findings raise a critical question of whether a large portion of rs-fMRI signals can be attributed to the vascular effects produced from upstream changes in cerebral hemodynamics.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug‐induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the ‘over‐’ rather than the ‘less‐reactive’ CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure.

Measurement of cerebral blood flow using phase contrast magnetic resonance imaging and duplex ultrasonography

Phase contrast magnetic resonance imaging (PC-MRI) and color-coded duplex ultrasonography (CDUS) are commonly used for measuring cerebral blood flow in the internal carotid (ICA) and vertebral arteries. However, agreement between the two methods has been controversial. Recent development of high spatial and temporal resolution blood vessel wall edge-detection and wall-tracking methods with CDUS increased the accuracy and reliability of blood vessel diameter, hence cerebral blood flow measurement. The aim of this study was to compare the improved CDUS method with 3 T PC-MRI for cerebral blood flow measurements. We found that cerebral blood flow velocity measured in the ICA was lower using PC-MRI than CDUS (left ICA: PC-MRI, 18.0 ± 4.2 vs. CDUS, 25.6 ± 8.6 cm/s; right ICA: PC-MRI, 18.5 ± 4.8 vs. CDUS, 26.6 ± 6.7 cm/s, both p < 0.01). However, ICA diameters measured using PC-MRI were larger (left ICA: PC-MRI, 4.7 ± 0.50 vs. CDUS, 4.1 ± 0.46 mm; right ICA: PC-MRI, 4.5 ± 0.49 vs. CDUS, 4.0 ± 0.45 mm, both p < 0.01). Cerebral blood flow velocity measured in the left vertebral artery with PC-MRI was also lower than CDUS, but no differences in vertebral artery diameter were observed between the methods. Dynamic changes and/or intrinsic physiological fluctuations may have caused these differences in vessel diameter and velocity measurements between the methods. However, estimation of volumetric cerebral blood flow was similar and correlated between the methods despite the presence of large individual differences. These findings support the use of CDUS for cerebral blood flow measurements in the ICA and vertebral artery.