Jiabao He

Visual cortex in dementia with Lewy bodies: magnetic resonance imaging study

Background Visual hallucinations and visuoperceptual deficits are common in dementia with Lewy bodies, suggesting that cortical visual function may be abnormal. Aims To investigate: (1) cortical visual function using functional magnetic resonance imaging (fMRI); and (2) the nature and severity of perfusion deficits in visual areas using arterial spin labelling (ASL)-MRI. Method In total, 17 participants with dementia with Lewy bodies (DLB group) and 19 similarly aged controls were presented with simple visual stimuli (checkerboard, moving dots, and objects) during fMRI and subsequently underwent ASL-MRI (DLB group n = 15, control group n = 19). Results Functional activations were evident in visual areas in both the DLB and control groups in response to checkerboard and objects stimuli but reduced visual area V5/MT (middle temporal) activation occurred in the DLB group in response to motion stimuli. Posterior cortical perfusion deficits occurred in the DLB group, particularly in higher visual areas. Conclusions Higher visual areas, particularly occipito-parietal, appear abnormal in dementia with Lewy bodies, while there is a preservation of function in lower visual areas (V1 and V2/3).

Characterizing dementia with Lewy bodies by means of diffusion tensor imaging

Objective: To investigate patterns of in vivo white matter tract change using diffusion tensor imaging (DTI), we conducted a cross-sectional study of dementia with Lewy bodies (DLB) in comparison with Alzheimer disease (AD) and normal aging. Methods: The study included 106 subjects (35 with DLB, 36 with AD, and 35 elderly controls) who underwent clinical and neuropsychological assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate patterns of reduced fractional anisotropy (FA) and increased mean diffusivity (MD) across the entire white matter tract skeleton and also investigated correlations with clinical features. Results: Areas of reduced FA in subjects with DLB vs controls were found primarily in parieto-occipital white matter tracts; in AD, the changes were much more diffuse. DLB was also associated with reduced FA in the pons and left thalamus, in comparison with AD. The pattern of MD increase was diffuse in AD and DLB. We found an association between DTI parameters and impaired episodic memory, letter fluency, and severity of motor parkinsonism in DLB. Conclusions: Despite a similar level of dementia severity, patterns of DTI changes in AD and DLB differed significantly. The selective involvement of the visual association areas and subcortical structures and the significant clinical correlations highlight the potential importance of white matter tract change in the pathogenesis of DLB. DTI may be a useful technique to investigate early and possible preclinical changes in DLB and warrants further investigation.

White matter correlates of cognitive dysfunction after mild traumatic brain injury

Objective: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation. Methods: Fifty-three patients were scanned an average of 6 days postinjury (range = 1–14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance. Results: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps. Conclusions: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.

Cerebral blood flow by arterial spin labeling in poststroke dementia

Objective: To investigate the relationship between cerebral blood flow and dementia in older stroke survivors and subjects with Alzheimer disease (AD). Methods: This cohort study used arterial spin labeling MRI at 3 T to examine cerebral blood flow (CBF). We scanned 39 patients 6 years after stroke. They were older than 75 years at the time of stroke and free of dementia 3 months poststroke, with 8 subsequently developing dementia. We also scanned 17 subjects with AD and 29 healthy control subjects. We determined the perfusion in regions of interest (ROIs). Hippocampal volume was also measured using a previously validated automated procedure. Results: The gray matter/white matter CBF ratio was reduced globally in the poststroke dementia (PSD) group (1.55 SD = 0.12) relative to control subjects (1.78 SD = 0.18; p = 0.03). The CBF ratio in a parietal ROI was reduced in the AD (1.34 SD = 0.31; p = 0.003), PSD (1.32 SD = 0.22; p = 0.041), and poststroke no-dementia (PSND) (1.44 SD = 0.34; p = 0.014) groups relative to that of control subjects (1.70 SD = 0.32). In subjects without stroke, the best predictor of dementia was hippocampus volume, whereas in the stroke group, it was the global CBF gray matter/white matter ratio. Hippocampus volume was not significantly different between the AD and PSD groups, and both had reduced hippocampi relative to those of control subjects and the PSND group. Conclusions: We found evidence for both vascular and AD pathology in PSD, suggesting that both the direct impact of the stroke and subsequent development of AD-type changes play a role in the etiology of PSD.

Effects of Community Exercise Therapy on Metabolic, Brain, Physical, and Cognitive Function Following Stroke A Randomized Controlled Pilot Trial

Background. Exercise therapy could potentially modify metabolic risk factors and brain physiology alongside improving function post stroke. Objective. To explore the short-term metabolic, brain, cognitive, and functional effects of exercise following stroke. Methods. A total of 40 participants (>50 years, >6 months post stroke, independently mobile) were recruited to a single-blind, parallel, randomized controlled trial of community-based exercise (19 weeks, 3 times/wk, “exercise” group) or stretching (“control” group). Primary outcome measures were glucose control and cerebral blood flow. Secondary outcome measures were cardiorespiratory fitness, blood pressure, lipid profile, body composition, cerebral tissue atrophy and regional brain metabolism, and physical and cognitive function. Results. Exercise did not change glucose control (homeostasis model assessment 1·5 ± 0·8 to 1·5 ± 0·7 vs 1·6 ± 0·8 to 1·7 ± 0·7, P = .97; CI = −0·5 to 0·49). Medial temporal lobe tissue blood flow increased with exercise (38 ± 8 to 42 ± 10 mL/100 g/min; P < .05; CI = 9.0 to 0.1) without any change in gray matter tissue volume. There was no change in medial temporal lobe tissue blood flow in the control group (41 ± 8 to 40 ± 7 mL/100 g/min; P = .13; CI = −3.6 to 6.7) but significant gray matter atrophy. Cardiorespiratory fitness, diastolic blood pressure, high-density lipoprotein cholesterol, physical function, and cognition also improved with exercise. Conclusion. Exercise therapy improves short-term metabolic, brain, physical, and cognitive function, without changes in glucose control following stroke. The long-term impact of exercise on stroke recurrence, cardiovascular health, and disability should now be explored.

Intensive Blood Pressure Lowering Increases Cerebral Blood Flow in Older Subjects With Hypertension

Hypertension is associated with reduced cerebral blood flow (CBF). Intensive (<130/80 mm Hg) blood pressure (BP) lowering in older people might give greater reduction in cardiovascular risk, but there are concerns that this might produce hypoperfusion which may precipitate falls and possibly stroke. We determined the effect of intensive compared with usual BP lowering on CBF in hypertensive older subjects. Individuals aged >70 years with a history of systolic hypertension on 1 or no BP lowering drugs were recruited from primary care (n=37; age, 75±4 years; systolic BP, >150 mm Hg) and randomized to receive intensive (target BP, <130/80 mm Hg) or usual (target BP, <140/85 mm Hg) BP lowering for 12 weeks, with reviews every 2 weeks. CBF, determined using 3T arterial spin labeling MRI, and 24-hour ambulatory BP were performed at baseline and after 12 weeks of treatment. Baseline BP (ambulatory or in clinic) and baseline gray matter CBF were not significantly different between the groups. After treatment, BP was reduced significantly in both groups but fell more in the intensive group (26/17 versus 15/5 mm Hg; P<0.01). Over the same period, gray matter CBF increased significantly in the intensive group (7±11 mL/min per 100 g; P=0.013) but was unchanged in the usual BP target group (−3±9 mL/min per 100 g; P=0.23); P<0.01 for comparison. Intensive BP lowering in older people with hypertension increases CBF, compared with BP lowering to usual target. These findings suggest hypertension in older people shifts the autoregulatory CBF curve rightward and downward and is reversible with BP lowering.

Blood Pressure Lowering and Cerebral Blood Flow:Intensive Blood Pressure Lowering Increases Cerebral Blood Flow in Older Subjects With Hypertension

Hypertension is associated with reduced cerebral blood flow (CBF). Intensive (<130/80 mm Hg) blood pressure (BP) lowering in older people might give greater reduction in cardiovascular risk, but there are concerns that this might produce hypoperfusion which may precipitate falls and possibly stroke. We determined the effect of intensive compared with usual BP lowering on CBF in hypertensive older subjects. Individuals aged >70 years with a history of systolic hypertension on 1 or no BP lowering drugs were recruited from primary care (n=37; age, 75±4 years; systolic BP, >150 mm Hg) and randomized to receive intensive (target BP, <130/80 mm Hg) or usual (target BP, <140/85 mm Hg) BP lowering for 12 weeks, with reviews every 2 weeks. CBF, determined using 3T arterial spin labeling MRI, and 24-hour ambulatory BP were performed at baseline and after 12 weeks of treatment. Baseline BP (ambulatory or in clinic) and baseline gray matter CBF were not significantly different between the groups. After treatment, BP was reduced significantly in both groups but fell more in the intensive group (26/17 versus 15/5 mm Hg; P<0.01). Over the same period, gray matter CBF increased significantly in the intensive group (7±11 mL/min per 100 g; P=0.013) but was unchanged in the usual BP target group (−3±9 mL/min per 100 g; P=0.23); P<0.01 for comparison. Intensive BP lowering in older people with hypertension increases CBF, compared with BP lowering to usual target. These findings suggest hypertension in older people shifts the autoregulatory CBF curve rightward and downward and is reversible with BP lowering.

Disease activity and cognition in rheumatoid arthritis: an open label pilot study

IntroductionWe hypothesised that fatigue in rheumatoid arthritis (RA) is related to TNF-alpha induced dysregulation of cerebral blood flow. Our objectives were to assess fatigue, cognitive function and cerebral blood flow before and after initiation of anti-TNF treatment.MethodsIn a pilot study, 15 patients initiating treatment with adalimumab were assessed for fatigue using a visual analogue scale (FACIT-F), cognitive function using a panel of psychometric tests and regional cerebral blood flow using MR perfusion imaging.ResultsPatients improved clinically after anti-TNF therapy in terms of DAS28 and FACIT-F. Furthermore significant improvements were documented in full scale, verbal and performance IQ following therapy. There was a non-significant trend towards reduced cerebral perfusion in both grey and white matter, and fatigue at 3 months correlated with cerebral blood flow in white (p = 0.014) and grey (p = 0.005) matter.ConclusionsWe demonstrate for the first time a significant improvement in cognitive function following effective treatment of RA. Although we observed minor reductions in cerebral blood flow, and a correlation between cerebral blood flow and fatigue, a larger, controlled study would be required to affirm a causal relationship.

Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation

Cerebral blood flow (CBF) is maintained despite changing systemic blood pressure through cerebral vascular control, with such tight regulation believed to be under local tissue control. Chronic fatigue syndrome (CFS) associates with a wide range of symptoms, including orthostatic intolerance, skeletal muscle pH abnormalities and cognitive impairment. CFS patients are known to have reduced CBF and orthostatic intolerance associates with abnormal vascular regulation, while skeletal muscle pH abnormalities associate with autonomic dysfunction. These findings point to autonomic dysfunction as the central feature of CFS, and cerebral vascular control being influenced by factors outside of the brain, a macroscopic force affecting the stability of regional regulation. We therefore explored whether there was a physiological link between cerebral vascular control and skeletal muscle pH management in CFS. Seventeen consecutive CFS patients fulfilling the Fukuda criteria were recruited from our local CFS clinical service. To probe the static scenario, CBF and skeletal muscle pH were measured at rest using MRI and 31P magnetic resonance spectroscopy (31P-MRS). To examine dynamic control, brain functional MRI was performed concurrently with Valsalva manoeuvre (VM), a standard autonomic function challenge, while 31P-MRS was performed during plantar flexion exercise. Significant inverse correlation was seen between CBF and skeletal muscle pH at rest (r = − 0.67, p < 0.01). Prolonged cerebral vascular constriction during the sympathetic phase of VM was associated with higher pH in skeletal muscle after plantar flexion exercise (r = 0.69, p < 0.008). In conclusion, cerebral vascular control is closely related to skeletal muscle pH both at rest and after dynamic stimulation in CFS.

Comparative study of standard space and real space analysis of quantitative MR brain data

To compare the robustness of region of interest (ROI) analysis of magnetic resonance imaging (MRI) brain data in real space with analysis in standard space and to test the hypothesis that standard space image analysis introduces more partial volume effect errors compared to analysis of the same dataset in real space.