John Stirling Meyer

Regional cerebral hemodynamics during migraine and cluster headaches measured by the 133Xe inhalation method.

SYNOPSIS

Is Mild Cognitive Impairment Prodromal for Vascular Dementia Like Alzheimer’s Disease?

Background and Purpose Individuals with mild cognitive impairment (MCI) are at increased risk of Alzheimer’s disease (AD) and probably other forms of dementia. Some subtypes of vascular dementia (VaD) may possess minor neuropathological changes of AD that may contribute to cognitive impairments. It was posited that MCI, identified by criteria described here, might present as a prodrome for VaD and AD. Methods— Serial Mini-Mental State Examination was administered at 3- to 6-month intervals, and neuroimaging was performed annually. Subtle cognitive dysfunctions were weighted and measured according to MCI criteria defined here. Subjects identified with MCI were then followed up for an additional 3.88±3.01 years. Diagnoses of VaD and AD were made according to established criteria. Results— During 3.72±2.94 years of follow-up of the original normative subjects, 73 of 291 (25.1%) developed MCI. Of the 27 subjects who developed VaD, 15 (55.6%) had prodromal MCI. Of these, two thirds were subclassified as having small-vessel dementia. The remaining 12 patients with VaD (44.4%) were diagnosed directly from a cognitively normal status without preceding MCI. These were predominantly multi-infarct or strategic-infarct dementia (66.7%). An additional 35 MCI subjects (47.9%) developed AD. Both VaD and AD diagnosed after MCI prodromes manifested similar spectral domains of cognitive impairments, which included memory, during their MCI stages. Conclusions— In some VaD subtypes, particularly those caused by subcortical microvascular disease, dementia may be preceded by MCI, which has similar domains of cognitive impairment and a similar progressive course that may mimic AD.

Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia

Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT, densitometry, perfusions, and cognitive testing among neurologically and cognitively normative aging volunteers. A total of 224 normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59.5 +/- 15.8 years. Mean follow-up is 5.8 +/- 3.3 years. At follow-up, 22 developed mild cognitive impairment (41 CCSE >/= -3), 19 became demented-8 with Vascular type (VAD), 11 with Alzheimers type (DAT)-and 183 remain cognitively unchanged. Cerebral atrophy, tissue densities, and perfusions were measured by Xe-CT. After age 60, cerebral atrophy, ventricular enlargement, and polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis, and leuko-araiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, and male gender. At age 71.5 +/- 11.9, mild cognitive impairment began accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with VAD. Excessive cortical perfusional decrease, gray and white matter hypodensities, and cerebral atrophy correlate with cognitive decline.

Impaired Neurogenic Cerebrovascular Control and Dysautoregulation After Stroke

Cerebral autoregulation was tested in 32 patients with various anatomical locations and stages of ischemic cerebrovascular disease. Cerebral perfusion pressure (CPP) was raised or lowered in a standard manner by the use of head-up tilting (induced hypotension) and head-down tilting (induced hypertension). Any impairment of cerebral autoregulation was analyzed quantitatively by the ratio of the change in cerebral blood flow (CBF) over the change in CPP. There was significant correlation between the degree of dysautoregulation whether CPP was increased or decreased. An inverse correlation was shown between the degree of dysautoregulation and the duration after the ischemic episode during both induced hypotension and hypertension. Patients with brainstem lesions including those with transient ischemic attacks (TIAs) showed a greater impairment of autoregulation which persisted longer than those with hemispheric lesions. Patients with severe cerebral hemispheric infarction showed greater impairment of autoregulation than those with minor hemispheric lesions. Dysautoregulation also was greater in patients with subcortical lesions compared to those with cortical lesions. Hypertensive patients showed significantly greater decreases in CBF and effective MABP during induced hypotension than normotensive patients although autoregulation index was the same. Thus, symptoms are more frequent in hypertensives because of greater changes in CPP. Paradoxical responses in CBF to changes in CPP occurred in six patients. These were noted in moderately severe lesions in relatively young patients with hypertension and deeply located cerebral or brainstem lesions in the subacute stage. The mechanisms which control cerebral autoregulation were discussed and the nervous structures situated in the deep cerebral regions and brainstem, possibly the central structures of the autonomic nervous system, were proposed to control autoregulation of CBF.

Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers.

Mapping local blood flow of human brain by CT scanning during stable xenon inhalation.

Non-invasive methods are described for estimating local cerebral blood flows (LCBF) and partition coefficients (Lλ) during inhalation of 35% stable xenon gas (Xea) in oxygen during CT scanning. After denitrogenatioD by 100% oxygen breathing, 35% Xe5 is breathed for 7-8 minutes to minimize subanestbetic effects. Mean changes in brain Hounsfleld units extrapolated to 15 minutes were 7.7 units for white matter and S3 units for gray matter. They were measured from volumes 80 cubic mm (10 mm2 area X 8 mm), or larger with an EMI 1010 scanner at 1 minute intervals. These data were used for computing LCBFs and Lλs. Irradiation measured at the center of brain slices was 1 rad per minute. To calculate Lλs about 6 exposures are necessary, thereafter, each 1 minute scan provides LCBF measurements for 2 adjacent 8 mm slices. ReproducibUity for LCBF was r = 0.85 (P < 0.001). Mean Lλs were 0.86 ± 0.08 for gray and 134 ± 0.10 for white matter. Normative mean flows (mls/100 g brain/min) were: basal ganglia = 79.6 ± 93, cortex = 82.3 ± 8.5, white matter = 29.2 ± 5.9, mldbrain tegmentum = 943 ± 14.8, cerebellar cortex = 80.1 ± 10.9, dorsal poos = 89.3 ± 4.7, brachium ponds = 35.0 ± 4.2. Subject finger exercises produced increases of LCBF in contralateral pre-central and post-central gyri. Eye closure decreased flow values limited to the visual system. Gray matter flow values diffusely decreased in non-REM sleep but increased above normal in REM sleep. Cerebral infarction and hemorrhage resulted hi zones of zero flow with borders having reduced Xs and low flows attributed to edema. Stroke, Vol 12, No 4, 1981

Improved method for noninvasive measurement of regional cerebral blood flow by 133Xenon inhalation. Part I: description of method and normal values obtained in healthy volunteers.

A clinical method for noninvasive measurement of regional cerebral blood flow (rCBF) and blood volume (rCBV) is described, basedon Obrists 10 minute, desaturation method after 1 minute inhalationof 133Xe. Sixteen collimated probes are placed over both hemispheres and brain stem-cerebellar regions. End-tidal 18>Xe curves are used for correction of recirculation. KEV discriminators are set to record gamma and x-ray activity separately. Values are printed out automatically by a computer on a brain map. Extracerebral contamination is reduced by 1) computing curves from gamma activity, 2) applying pressure on the scalp beneath the probes, 3) 1 minute inhalation of 133Xe and recording desaturation curves for 10 minutes, thereby minimizing slow clearance from extracranial tissues. Normal values for both fast and slow compartments are reproducible and are in good agreement with the carotid injection method. The speech dominant hemisphere has higher flow than the right under conditions described. Posterior portions of the cranium over the cerebellum andbrain stem appear to have higher flow gray values than the cerebral cortex. Gray matter flow decreases with advancing age.

White matter lesion in the elderly

Abstract The advent of neuroimaging has brought medical attention to the frequency of unsuspected white matter lesions in the brains of elderly people. In 1987 Hackinski suggested the term “leuko-araiosis” to identify such white matter abnormalities detected by computed tomography and magnetic resonance imaging to emphasize that their etiology and clinical relevance require clarification. Since then, leuko-araiosis has been recognized among approximately ten percent of apparently normal, elderly people over age sixtyfive. The severity and frequency of leuko-araiosis increases with advancing age, risk factors for stroke, history of strokes particularly of the lacunar type and dementia of both the vascular and Alzheimer type. Current concepts concerning the pathogenesis and neurological concomitants of leuko-araiosis are reviewed. The etiology of leuko-araiosis may be heterogeneous but is most likely ischemic in nature. However, as white matter lesions progress among the elderly they are likely to become associated with cognitive impairments and motor dyspraxias presumably resulting from cortico-subcortical disconnections, particularly involving the frontal cortex and basal ganglia and may themselves be considered a radiological “risk factor” or precursor for dementia.

Cardiovascular and Other Risk Factors for Alzheimer's Disease and Vascular Dementia

Abstract: Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risks accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions, and cognitive testing among 224 neurologically and cognitively normative aging volunteers. After age 60, cerebral atrophy, ventricular enlargement, polioaraiosis, and leukoaraiosis geometrically increased as perfusions declined. Risks accelerating perfusional decline, cerebral atrophy, polioaraiosis, and leukoaraiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5 ± 11.9, subtle cognitive decline began, accelerated by TIAs, hypertension, and heart disease. Leukoaraiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with vasciular dementias. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with Alzheimers disease. We concluded that TIAs, hypertension, hyperlipidemia, smoking, and male gender accelerate cerebral degenerative changes, cognitive decline, and dementia.

Leukoaraiosis correlates with cerebral hypoperfusion in vascular dementia.

Leukoaraiosis quantified by computerized densitometric measurements of reduced Hounsfield numbers was correlated with local cerebral blood flow on the same computed tomographic images of 35 patients with multi-infarct dementia and 16 age-matched elderly normal volunteers. The ratio for area of frontal leukoaraiosis to total area of parenchyma among the patients was significantly greater than that among the normal volunteers (5.8 +/- 2.3% compared with 3.1 +/- 1.3%, p less than 0.001). Severity of leukoaraiosis around the frontal horns of the lateral ventricles correlated significantly with severity of leukoaraiosis of the centrum semiovale adjacent to the bodies of the lateral ventricles. Cerebral blood flow values for all representative cerebral regions except the parietal white matter were reduced among the patients compared with the normal volunteers. Multivariate regression analysis revealed that reduced cerebral perfusion in the putamen and thalamus correlated significantly with the severity of leukoaraiosis. Cerebral hypoperfusion in territories supplied by deep penetrating arteries may contribute to the pathogenesis of leukoaraiosis.