Siegbert Warkentin

Sex Differences in Regional Cerebral Blood Flow

Regional cerebral blood flow was measured by the 133-xenon inhalation method during resting in 38 healthy men and 38 healthy women matched pairwise for age in the range 18–72 years. The results showed 11% higher global flow level in the women in all ages. A similar and significant regression of flow by age was seen for both sexes. The regional flow distribution also showed some sex-related differences. Frontal regions showed an asymmetry in the men with higher values on the right side. The female flows were more symmetric. As a hypothesis, it is suggested that the higher flow level in women may be a systemic phenomenon. In fact, other authors have found a higher cardiac index in females. The sex differences in regional flow pattern might be due to differences in the functional organization of the cortex and/or to differences in the mental processes of the “resting” state.

Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease.

It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer’s disease (AD). We measured the levels of α1-antichymotrypsin (ACT), α1-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.

Regional cerebral blood flow in long-term heavy cannabis use

Regional cerebral blood flow (rCBF) was measured by the 133Xenon inhalation method in nine male chronic cannabis users. The rCBF level in cannabis users was significantly (11%) lower than that of age- and sex-matched healthy controls. Four of the subjects were reexamined after 9-60 days of detoxification and showed a significant (12%) increase of the CBF level at followup. No significant regional flow abnormalities were noted. The global CBF reduction seen in the early phase of detoxification is most likely the consequence of the dysfunction of the central nervous system accompanying chronic cannabis use.

Frontal lobe dysfunction in long-term cannabis users

This study examined the neurophysiological effects of cannabis. Cerebral blood flow (CBF) was measured in 12 long-term cannabis users shortly after cessation of cannabis use (mean 1.6 days). The findings showed significantly lower mean hemispheric blood flow values and significantly lower frontal values in the cannabis subjects compared to normal controls. The results suggest that the functional level of the frontal lobes is affected by long-term cannabis use.

Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

This study aimed to identify preclinical Alzheimers disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments ((133)Xe method) were performed in 70 patients with MCI who were cognitively stable for 4-6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for beta-amyloid(1-42), total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P<0.0001). Subjects with pathological levels of both CSF tau and beta-amyloid(1-42) were also at high risk of developing AD (hazard ratio 13.4, P<0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 (P<0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.

Orthostatic hypotension in organic dementia: relationship between blood pressure, cortical blood flow and symptoms

Regional cerebral blood flow was measured in 35 patients with organic dementia (Alzheimers disease, n=13, vascular dementia, n=17, frontotemporal dementia, n=5) and orthostatic hypotension. Measurements were performed during supine rest and during head-up tilt (60°). Despite marked blood pressure falls, few patients had symptoms of orthostatic hypotension. All three dementia groups had a decrease in regional cerebral blood flow in the frontal lobes during head-up tilt, but no change in mean hemispheric flow. All patients had a consistent drop in their systolic blood pressure upon head-up tilt, with a wide variation over time. The findings suggest that orthostatic hypotension needs to be considered, and actively sought for, in organic dementia as many patients may lack the typical symptoms of orthostatic hypotension, despite a marked fall in blood pressure.

Functional imaging of the frontal lobes in organic dementia. Regional cerebral blood flow findings in normals, in patients with frontotemporal dementia and in patients with Alzheimer's disease, performing a word fluency test

Patterns of functional cortical activation were studied by means of regional cerebral blood flow measurements, performed during rest and during a word fluency task in normal subjects (n = 22), in patients with Alzheimers disease (n = 17), and in patients with frontotemporal dementia (n = 15). Although all groups showed a significant activation of the Brocas area during word production, the activation of the dorsolateral prefrontal cortex was clearly subnormal in both dementia groups. The frontal dysfunction was not explained by number of words produced, illness duration, or age. Thus, the results demonstrate that the word fluency task is a sensitive measure of frontal lobe function, and its incorporation in imaging studies may facilitate the detection of subtle functional impairment of the frontal lobes in organic dementia.

Regional patterns of cortical blood flow distinguish extraverts from introverts

Summary-Eysenck’s hypothesis of higher cortical arousal in introverts was examined using regional cerebral blood flow measurement in 37 healthy subjects. The measurement was made at rest. using the “)Xe-inhalation method. Estimates of gray matter flow were obtained for 32 brain regions. There was no significant evidence of personality differences in general arousal, as measured by the mean flow level, averaged over all regions. There were. however, regional differences. An overall test of the blood flow distribution indicated different patterns of activity in introverts and extraverts. Follow-up tests attributed this to higher flow in the temporal lobes for introverts than for extraverts. Higher temporal lobe activity in introverts may be interpreted as increased functional connections between cortex and the limbic system. Related findings of personality alterations in temporal lobe epilepsy and the Kliiver-Bucy syndrome support this contention.

Multiple rapid automatic naming measures of cognition: Normal performance and effects of aging

Rapid automatic naming tasks are clinical tools for probing brain functions that underlie normal cognition. To compare performance for various stimuli in normal subjects and assess the effect of aging, we administered six single-dimension stimuli (color, form, number, letter, animal, and object) and five dual-dimension stimuli (color-form, color-number, color-letter, color-animal, and color-object) to 144 normal volunteers who ranged in age from 15 to 85 years. Rapid automatic naming times for letters and numbers were significantly less than for forms, animals, and objects. Rapid automatic naming times for color-number and color-letter stimuli were significantly less than for color-form, color-animal, or color-object stimuli. Age correlated significantly with rapid automatic naming time for each single-dimension stimulus and for color-form, color-number, color-animal, and color-object stimuli. Linear regression showed that rapid automatic naming times increased with age for aggregated color stimuli, aggregated single-dimension stimuli, and aggregated dual-dimension stimuli. This age effect persisted in subgroups less than 60 years of age and greater than 60 years of age. We conclude that normal performance time is dependent on the task, with letter and number stimuli eliciting most rapid responses, and that most rapid automatic naming times increase with age.

Cycloid psychosis: regional cerebral blood flow correlates of a psychotic episode

Eight patients meeting Leonhards criteria for cycloid psychosis were investigated on repeated occasions during a psychotic episode, with regional cerebral blood flow measurements and clinical ratings. The results showed that, at admission to the hospital, when the patients were clinically exacerbated, the mean hemispheric blood flow was significantly elevated compared with values from a normal control group. The hemispheric blood flow level covaried significantly with the degree of clinical symptoms, such that the more elevated the cortical blood flow was, the more behaviorally disturbed was the patient. At discharge from the hospital, the patients had no residual symptoms and the cortical blood flow was normal. These findings differ distinctly from those commonly made in other psychoses, such as schizophrenia.