Alzheimer's disease: study by single photon emission tomography (Hm PAO Tc99m)

Single photon emission tomography with Hm PAO Tc99m was used in 27 patients with probable Alzheimer's disease, 9 patients with multi-infarct, dementia, and 11 healthy volunteers. The data were quantified in 4 regions of interest (using the basal ganglia as an internal standard): left and right prefrontal areas (Fg and Fd), and left and right parietal areas (Pg and Pd). Pg and Pd indices were lower in patients with Alzheimer's disease than in patients with multi-infarct dementia, and healthy volunteers (p less than 0.05). The ratio (Fd + Pd)/(Fg + Pg) was lower in patients with dressing apraxia (p less than 0.02), anosognosia (p less than 0.001), spatial agnosia (p less than 0.01), ideomotor apraxia (p less than 0.02), ideatory apraxia (p less than 0.01), and constructive apraxia (p less than 0.01). No correlation could be established between this ratio and the severity of aphasia, or between the indices and mini mental state scores. With Pg and Pd indices lower than 0.90, sensitivity for Alzheimer's disease was 70 p. 100 and specificity, 75 p. 100.     

Rates of decrease of cerebral blood flow in progressive dementias

To determine whether cerebral blood flow (CBF) progressively decreases as dementia progresses, we studied 133Xe washout at two or three different times in 23 demented patients. All 15 patients with Alzheimer's and 5 of 8 patients with vascular dementias had more rapid declines of CBF than did nondemented age-matched controls. Mean rate of change in Alzheimer's disease was -0.60 per month, compared with +0.29 per month in four controls tested twice. Regression analysis of CBF with age in 30 controls tested once showed a decline of CBF with aging at a rate of -0.013 per month. The rates of CBF decline in dementia were significantly correlated with rates of change of behavioral score measuring functional impairment.     

CSF somatostatin-like immunoreactivity in dementia

Concentrations of somatostatin-like immunoreactivity (SLI) in CSF were reduced in Alzheimer's disease (AD) and multi-infarct dementia (p less than 0.01), but not in normal-pressure hydrocephalus, Parkinson's disease, and Huntington's disease. This suggests that reduced SLI content in AD cerebral cortex is reflected in CSF. Chromatographic characterization of CSF SLI showed no differences between AD and controls. Concentrations of SLI in AD patients overlapped those in both normal subjects and patients with multi-infarct dementia, so that changes in CSF SLI have no diagnostic specificity.     

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.     

Cerebrospinal fluid neuron-specific enolase is decreased in multi-infarct dementia, but unchanged in Alzheimer''s disease.

Cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) were measured in 22 patients with probable Alzheimer's disease and in 35 patients with multi-infarct dementia, and in 15 controls. CSF NSE in patients with Alzheimer's disease did not differ from those in controls. In patients with multi-infarct dementia without recent vascular events CSF NSE was lower than in controls or in Alzheimer patients. This finding is in accord with the prevailing opinion that vascular dementia is caused by multiple infarcts and not by continuous neuronal ischaemia.     

Computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia. A prospective clinicopathologic study

The accuracy of computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia was studied prospectively. Out of 50 demented patients, autopsy revealed 32 cases with either senile dementia of the Alzheimer's type (SDAT), multi-infarct dementia (MID), or a combination of both. Eighteen patients had dementia caused by other diseases. Based on a combination of computed tomography, electroencephalography, and clinical features, senile dementia of the Alzheimer's type was differentiated from all 50 patients, with a specificity of 83% and a sensitivity of 80%. Focusing on senile dementia of the Alzheimer's type, multi-infarct dementia, or a combination of both, specificity decreased to 65% and sensitivity to 47%. Comparing the different methods, multi-infarct processes were diagnosed with a higher sensitivity by the clinical features (73%) than by computed tomography (18%) or electroencephalography (18%). None of the methods validly differentiated multi-infarct dementia from a combination of multi-infarct dementia and senile dementia of the Alzheimer's type.     

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.     

Regional cerebral blood flow study with 99mTc-hexamethyl-propyleneamine oxime single photon emission computed tomography in Alzheimer's and multi-infarct dementia

Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia.     

The nucleus basalis of Meynert in multi-infarct (vascular) dementia

Summary The number and nucleolar volume of nerve cells within the nucleus basalis of Meynert were estimated in 10 patients with Alzheimer's disease, 12 with multi-infarct dementia, 9 with a mixed Alzheimer/multi-infarct dementia and in 10 age-matched controls. As reported previously in Alzheimer's disease, both the number and nucleolar volume of surviving cells was reduced, whereas in multi-infarct dementia no significant change in either measure was noted. In patients with Alzheimer's disease/multi-infarct dementia the loss of nerve cells and reduction in nucleolar volume varied greatly in severity from patient to patient according to the relative balance of Alzheimer and vascular type pathological changes present within each patient.Supported in part by a grant from the North Western Regional Health Authority to one of us (BM)     

Increased cytosolic free calcium in lymphocytes of Alzheimer patients.

Free cytosolic calcium content [Ca2+]i was determined in peripheral blood mononuclear cells (PBMC) from healthy volunteers, Alzheimer's disease and multi-infarct dementia patients. Measurement of [Ca2+]i by the fluorescent dye quin-2, before and at several time intervals during incubation with phytohemagglutinin (PHA), showed a higher resting [Ca2+]i in PBMC of Alzheimer's disease patients as compared to controls and multi-infarct dementia patients. However, the addition of supra-optimal PHA doses (100 micrograms/ml) induced strikingly higher [Ca2+]i levels in Alzheimer's disease patients (1647 +/- 200 nM versus 398 +/- 27 nM in controls, and 346 +/- 40 nM in multi-infarct dementia patients). The increased [Ca2+]i concentration was also found after a specific stimulation with a monoclonal anti-CD3 antibody. The results may have important implications in understanding the pathophysiology of Alzheimer's disease and suggest that [Ca2+]i may prove diagnostically valuable.     

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.     

Prevalence of clinically diagnosed Alzheimer's disease and other dementing disorders: a door-to-door survey in Appignano, Macerata Province, Italy

The purpose of this study was to investigate the prevalence of dementia in an Italian population using a door-to-door 2-phase design. As part of a social and health survey, we administered the Hodkinson abbreviated mental test to all persons over age 59 residing in the Commune of Appignano on January 1, 1987 (N = 778). We then investigated all subjects scoring 7 or less on the cognitive test following a standardized diagnostic protocol. We found 48 patients affected by dementia, yielding a crude prevalence ratio (cases per 100 population over age 59) of 6.2; prevalence ratios were 2.6 for Alzheimer's disease, 2.2 for multi-infarct dementia, 0.8 for mixed dementia, 0.4 for secondary dementia, and 0.3 for unspecified dementia. Age- and sex-specific prevalence ratios increased steeply with age and were consistently higher in women for Alzheimer's disease and in men for dementia of all types and multi-infarct dementia. Alzheimer's disease was slightly more frequent than multi-infarct dementia; however, the most common type of dementia varied across age groups. Most cases of Alzheimer's disease were sporadic and had a late age of onset. Comparison with other populations suggests that dementia of all types is as frequent in Appignano as elsewhere, and that Alzheimer's disease might be more frequent in rural than in urban populations.     

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

IntroductionWe aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.MethodsThe study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.ResultsCompared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRS_total: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).ConclusionsEarly cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.     

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.     

Glutamate uptake is decreased in platelets from Alzheimer's disease patients

Because excitotoxicity may be involved in neurodegeneration in Alzheimer's disease, we investigated possible modifications of platelet glutamate uptake in AD patients. High-affinity glutamate uptake was studied in platelets from 35 Alzheimer's disease patients, 10 multi-infarct dementia patients, and 35 age-matched normal controls; it was decreased by 40% in platelets from Alzheimer's disease patients compared with controls and with multi-infarct dementia patients. Platelet glutamate uptake could be used as peripheral marker of glutamatergic involvement and as adjunctive diagnostic tool in Alzheimer's disease patients.     

Cerebral blood flow and cerebral oxygen metabolism in patients with dementia of frontal lobe type

This study was designed to investigate the differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) between patients with dementia of frontal lobe type and patients with Alzheimer's disease. Positron emission tomography (PET) using 15O steady state inhalation technique was carried out in 5 patients with a clinical diagnosis of dementia of frontal lobe type and 7 patients with a clinical diagnosis of Alzheimer's disease. CBF and CMRO2 were significantly decreased in the frontal cortex except for precentral region in patients with dementia of frontal lobe type in comparison to those values in patients with Alzheimer's disease. However, in patients with dementia of frontal lobe type CBF and CMRO2 in the parietal cortex and the occipital cortex were relatively preserved when compared with patients with Alzheimer's disease. In comparison with values for CBF and CMRO2 in the posterior part of brain [frontal or temporal/(parietal + occipital)/2 ratio], both values in the frontal cortex were markedly decreased in all 5 patients with dementia of frontal lobe type, but there was no marked reduction in the frontal cortex in patients with Alzheimer's disease. In addition, in 2 patients with dementia of frontal lobe type whose duration of the disease was more than 7 years, CBF and CMRO2 in the temporal cortex were markedly reduced in comparison with values in the posterior part of brain. These results suggested that PET findings of marked reduction in CBF and CMRO2 in the frontal cortex are useful to distinguish dementia of frontal lobe type from Alzheimer's disease.     

Elevated cerebrospinal fluid lactic acid levels in Creutzfeldt-Jakob disease

The concentration of cerebrospinal fluid (CSF) lactic acid was determined in three patients with biopsy proven Creutzfeldt-Jacob disease (CJD). When compared with twenty demented patients diagnosed as having either Alzheimer's disease or multi-infarct dementia, the CSF lactic acid values of the CJD patients were significantly elevated (p less than .001). Elevated CSF lactic acid levels may be an important biochemical marker of CJD and useful in the differential diagnosis of dementia.     

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).     

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.     

Computed tomography findings in senile dementia and normal aging.

Computed tomography (CT) findings in 57 patients with senile dementia of Alzheimer type (SDAT), 19 patients with multi-infarct dementia and 85 controls of similar age and sex were studied. The SDAT patients differed from the controls of ventricular dilatation, frontal horn index, cella media index and the width of the third ventricle, and also in the index of cortical atrophy. Even the least severely demented SDAT patients differed from the controls. In the SDAT group with the increasing degree of intellectual impairment the ventricular dilatation increased, but cortical atrophy did not correlate with the psychological test score. The multi-infarct dementia patients differed from the controls in all CT variables including local changes. The SDAT patients had a more marked ventricular dilatation than the multi-infarct dementia patients. The multi-infarct dementia patients had more frequently local changes in SDAT patients. In the control group age correlated with ventricular dilatation, and the lower test scores correlated with cortical atrophy in the left temporal region.