Karl F. Mortel

Cerebral blood flow changes in benign aging and cerebrovascular disease

Cross-sectional analysis of CBF values was carried out among 668 volunteers and patients. Subjects were subdivided according to age, gender, and degree of cerebrovascular disease, ranging from healthy volunteers with or without risk factors for stroke to patients with multi-infarct dementia. Four-year longitudinal analysis was also carried out on 230 individuals from the original sample, Decrements in CBF values were evidenced by both cross-sectional and longitudinal analysis in relation to advancing age, progressive cerebrovascular disease, and dementia. Regional, age-related CBF declines in healthy volunteers were heterogeneous, possibly related to changes in levels of functional activity within different brain regions.

Decreased cerebral blood flow precedes multi‐infarct dementia, but follows senile dementia of Alzheimer type

A 7-year prospective study among 181 neurologically normal elderly volunteers (mean age, 70.6 years) revealed an incidence of 3.3%, or 0.47% new cases per year, for Alzheimers disease (SDAT) and 5.5%, or 0.78% new cases per year, for multi-infarct dementia (MID). The unusually high incidence of MID is considered to reflect preselection of a large percentage of volunteers (48.6%) with risk factors for (but without symptoms of) atherothrombotic stroke. Of 88 volunteers at risk of stroke, 11.4% developed MID within 7 years. In MID patients, cerebral blood flow (CBF) values began to decline around 2 years before onset of symptoms, while in SDAT patients, CBF levels remained normal until symptoms of dementia appeared; thereafter, CBF declined rapidly.

Education and Occupation as Risk Factors for Dementias of the Alzheimer and Ischemic Vascular Types

Education and occupation as sociodemographic risk factors for dementias of the Alzheimer (DAT) and ischemic vascular types (IVD) were evaluated by two case series studies. Cases were compared to well-evaluated individuals identified as healthy normals acting as controls. There were 150 patients with probable DAT, 102 patients with probable IVD, and 188 neurologically and cognitively normal subjects. Logistic regression indicated that for DAT, education with occupation was the best predictor (OR, 1.51; 95% CI, 1.23-1.87). For IVD, the two predictors were: education with occupation (OR, 1.84; 95% CI 1.38-4.50) and education with gender (OR, 3.40; 95% CI, 1.29-8.92). We conclude that risk of dementia is increased in those with limited educational background and occupational achievement.

Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

Classification, Diagnosis and Treatment of Vascular Dementia

SummaryVascular dementia (VAD) is considered to be the second most common cause of dementia in Europe and the US. In Asia and many developing countries, it is more common than dementia of the Alzheimer’s type (DAT). VAD is the most preventable form of dementia associated with later life. The pathogenesis of VAD is multifactorial, and it represents a heterogeneous, not a homogeneous, clinical entity. Classification of VAD by pathogenesis is important for its prevention and treatment. Control of the risk factors for VAD reduces its incidence and stabilises or improves cognitive performance following stroke.Proper diagnostic evaluation of VAD requires: (i) a well defined quantitative assessment of the cognitive deficits present; (ii) assessment of risk factors for stroke; (iii) identification of cerebral vascular lesions by history, neurological examination and neuroimaging; (iv) exclusion of other causes of dementia;(?) establishment of a positive diagnosis of possible, probable or definite VAD versus DAT or mixed VAD/DAT; and (vi) identification of the temporal relationship between cognitive deficits and cerebral vascular lesions.VAD can be subdivided into 8 major types, as follows: (i) multi-infarct dementia secondary to large cerebral emboli [type 1]; (ii) strategically placed infarctions causing dementia [type 2]; (iii) multiple subcortical lacunar lesions secondary to atherosclerosis or degenerative arteriolar changes [type 3]; (iv) Binswanger’s disease (arteriosclerotic subcortical leukoencephalopathy) [type 4]; (v) mixtures of types 1, 2 and 3 [type 5]; (vi) haemorrhagic lesions causing dementia [type 6]; (vii) subcortical dementia secondary to hereditary factors (type 7); and (viii) mixtures of DAT and VAD (type 8). Treatment is dictated by the pathogenetic subtype of VAD that is present.

Stable xenon CT cerebral blood flow measurements computed by a single compartment--double integration model in normal aging and dementia.

Programs have been developed, using a single compartmental analysis model, that provide rapid computer derivation for values of both local cerebral blood flows (LCBF) and local tissuc:blood partition coefficients (LA) using inhaled stable xenon gas (Xes) as the indicator. These programs are planned for utilization of raw data points derived from serial computed tomography scans made between the 3rd and 9th min after 35% Xes inhalation, while concentrations of end-tidal Xes (PEXes) are concurrently monitored. Double integration and least squares fitting permitted estimation of corresponding arterial (assumed from PEXes) and tissue Xes concentrations at each scanning interval during Xes saturation. Derived estimates for LA and LCBF values for each region of interest mathematically approximate values saturated to infinity. The method described can be utilized for any freely diffusible indicator. Cross-sectional analysis of results obtained in 13 normal healthy volunteers between 20 and 80 years of age showed no age-related changes in LA values but progressive decreases in blood flow of cortex, basal ganglia, and white matter with advancing age. In senile dementia of Alzheimers type (SDAT. n=8) LA values were likewise found to be unchanged, but cortical and thalamic gray matter LCBF values were significantly reduced compared to age-matched normal volunteers.

Effects of Estrogen Replacement Therapy on Cerebral Perfusion and Cognition among Postmenopausal Women

Previous investigations concerned with effects of estrogen replacement therapy (ERT) in older women have focused primarily on morbidity and mortality as measures of outcome. A retrospective study is r

Age-Related Reductions in Cerebral Vasomotor Reactivity and the Law of Initial Value: A 4-Year Prospective Longitudinal Study

A group of 51 neurologically normal, middle-aged and elderly volunteers (aged 35–86 years; mean age 63.24 years) with and without risk factors for stroke were given annual tests of cerebral vasomotor reactivity to assess any changes in the cerebral vascular capacitance associated with advancing age that might alter cerebral vasomotor reactivity. Cerebral vasomotor reactivity was estimated as the difference in bihemisphere gray matter CBF measured by the 133Xe inhalation method in the steady state breathing room air, followed by a second measurement during inhalation of 100% oxygen. There were significant and progressive reductions in cerebral vasomotor reactivity during the 4-year longitudinal study. Positive linear correlations were apparent between initial steady-state mean bihemisphere gray matter CBF levels and degrees of vasomotor reactivity, suggesting that the Law of Initial Value plays an important role. This should be borne in mind when analyzing scores of cerebral vasomotor reactivity. In the present communication, analysis of covariance was used to correct for influences of initial CBF levels on vasomotor responses tested while breathing pure oxygen.

Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type.

Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are +9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus -2.5 ml, total white matter -0.6 ml, frontal white matter -0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007).

Patterns of cerebral hypoperfusion compared among demented and nondemented patients with stroke.

Background and Purpose No reports are available that compare local cerebral perfusion among groups of patients suffering from multiple cerebral infarctions with and without cognitive impairments. The present study was designed to correlate changes in regional cerebral perfusion that may lead to dementia among patients with multiple cerebral infarctions by comparing measurements of local cerebral blood flow. Methods Local perfusion was measured using xenon-contrasted computed tomographic scanning among two groups of patients who had suffered from multiple cerebral infarctions: Group D (n=12) were demented and had severe cognitive impairments, and group I (n11) were cognitively intact Results were compared with similar measurements among neurologically and cognitively normal, age-matched volunteers (group N, n=16). Results Mean local perfusion values were reduced among both groups with cerebral infarctions but to a more marked degree in group D (p<0.05). Perfusion of cerebral white matter was diffusely and severely reduced in group D (p<0.05) but was mildly reduced only in frontal and capsular white matter in group I (p<0.05). Perfusion of cerebral cortex was reduced in frontal (p<0.01) and temporal (p<0.01) regions among both groups but to a significantly greater degree in group D subjects (frontal, p<0.05; temporal, p<0.01), who also showed hypoperfiision of the occipital cortex (p<0.05), apparently because of underlying leukoaraiosis and cortical disconnections. Perfusion of the basal ganglia was reduced to the same degree among both groups of stroke patients (p<0.01). Conclusions: Leukoaraiosis with white matter hypoperfusion appears to be an important determinant for cognitive impairments among patients with multiple cerebral infarctions.