Transcranial Doppler sonography as a diagnostic tool in vascular dementia

Transcranial Doppler monitoring of the flow velocity at the level of the middle cerebral artery was performed in 40 demented patients, 20 with multi-infarct dementia (MID) and 20 with senile dementia of the Alzheimer type (SDAT), and in 25 age-matched controls. The following conditions were evaluated: (1) rest; (2) 60 s hyperventilation; (3) longest possible apnea, and (4) 5 min closed-circuit air rebreathing. We also measured: PaCO2 levels at rest and under stimulus conditions; mean flow velocity and pulsatility index (PI) at rest, and percentage velocity variations. The PIs were higher and the velocity decrease during hyperventilation was lower in all demented patients than in the healthy group; no side-related asymmetry in rest values or in vasomotor responses to CO2 changes was regularly detected in any group. On the contrary, rest flow velocities and vasomotor responses to hypercapnia induced by both apnea and rebreathing tests proved to be lower in MID patients than in SDAT and healthy groups. These alterations were neither exclusive to MID patients nor homogeneous, therefore some caution should be taken when evaluating single cases.     

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 hypoperfusion correlates with mild and parenchymal loss with severe multi-infarct dementia.

Relative contributions of two potential pathogenetic factors for cognitive impairments among patients with multi-infarct dementia (MID) are reported. Cognitive test scores were correlated with measures of cerebral hypoperfusion and loss of brain parenchyma. Local cerebral blood flow values were determined utilizing stable xenon contrasted computed tomography and volumes for brain parenchyma were estimated from ratios of volumes of infarcted brain plus cerebrospinal fluid/total intracranial volume measured on the same CT slices among two groups of patients, one with mild and the other with severe MID. A total of 26 demented patients with multiple cerebral infarcts were divided into 2 index groups, one with mild and the other with severe MID (mild MID, CCSE greater than or equal to 15, n = 16; severe MID, CCSE less than 15, n = 10). Results were compared with similar measures among age-matched neurologically normal volunteers (n = 14). Ratios for volumes of lost brain parenchyma were significantly higher among severe MID patients than among age-matched normal volunteers, whereas estimates of brain loss among patients with mild MID did not differ from elderly normal volunteers. In patients with mild MID, LCBF values for cortical gray matter were decreased compared with age-matched normal volunteers. Results suggest that chronic cerebral hypoperfusion is an important determinant for mild dementia among patients in the early stages of MID, but volumes of lost cerebral parenchyma due to cerebral infarctions is an important determinant for advanced stages of MID.     

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.     

Autonomic nervous functions in Alzheimer type and multi-infarct dementia--a hemodynamic study

As it has been recently postulated that patients with dementia have some altered neural transmission, these patients are speculated to accompany autonomic dysfunctions. The present study was aimed at investigating autonomic nervous functions in dementia of Alzheimer type (DAT) and multi-infarct dementia (MID). Hemodynamic autonomic functional tests were carried out on 14 patients with DAT (66.9 +/- 11.4 YO; mean +/- SD) and 9 patients with MID (73.1 +/- 7.5) and 16 age-matched healthy volunteers as controls. Blood pressure, pulse rate and respiration were continuously measured. The degree of reflex bradycardia in Aschner's test, a parameter for parasympathetic functions, was significantly lower in MID than in DAT and in the healthy volunteers (p less than 0.01, p less than 0.05, respectively), but there was no significant difference between DAT and the healthy volunteers in this reaction. The degree of reflex hypertension in cold pressor test, a parameter for sympathetic functions, was not significantly different among 3 groups. The degree of orthostatic hypotension also failed to show any significant difference among the groups. From the above data, it is suggested that the patients with DAT have preserved autonomic nervous functions, but that the patients with MID have impaired parasympathetic and normal sympathetic nervous functions.     

Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of alzheimer type and multi-infarct dementia

Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group.

MID patients had significantly (P < 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P < 0.01) and AD/SDAT (P < 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P < 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P < 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios.

There were no signs of local synthesis of IgG in CNS in either group of demented patients.     

Plasma cholinesterase activities in dementias,depressions and schizophrenia

Plasma cholinesterase activities were measured in a group of elderly patients and controls. Total cholinesterase activity was found to be decreased to a just significant extent in those suffering from endogenous depression when compared to normal controls. There was a highly significant decrease in cholinesterase activity in the plasma of patients suffering from senile dementia of Alzheimer type (SDAT) but not in those suffering from multi-infarct dementia, neurotic depression or chronic schizophrenia. There was a just significant correlation between total cholinesterase and acetylcholinesterase activity in the plasma of patients suffering from SDAT and the degree of dementia. There were also significant differences between patients with SDAT and MID, and patients with endogenous and reactive depression. The potential use of such tests is discussed.     

Prolactin responses to thyrotropin-releasing hormone in multi-infarct dementia and senile dementia of the Alzheimer type

The serum prolactin (PRL) responses to stimulation with thyrotropin-releasing hormone (TRH) (500 micrograms Protirelin) were compared in 14 patients with multi-infarct dementia (MID) and 10 patients with senile dementia of the Alzheimer type (SDAT). Between the MID and the SDAT patients, there were no statistically significant differences in the median serum PRL concentrations, median changes in serum PRL concentrations or median proportional changes in serum PRL concentrations. Further, the serum PRL responses did not correlate with the GBS scale scores (degrees of dementia) or the GBS subscale scores (clinical profiles, including motor functioning, emotional functioning and intellectual functioning). In conclusion, the study does not support the hypothesis that serum PRL responses to TRH stimulation are of diagnostic value in differentiating between MID and SDAT.     

Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis

Summary Autopsied brains from 55 patients with dementia between 59–95 years of age (mean age 77.9±8.1 years) and 19 non-demented individuals between 46–91 years of age (mean age 74.3±10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimer's disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in the AD-MID patients was not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process.     

Correlations between EEG and CT in 79 cases of dementia

An EEG and CT study was carried out on 79 patients affected by dementia (24 SDAT and 55 MID). The EEG and CT patterns were compared with those of an age-matched control group. Statistical analysis of the CT findings between the demented and normal subjects showed significant differences only for severe atrophy. As far as EEG findings are concerned, no EEG pattern indicative of a specific type of dementia was observed even though a greater number of abnormal EEGs occurred in demented patients than in the control group. Finally, a poor EEG-CT correlation was found in demented patients.     

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).     

Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients.

CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.     

Predictors of survival in clinically diagnosed Alzheimer's disease and multi-infarct dementia

Duration of survival from time of first evaluation was studied in 61 patients with clinically diagnosed Alzheimer's disease (senile dementia of the Alzheimer type [SDAT]) and 34 patients with clinically diagnosed multi-infarct dementia (MID). Duration of survival did not differ significantly between MID and SDAT. However, since MID patients were younger at onset, MID patients had a lower life quotient than SDAT patients. Race, sex, and age at onset were not predictive of survival in SDAT. History of hypertension, elevated systolic blood pressure, lower scores on tests of Block Designs, and Logico-Grammatical Comprehension predicted shorter survival in SDAT. Age at onset and race were not predictive of survival in MID. Male sex, lower educational attainment, as well as low scores on tests of Logico-Grammatical Comprehension, Digit Span, Naming, Verbal Fluency, and receptive vocabulary, predicted shorter survival in MID.     

The effect of neuroleptic treatment and of high dosage diazepam therapy onβ-endorphin immunoreactivity in plasma of schizophrenic patients

Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.     

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.     

The Comprehensive Psychopathological Rating Scale in patients with dementia of Alzheimer type and multiinfarct dementia

ABSTRACT– Eighteen patients with the clinical diagnosis dementia of Alzheimer type (AD/SDAT) and 20 patients with the clinical diagnosis multiinfarct dementia (MID) were interviewed using a subscale to the Comprehensive Psychopathological Rating Scale (CPRS), consisting of items measuring psychopathological symptoms and signs commonly seen in patients with dementia. The aim of the investigation was to evaluate whether a difference in psychopathology between AD/SDAT and MID could be observed during a semistructured psychiatric interview using the CPRS. In both groups the duration of illness was similar and the dementia mild to moderate. All patients were subjected to somatic, psychiatric, laboratory, neurophysiologic and neuroradiologic examinations in order to obtain the correct clinical diagnoses. The results show that patients with AD/SDAT have a more variable psychopathology than patients with MID. Patients with MID were rated lower on all items used, especially those concerning verbal and personal contact. This might explain the generally accepted opinion that patients with MID have better contact with their surroundings and better preservation of their personality, even though they have the same degree of dementia as patients with AD/SDAT.     

Regional cerebral blood flow in Down's syndrome

Regional cerebral blood flow was measured in 14 patients with Down's syndrome, in 46 patients with Alzheimer's disease and senile dementia of the Alzheimer type, and in 114 age-matched controls, using the xenon 133 inhalation technique. Cerebral blood flow was reduced in 13 of 14 Down's patients by a mean of 16.8 +/- 2.5% from expected age-matched normal values. Degrees of regional cerebral blood flow reduction did not differ among the frontal, temporal, parietal, and occipital regions in both cerebral hemispheres. The regional cerebral blood flow decreases were similar in magnitude and pattern to those in Alzheimer patients. These findings constitute an additional similarity between the two disorders.     

Regional cerebral blood flow in normal pressure hydrocephalus.

Regional cerebral blood flow (rcbf) was studied preoperatively and at 2 and 6 months postoperatively in 22 normal pressure hydrocephalus patients using xenon-133 inhalation and single photon emission computed tomography. Sixteen of the 22 patients improved (improved group) and six did not (unimproved group). The following comparisons were made: (1) preoperative rcbf in the improved group, to 14 normal elderly volunteers and to that in 59 SDAT (senile dementia of the Alzheimer type) patients; (2) preoperative rcbf in the improved and unimproved groups to determine if rcbf could predict surgical outcome; (3) pre- to postoperative rcbf in the improved group to see if increased cbf accounted for clinical improvement. The findings were: (1) preoperative rcbf in the improved group was lower than that in normal controls but was the same as that in SDAT; however, the ratios of rcbf values in anterior and posterior brain regions were significantly different between improved group and SDAT (p = 0.02); (2) an anterior/posterior ratio of 1.05 correctly classified surgical outcome in 19/22 patients; five of six in the unimproved group were above this cut off while 14/16 in the improved group were below; (3) in the improved group rcbf increased at 2 but not at 6 months after surgery without a corresponding reduction of clinical signs, supporting the notion that increase in cbf probably does not account for clinical improvement in normal pressure hydrocephalus.     

Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of the Alzheimer type

Cholinesterase (ChE) activity and somatostatin-like immunoreactivity (SLI) of the cerebrospinal fluid were determined for 59 patients with dementia of the Alzheimer type (AD/SDAT) and for 19 age-matched control patients with no signs of dementia. Both ChE activities and SLI concentrations of cerebrospinal fluid were reduced significantly in dementia patients compared to the controls. In the AD/SDAT patients cholinesterase and somatostatin-like immunoreactivity levels seemed to be correlated with the severity of dementia. These findings agree with observations of reduced cortical acetylcholinesterase activities and somatostatin values in dementia of the Alzheimer type.     

Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer's disease.

BACKGROUND: Recently it has been reported that activation of the inflammatory response system (IRS) may play a role in the aging process and in the pathogenesis of the degenerative changes associated with Alzheimer's disease (SDAT). The aims of the present study were to examine the peripheral IRS in normal aging and in SDAT patients. METHODS: Serum zinc (Zn), total serum protein (TSP), albumin (Alb), SP electrophoresis, and serum interleukin-6 (IL-6) and the stimulated production of tumor necrosis factor-alpha (TNFalpha) were determined in younger versus elderly healthy subjects and in SDAT patients vs. age-matched, healthy volunteers. RESULTS: Serum Zn and Alb were significantly lower in elderly than in younger healthy volunteers and were significantly and inversely correlated with age. The production of TNFalpha was significantly higher in elderly than in younger healthy volunteers and was significantly and positively correlated with age. In SDAT patients, no significant changes in serum Zn or TNFalpha production could be found. Serum Alb was significantly lower and serum IL-6 and the alpha1 and alpha2 globulin fractions significantly higher in SDAT patients than in controls. CONCLUSIONS: Activation of the IRS appears to accompany the normal aging process, i.e. lower serum Zn and Alb and increased TNFalpha production, as well as SDAT, i.e. lower serum Alb and increased serum IL-6 and alpha1 and alpha2 globulin fractions. The findings suggest that not all indicators of IRS activation in SDAT are related to those of the normal ageing process.