Multi-infarct dementia

Fifty-two patients presenting with dementia were divided into a group in whom clinical features suggested an ischaemic basis (multi-infarct dementia) and a group in whom a primary degenerative process seemed more likely. Focal EEG changes and angiographic evidence of ischeamic areas and atheromatous disease of intracranial vessels were more common in the “ischaemic” than in the primary degenerative group. CBF was significantly reduced in the former but the regional pattern was equally distorted in the two groups. These findings strengthen the belief that the ischaemic score can identify those patients whose dementia is associated with vascular disease.     

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 Alzheimer's 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.     

Cerebral blood flow in severity-matched Alzheimer and multi-infarct patients

Cerebral blood flow was studied in patients meeting research criteria for either Alzheimer's disease or multi-infarct dementia, matched for age and severity of dementia. In both groups, mean flow was less than in age-matched normal controls, but the Alzheimer patients also had significantly lower mean flow than the multi-infarct group. This result helps resolve discrepancies found in studies with inadequate control for severity. Either global flow or regional left parietal flow could be used to discriminate between these dementia categories with 87% accuracy.     

Cognition and cerebral blood flow fluctuate together in multi-infarct dementia

Longitudinal measurements of cognitive ability measured by serial testing using the Cognitive Capacity Screening Examination (CCSE) were correlated with cerebral blood flow (CBF) throughout (mean +/- SD) 19.9 +/- 12.6 months among 57 patients with multi-infarct dementia, 17 with dementia of the Alzheimer's type, 10 with both, and among 32 age-matched elderly normal controls. Longitudinal CCSE and CBF measurements among controls yielded stable normative values. Reduced mean CCSE scores correlated directly with CBF reductions in patients with multi-infarct dementia (p less than 0.0005) and dementia of the Alzheimer's type (p less than 0.028). Patients with multi-infarct dementia had CCSE scores with retest variability exceeding those of controls (p less than 0.001) and of patients with dementia of the Alzheimer's type (p less than 0.003). CCSE scores and CBF changed together 78.6% (p less than 0.001) of the time in patients with multi-infarct dementia compared with 66.2% of the time (p less than 0.01) in those with both, 62.9% of the time (p less than 0.05) in those with dementia of the Alzheimer's type, and 47.7% of the time (NS) in controls. Further analyses indicated that changes in CCSE scores and CBF were predominantly progressive declines in patients with dementia of the Alzheimer's type, whereas the changes were more bidirectional (both increases and decreases) in patients with multi-infarct dementia; these differences were also significant. Results support the diagnostic usefulness of the Hachinski ischemic scale and confirm that both cognition and CBF fluctuate together among patients with multi-infarct dementia, whereas patients with dementia of the Alzheimer's type exhibit a more stable course, with progressive declines in cognition and CBF.     

Prospective analysis of long term control of mild hypertension on cerebral blood flow

A group of 12 otherwise normal elderly volunteers (mean age = 69.8 years), were detected to have mild hypertension. Cerebral blood flow (CBF) values were measured using 133Xe inhalation method prior to initiating medical treatment and repeated at 6, 12, 24 and 36 months after BP was adequately controlled and restored to normal (below 150/90). Results indicate that CBF values increased markedly during follow-up intervals at 6, 12 and 24 months but not at 36 months. Hypertension is known to be a risk factor for stroke and 4 of the 12 subjects subsequently developed symptoms of cerebrovascular disease (stroke, multi-infarct dementia or transient ischemic attacks) despite control of hypertension. Analyses separating asymptomatic and symptomatic groups indicated that the eight asymptomatic patients continued to maintain increased CBF levels throughout the entire three year interval, whereas the 4 symptomatic patients developed declines in CBF which began, and progressively decreased below the initial pretreatment values, during the second and third years.     

Glycosaminoglycan polysulfate in old-age dementias: a factor-analytic study of change in psychopathologic symptoms

In a multicenter clinical trial, two dosages of glycosaminoglycan polysulfate were compared in patients with primary degenerative dementia and multi-infarct dementia. Psychopathologic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). A factor analysis of this scale revealed four factors in this population. During the clinical trial, significant improvements were noted on the primary BPRS factor (i.e. depressive withdrawal), as well as on total BPRS score. There was a tendency for greater improvement in the primary degenerative dementia group than in the multi-infarct dementia group.     

Effects of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood.

Cerebral blood flow (CBF) and mean arterial pressure (MAP) were monitored in six normal baboons and six further animals in which an artificial subarachnoid haemorrhage (SAH) had been induced one week previously. MAP was reduced by the infusion of sodium nitroprusside. In the normal animals with administration of sodium nitroprusside, CBF increased initially but started to decrease as MAP was reduced below 65 mm Hg and fell below its baseline value when MAP was less than 50 mm Hg. In the SAH group, there was no initial hyperaemic response and CBF fell below baseline values when MAP was reduced below 50 mm Hg. When, during the infusion of the sodium nitroprusside, MAP was returned to normal using angiotensin, CBF increased above its baseline value. These results suggest that the cerebrovascular effects of sodium nitroprusside are the net result of competition between direct cerebral vasodilatation, falling arterial blood pressure and the degree of impairment of the "autoregulatory" mechanism. Evidence of ischaemic brain damage was found in the arterial boundary zones of both groups of animals.     

The value of transcranial Doppler sonography in the differential diagnosis of Alzheimer disease vs multi-infarct dementia

Primary degenerative dementia of the Alzheimer type and multi-infarct dementia exhibit differences in cerebrovascular blood flow velocity profiles, which were investigated by means of transcranial Doppler sonography. The pulsatility indices, as angle-independent parameters of peripheral vascular resistance, measured in middle cerebral and basilar arteries of patients with multi-infarct dementia (MID), were significantly increased (p<0.005) with respect to cases of primary degenerative dementia of the Alzheimer type and to healthy age-matched controls. Approximately 75% of all MID patients exhibited small vessel disease rather than thromboembolism from the extracranial arteries and the heart, as judged by extracranial and transcranial Doppler sonographies, computerized cerebral tomographies, EEGs, and, if necessary, 2-D echocardiographies.     

Prospective neuropathological validation of Hachinski''s Ischaemic Score in dementias.

The sensitivity and specificity of Hachinski's Ischaemic Score (IS) in the diagnosis of the vascular aetiology of dementia was studied in a series of 32 demented patients, dementia of the Alzheimer type (16), multi-infarct dementia (7), mixed dementia (6), Pick's disease (3), with neuropathological diagnosis as the point of reference. The IS distinguished between primary degenerative dementia and multi-infarct or mixed dementia. As single features of the IS "a positive history of stroke" and "a fluctuating course" showed differing prevalences in the latter two diagnostic categories. The IS labelled 21% of patients with primary degenerative dementia as having a vascular aetiology. The uncritical application of the IS to large samples in epidemiological studies may cause incorrect labelling of a significant proportion of patients with primary degenerative dementia as vascular dementia. These results are based on observations of long-term inpatients and depend on neuropathological criteria. While the definite diagnosis of DAT by threshold criteria concerning plaque and tangle counts is well established, neither clinical nor pathological evidence of stroke necessarily means that cerebrovascular disease has anything to do with a patient's dementia.     

Short-latency somatosensory evoked potentials in degenerative and vascular dementia.

Short-latency somatosensory evoked potentials (SEPs) were recorded from 54 patients with dementia as compared to 32 age-matched controls. SEPs were generally normal in patients with senile dementia of Alzheimer type, while patients with multi-infarct dementia showed a prolonged central conduction time, an increased latency of both N13 and N20 and a reduction of the primary cortical response amplitude. These findings suggest that recording SEPs may be useful in the differential diagnosis between degenerative dementia and multi-infarct dementia.     

Effect of tinofedrine (Homburg D8955) on cerebral blood flow in multi-infarct dementia.

Tinofedrine, a new derivative of l-norephedrine, was examined for cerebral vasodilator activity in man. Ten patients with reduced cerebral blood flow (CBF) and multi-infarct dementia were given the drug intravenously. Cerebral blood flow increased significantly by 28% from a mean of 43.3 to 55.5 ml/100 g/min.     

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.     

Positron emission tomography study of the human hypothalamus during normal ageing and in ischemic and degenerative disorders.

Regional blood flow and oxygen metabolism were determined by positron emission tomography, using the steady state technique with 15O, in the hypothalamus and in the whole brain of fifty two normal persons and patients suffering from cerebral ischemia and degenerative dementia. During normal ageing regional blood flow and oxygen consumption appeared to increase slightly in the hypothalamus and to decrease in the whole brain in 24 persons. In the young age group the hypothalamus was more protected against ischemia than in the elderly group. In the aged group with cerebral ischemia and degenerative dementia regional blood flow and oxygen consumption were decreased in the hypothalamus to the same extent as in the whole brain.     

Progression of illness in the differential diagnosis of primary dementia

The diagnostic utility of determinations of insidious or stepwise progression of illness was examined in 124 geriatric inpatients with primary dementia. Such determinations failed to distinguish patients with primary degenerative dementia of the Alzheimer type from those with multi-infarct dementia. Episodic behavioral complications, especially depression and delusions, in the patients with primary degenerative dementia were associated with stepwise progression. Determinations of stepwise progression were made in only six (15%) of the 40 demented patients with at least two cerebral infarctions, a finding inconsistent with current diagnostic criteria for multi-infarct dementia.     

Abnormal cerebrospinal fluid-blood flow dynamics. Implications in diagnosis, treatment, and prognosis in normal pressure hydrocephalus.

Increased cerebral blood flow (CBF) has been proposed as responsible for the clinical improvement after cerebrospinal fluid (CSF) shunting in patients with normal pressure hydrocephalus (NPH). In order to determine any abnormal CSF-CBF pressure-flow relationships in NPH, measurements of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were made before and after lowering CSF pressure (CSFP) in 15 patients with NPH, and in ten patients with presumed hydrocephalus ex vacuo. Maximal reduction of rCBF and rCBV occurred in the territory of the anterior cerebral artery in NPH but no in dementia due to brain atrophy. Both CBF and rCBV increased after lowering the CSFP by lumbar puncture in patients with NPH. Patients with higher preoperative rCBF and maximal increases in rCBR and rCBV after lowering CSFP showed the most consistent clinical improvement after CSF shunting. Evidence is offered that CBF autoregulation is impaired in NPH. The CBF test assists in both diagnosis and selection of patients for CSF shunting.     

Cerebral blood flow and metabolism in multi-infarct dementia

Cerebral blood flow and oxygen metabolism were studied in three aged normal volunteers and 10 patients with multi-infarct dementia (MID) by Positron Emission Tomography using O-15. The diagnosis of MID was done according to the Loeb's modified ischemic score and X-ray CT findings. The MID patients, whose X-ray CT showed localized low density areas in the subcortical white matter and basal ganglia and thalamus, were studied. No occlusion was observed at anterior cerebral artery and/or middle cerebral artery on cerebral angiography. All cases of MID were mild dementias. Regional CBF, rOEF and rCMRO2 were measured by the steady state technique described by Terry Jones et al. The values of rCBF in MID patients were significantly low compared with those of aged normal subjects in frontal, temporal, occipital, parietal cortices and thalamus. The values of CMRO2 in MID were significantly low in frontal, temporal, occipital cortices and thalamus compared with normal subjects'. The OEF was 0.46 in aged normal subjects, and 0.52 in MID patients. The MID patients in the early stage of dementia showed the increased oxygen extraction fraction, and this fact suggests that ischemia is a significant pathogenic mechanism in the production and progression of multi-infarct dementia. The decrease of CBF and CMRO2 in MID compared from normal subjects' were most remarkable in frontal cortex. The impairment of mental functions in MID should be caused by the decreased neuronal activities in frontal association cortex.     

Modern concepts of "cerebrovascular dementia"

The incidence of both atherosclerosis and demential increases with age and therefore the terms "cerebral atherosclerosis" or "cerebro-vascular dementia" are commonly used for any mental deterioration in elderly persons. These names depend on the proposition of a gradual narrowing of cerebral arteries as an inevitable accompaniement of ageing which ends in dementia through a progressive reduction of cerebral blood flow. This apparently reasonnable hypothesis has now been shown to be wrong. ;t has been established that first, senile dementia is not due to cerebral atherosclerosis in spite of the frequent coexistence of degenerative and vascular lesions; and secondly, true cerebro vascular dementia results from the destruction of brain tissue following cerebral infarction; hence the proper term is "multi-infarct dementia". This neuronal destruction leads to decrease in cerebral metabolism and blood flow and to intellectual deterioration. The diagnostic criteria are therefore those of cerebral infarcts i.e: arterial hypertension and/or signs of atherosclerosis, sudden onset and/or stepwise progression, and focal neurological signs. If one follow those criteria, multi-infarct dementia accounts for only about 10% of all dementias; if one does not, the diagnosis will continue to be made to the exclusion of other potentially curable causes of dementias. Five clinico-pathological forms can be distinguished according to the size, number and site of the infarcts: lacunar state, large multiple infarcts, watershed infarction, single infarct and Binswanger's encephalopathy. This distinction is always arbitrary because the association of lacunes and large infarcts is very common in multi-infarct dementia. The almost invariable failure of all therapeutic measures once multi-infarct dementia has been established stresses the importance of prevention. This depends on prevention of cerebral infarcts, i.e. on the correction of risk factors amongst which arterial hypertension is by far, the most important. Some cases benefit also from carotid surgery, anticoagulants, and antiplatelet drugs but antihypertensive drugs are the most essential part. It is very likely that if all cases of arterial hypertension are properly treated, the incidence of multi-infarct dementia will decrease greatly.     

Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.     

Cerebral blood flow and cognitive testing correlate in Huntington's disease

Brain atrophy estimated by computed tomographic (CT) scanning and mean hemispheric and regional gray matter cerebral blood flow (CBF) values were measured in patients with mild to moderate Huntington's disease (HD) (N = 16) using the xenon Xe 133 inhalation method and in asymptomatic blood relatives at risk from HD (N = 6) using both the xenon Xe 133 inhalation and the stable xenon CT contrast CBF methods. Results were compared with measurements in two groups of age-matched normal volunteers (N = 48 and N = 42, respectively). Significant brain atrophy in the vicinity of both caudate nuclei was present in patients with HD but not in at-risk individuals. Mean hemispheric xenon Xe 133 CBF values were reduced in patients with HD but seemed to be normal in at-risk individuals. In HD, reductions in CBF were found in both frontotemporal regions. Correlations were found between severity of dementia estimated by reductions of Mini-Mental Status Questionnaire scores and reductions of either mean hemispheric or regional frontotemporal CBF values in HD. The CT estimates of brain atrophy and three-dimensional CBF by stable xenon-contrast measurements were normal in asymptomatic individuals at risk from HD.     

Neurological complications of vasculitis

Raw scores for cerebral blood flow (CBF), determined by xenon 133 inhalation, and for Wechsler Adult Intelligence Scale (WAIS) were measured in five groups of 12 subjects each: young normals, aged normals, and patients with cerebrovascular disease without dementia, dementia with cerebrovascular disease, and degenerative brain disease. Important differences were present in the raw data according to age and sex. When these were adjusted a quadratic model revealed a highly significant (p < 0.0001, r = 0.86) correlation between CBF and measured intelligence score. We interpret these findings to indicate that in dementing illnesses the WAIS raw score reflects the severity of the brain disorder, regardless of cause, and that CBF is reduced as a function of the severity rather than the cause of the abnormality.