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).     

Cerebral perfusion patterns in vascular dementia of Binswanger type compared with senile dementia of Alzheimer type: a SPECT study

Summary Cerebral perfusion patterns in 18 cases with vascular dementia of Binswanger type (VDBT) (8 moderate and 10 severe cases) were compared with 25 cases with senile dementia of Alzheimer type (SDAT) (16 moderate and 9 severe cases) and 14 controls by single photon emission computed tomography usingN-isopropyl-p-¹²³I iodoamphetamine (IMP) as a tracer. The cerebral: cerebellar IMP uptake ratio (%) (CCR) was used as a measure of relative cerebral perfusion. The CCRs were about 85–90% in all areas in controls. Moderate VDBT patients showed a remarkable decrease of CCRs in the basal grey region (thalamus and basal ganglia) (right 79%, left 77%) and in the frontal area (right 79%, left 80%) (P<0.01). In severe VDBT patients a significant decrease of the CCR was noted in all regions (P<0.01). The decrease of mean CCRs in the hemispheres was significantly correlated with the severity of disease determined by psychometric testing. Patients with SDAT showed a significant decrease of the CCR in the parietal (right 71%, left 74%) and right temporal (78%) areas in the moderate stage (P<0.01), and further progression of dementia was associated with low perfusion areas extending to the frontal areas (78%,P<0.01). These differences in the perfusion patterns and their changes with progression of the illnesses may be reflected in characteristic clinical features.     

Cerebral dysfunction in alcoholism and presenile dementia

Fifteen chronic alcoholics and 15 presenile patients were matched in pairs with regard to their mean hemisphere cerebral blood parameters - an index of brain metabolism. The distribution of the regional cerebral blood flow was similar in the two groups. The alcoholics performed significantly better in all psychometric tests than the presenile patients and more alcoholics than presenile patients were still employed and working. Nine presenile patients and one alcoholic showed symptoms indicating brain stem dysfunction. The measurements of the cerebral blood flow were made at rest while the psychometric testings and the evaluation of the social performace gave information about the brain at work. It is suggested that cerebral dysfunction in alcoholics to some extent can be partly overcome by brain activation procedures. In contrast, the defects of higher mental functions in presenile dementia cannot be compensated for.     

Neuropsychiatric studies in a family with presenile dementia different from Alzheimer and Pick disease

ABSTRACT: We have studied a family in which 14 persons among 73 are or have been suffering from presenile dementia. Post mortem examination showed atrophy but no sign of any known demential syndrome. Cerebral blood flow measured in the late stage of disease was low, but with no characteristic pattern in flow distribution. In one patient in the initial stage of disease, the cerebral blood flow was unexpectedly increased. The patients with presenile dementia in this family did not reveal pathological signs of any known demential syndrom and showed CBF-changes not earlier reported. Moreover, contrary to widely held views we have evidence that dementia may be connected to a high blood flow at least in the initial state. An increased blood flow was also seen in seven of ten well functioning first degree relatives, in some cases along with cerebral atrophy and/or psychological tests with signs of dementia. Are these people going to develop manifest dementia later in life?     

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.     

Course characteristics in the differentiation of dementia of the Alzheimer type and multi-infarct dementia

Clinico-pathological studies have shown that the clinical diagnosis of multi-infarct dementia (MID) is even more difficult than that of dementia of the Alzheimer type (DAT). The study evaluated the significance of course characteristics for the diagnosis of MID and DAT. Course characteristics were rated when 57 demented patients were admitted to our neurogeriatric department. Diagnosis of MID and DAT, respectively, was established after a follow-up study with repeated neurological, psychiatric and neuropsychological investigations. In 21 cases diagnosis was confirmed by postmortem neuropathology. MID lacked the typical course of the disease in about two thirds of patients, while most DAT patients presented with the typical course of primary degenerative dementia. Features of the "typical" clinical course of MID (abrupt onset, stepwise deterioration) helped to exclude DAT, whereas MID could not be excluded on the basis of a history of insidious onset and gradual decline.     

Prevalence of moderate and severe Alzheimer dementia and multi-infarct dementia in the population of southeastern Sicily

We have calculate the prevalence rates of moderate and severe dementia of the Alzheimer type (DAT) and of multi-infarct dementia (MID) in a Sicilian population sample aged 40 and over. For DAT the prevalence rate is 0.80% among the over 40s and 2.42% among the over 65s. The prevalence rates for both types, but especially for DAT, increase higher prevalence of primary degenerative dementia among females.

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Sommario Abbiamo calcolato i tassi di prevalenza della demenza tipo Alzheimer e della demenza multiinfartuale di grado moderato e severo in un campione di popolazione siciliana di 40 anni ed oltre (4337 individui). Per la DAT il tasso di prevalenza è dello 0,80% [LF al 95% 0,56–1,11] nella popolazione di 40 anni ed oltre e diventa pari al 2,42% [LF al 95% 1,69–3,37] nella popolazione che ha raggiunto e superato il 65esimo anno di età.Per la MID la prevalenza è di 0,34% [LF al 95% 0,19–0,56] nella popolazione di 40 anni ed oltre, mentre nella popolazione di 65 anni ed oltre la prevalenza è dello 0,95% [LF al 95% 0,50–1,62].La prevalenza dei due tipi di demenza, e per quella tipo Alzheimer in particolare, aumenta significativamente con l'età. Altrettanto significativa è, sempre per la demenza degenerativa primaria, la più elevata prevalenza nel sesso femminile.

     

Nicotinic receptors in dementia of Alzheimer, Lewy body and vascular types

Objectives - Comparisons were made of nicotinic receptors in 3 major forms of dementia in old age. Although it is well established the involvement of nicotinic receptors in Alzheimer's disease (AD), their status in the other two main causes of dementia in old age – dementia with Lewy bodies (DLB) and vascular dementia (VaD) is not widely reported. Methods – Temporal cortex was examined for epibatidine and α-bungarotoxin binding, and immunoreactivity of α4 and α7 nAChR subunits. Results – There were selective abnormalities in nicotinic receptor subtypes in the disorders examined. In AD there is a loss of high affinity receptor binding, reflecting a selective loss of α4 subunit, but no change in α7 subunits. Similar abnormalities in ligand binding are also apparent in DLB. In the VaD series, there was no overall loss of epibatidine binding or immunoreactivity for α4 or α7 subunits. Conclusions – Loss of cortical receptor α4 subunit appears to be a characteristic feature of neurodegenerative dementia but not dementia of vascular origin. Since nicotinic receptors control cerebral vasodilation, the relative integrity of the receptors in VaD may auger well for nicotinic therapy in this disorder in which there is a cholinergic abnormality, to judge by the loss of the presynaptic enzyme.     

Delusions in Alzheimer's disease and multi-infarct dementia

Neuropsychiatric symptoms such as delusions and misidentifications have been reported in dementia ranging from 10% to 73% in Alzheimer's disease (AD) patients and up to 40% in multi-infarct dementia (MID) patients. The aim of this study was to investigate in 61 AD and 31 MID patients both the frequency and the content of delusions during the course of illness and to evaluate the relationship between these and both functional and mental decline. The results indicated that delusion experiences had occurred in 45% of AD patients and in 38% of MID patients, occurring most frequently during the first year of illness. Patients who experienced psychiatric symptoms showed higher mini mental state examination scores and were less impaired in functional disability measures. With regard to the content, no significant differences were observed between AD and MID patients; 53% of psychotic symptoms were found to be paranoid delusions while 47% were misidentification delusions.     

Cerebral blood volume changes during brain activation

Cerebral blood volume (CBV) changes significantly with brain activation, whether measured using positron emission tomography, functional magnetic resonance imaging (fMRI), or optical microscopy. If cerebral vessels are considered to be impermeable, the contents of the skull incompressible, and the skull itself inextensible, task- and hypercapnia-related changes of CBV could produce intolerable changes of intracranial pressure. Because it is becoming clear that CBV may be useful as a well-localized marker of neural activity changes, a resolution of this apparent paradox is needed. We have explored the idea that much of the change in CBV is facilitated by exchange of water between capillaries and surrounding tissue. To this end, we developed a novel hemodynamic boundary-value model and found approximate solutions using a numerical algorithm. We also constructed a macroscopic experimental model of a single capillary to provide biophysical insight. Both experiment and theory model capillary membranes as elastic and permeable. For a realistic change of input pressure, a relative pipe volume change of 21±5% was observed when using the experimental setup, compared with the value of approximately 17±1% when this quantity was calculated from the mathematical model. Volume, axial flow, and pressure changes are in the expected range.     

Cerebrospinal fluid investigations in multi-infarct dementia and senile dementia

Thirty-eight demented patients were clinically investigated and classified into a multi-infarct dementia (MID) and senile dementia (SD) group. Total protein, albumin, immunoglobulin G, agar gel electrophoretic protein and iso-electric focusing pattern were determined in CSF and serum as well as the lactate dehydrogenase, LD-iso-enzyme pattern and uric acid. No significant differences were found regarding total protein, albumin and immunoglobulin G. The agar gel electrophoresis showed a tau-globulin increase in 18% of the SD-group against 6% of the MID group. The patterns were, however, plasma-like in 56% of the MID group against 23% of the SD group. The iso-electric focusing pattern showed an abnormal band in some SD-patients which was not found in the MID group. The uric acid and LD-enzyme concentration was equal in both CSF and serum. An index was calculated to give an approximate correction for the influence of different permeability of the blood-brain and CSF barrier. A significantly higher LD-index was found in the SD-group, suggesting a continuous cell degeneration.     

Quantification of the heterogeneity of cerebral blood flow in vascular dementia

Background: In vascular dementia (VaD), assessment of cerebral blood flow by single photon emission computed tomography (CBF SPECT) has been used to detect a patchy decrease of blood flow or a frontal reduction. In addition to reduced blood flow, the heterogeneous distribution of cerebral blood flow is often observed in VaD. However, no objective method to evaluate the heterogeneity has been established. In this study, we applied three-dimensional fractal analysis (3D-FA) to CBF SPECT images as a method for assessing the heterogeneity of the cerebral blood flow distribution in VaD. Subjects and Methods: The subjects included 18 patients with a diagnosis of VaD (aged 69.7 ± 8.3) based on neuropsychological testing and imaging findings and 18 age-matched controls (aged 66.9 ± 10.3). CBF SPECT images were obtained with ^99mTc-hexamethyl propyleneamine oxime. On the reconstructed images, we obtained a linear regression equation between the cut-off values (from 35 to 50 %) and the number of voxels with a radioactivity exceeding the cut-off value transformed into natural logarithms, and then calculated the fractal dimension from the slope of the regression line thus obtained. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Results: The fractal dimensions were 1.084 ± 0.153 and 0.853 ± 0.062 (mean ± SD) in the VaD and control groups, respectively. The fractal dimension was significantly greater in the VaD group than in the control group (p < 0.0001). A significant negative correlation was observed between the fractal dimension and the MMSE score in the VaD group (r = 0.871, p < 0.0001). Conclusions: Because the CBF SPECT images of VaD patients showed a higher fractal dimension, these images were quantitatively more heterogeneous than those of age-matched controls. In the VaD group, cognitive function was shown to decline as the fractal dimension increased and images became more heterogeneous. Received: 20 June 2002, Received in revised form: 10 September 2002, Accepted: 16 September 2002 Correspondence to Takuya Yoshikawa, MD     

Cognitive profiles and regional cerebral blood flow patterns in dementia of the Alzheimer type

Individual cognitive profiles and correlations between cognitive functions and regional cerebral blood flow (rCBF) were analyzed in 20 consecutive patients with a clinical diagnosis of probable Alzheimer's disease (AD). CBF was measured with high resolution single photon emission computed tomography (SPECT) and [^99mTc]d,l-HMPAO. The analysis of cognitive profiles was based on the composite scores for six cognitive domains, derived from a detailed neuropsychological test battery, as compared with corresponding test data obtained in a control group of 28 age-matched healthy volunteers. The cognitive profiles displayed a marked heterogeneity as concerned the general level of cognitive impairment, the number of significantly affected cognitive domains, the spectrum of affected and non-affected cognitive domains, and the severity of each cognitive dysfunction. Statistically significant correlations with rCBF were found for memory scores (right frontal and temporal cortex), abstraction scores (frontal/parietal ratio of rCBF), language scores (left frontal and temporal cortex), visual perception scores (rCBF throughout the right hemisphere), and for visuo-construction scores (side-to-side asymmetry of parietal rCBF). We conclude that the previously observed topographical heterogeneity of rCBF distribution patterns in probable AD was reflected by differences in cognitive profiles. The observed heterogeneities stress the relevance of analyzing individual cognitive and rCBF data, as a supplement to group comparisons of data, in the investigation of diseases with potential heterogeneous affections of the brain.     

Depression in dementia of the Alzheimer type and in multi-infarct dementia

The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia.     

Sleep-wake cycles in multi-infarct dementia and dementia of the Alzheimer type

We monitored by actigraphs minute-by-minute activity of 10 patients with multi-infarct dementia (MID), 15 patients with dementia of the Alzheimer type (DAT), and 11 control volunteers for eight consecutive 24-hour periods to assess sleep-wake cycles and sleep quality. MID patients had disrupted sleep-wake cycles associated with decreased sleep quality. In contrast, ambulatory DAT patients maintained a relatively normal sleep-wake cycle that did not differ significantly from controls. There was no correlation between the severity of intellectual deterioration and the degree of sleep-wake cycle disintegration in either group of dementia patients.     

History of International Society for Cerebral Blood Flow and Metabolism

Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research.     

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 (Alzheimer's 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.     

Cerebral blood flow quantification using vessel-encoded arterial spin labeling

Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.     

Survival and cause of death in Alzheimer''s disease and multi-infarct dementia

Survival and causes of death of 218 patients with Alzheimer's disease (AD) and of 115 patients with multi-infarct dementia (MID) were examined. The patients were originally found in a community-based epidemiological survey of dementia, and all patients with AD or MID alive on the prevalence day were included. The 6-years survival rate for AD was 21.1% vs. the expected rate 48.5%, that for MID 11.9% vs. 45.2% expected. A comparison of relative survival rates suggested that MID carries a less favorable survival prognosis than AD. The mean durations were: AD 5.7 years and MID 5.2 years; median duration being 5 years in both diseases. The excess mortality in both AD and MID was independent of age. In AD, the survival rate decreased with increasing severity of dementia, while in MID the mortality was the same regardless of the severity of the dementia. The dementia disorder was the underlying cause of death in 68% of AD patients, and in 38% of MID patients, bronchopneumonia being the most frequent immediate cause of death in both groups. As a cause of death, acute cerebrovascular accidents occurred more often in MID patients than in the general population of comparable age. Malignant diseases were less frequent as a cause of death in both dementia groups than in the general population.