Twenty patients diagnosed as having multiple sclerosis (MS) were examined by MRI and 9 neuropsychological scales: MMSE, BCRS, RMB, SDMT, BNT, VM, FAS, Benton and Hamilton. The number and distribution of the lesions, and...Twenty patients diagnosed as having multiple sclerosis (MS) were examined by MRI and 9 neuropsychological scales: MMSE, BCRS, RMB, SDMT, BNT, VM, FAS, Benton and Hamilton. The number and distribution of the lesions, and cerebral and corpus callosum atrophy were evaluated by MRI. MR images were generated by a 0.5 Tesla instrument utilizing T1WI, PD and T2WI imaging techniques. The results reveal (1) that patients with MS are impaired in a broad range of cognitive functions but mainly memory is affected; (2) number of lesions in the corona radiata, insula and hippocampus is correlated with cognitive impairment, and (3) enlargement of the IIIrd ventricle is an indicator of memory impairment in MS patients.
This study presents a structural and clinical description of a patient with dementia of motor neuron disease (D-MND), and compares and contrasts the neuropsychological characteristics of this patient with those of a grou...This study presents a structural and clinical description of a patient with dementia of motor neuron disease (D-MND), and compares and contrasts the neuropsychological characteristics of this patient with those of a group of patients with Alzheimer's disease (AD) matched by severity of dementia. The D-MND patient as well as the AD patients performed abnormally on all tasks that assessed executive/frontal functions. However, the D-MND patient tended to be more impaired than AD patients on tasks that required high speed decisions and on shifting from one strategy to another. Deficits in memory, language, and lexical-semantic abilities were also apparent in this patient. The co-occurrence of signs and symptoms characteristics of 'subcortical' dementia with those of 'cortical' dementia suggest that the executive system dysfunction may be secondary to subcortical pathology.
Regional cerebral glucose metabolism (rCMRG1) measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval ranging from 6 to 27 months) in 25 patients with probable Alzh...Regional cerebral glucose metabolism (rCMRG1) measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval ranging from 6 to 27 months) in 25 patients with probable Alzheimer's disease (AD). A significant decline of rCMRG1 was noted in the whole brain (p = 0.02) which was most pronounced in the temporoparietal (p = 0.002), frontal (p = 0.01), superior parietal (p = 0.01) and occipital (p = 0.03) association cortex. A similar decline was also present in the thalamus (p = 0.04) but not in the primary visual and sensorimotor cortex, basal ganglia, cerebellum and brainstem. The changes of rCMRG1 in the temporoparietal, frontal and occipital association cortex were related to the change of the Mini Mental State Examination score (temporoparietal: r = 0.49, p = 0.01; frontal: r = 0.40, p = 0.05; occipital: r = 0.44, p = 0.03). The rate of clinical and metabolic decline was not related to age at onset, sex, family history or duration of disease. The results suggest that clinical deterioration and metabolic impairment in probable AD are closely related and dependent on progression of pathological changes in cortical association areas.
A random sample (n = 101,104) was taken from total general hospital admissions to Scottish hospitals (1:25 fraction) during the period 1968-1977. Record linkage was used to connect general hospital and psychiatric hospit...A random sample (n = 101,104) was taken from total general hospital admissions to Scottish hospitals (1:25 fraction) during the period 1968-1977. Record linkage was used to connect general hospital and psychiatric hospital morbidity records (SMR 1 and SMR 4). Patients with a subsequent admission with dementia (principal diagnosis ICD 9,290) were identified from the general hospital sample on follow-up. Age-specific first-admission rates for dementia were calculated for the hospital population considered. First-admission rates ranged from 41.9 (per 100,000 person-years-at-risk, PYR) for male patients aged 60-64 years to 514.2 in the age band 80 years and over. The equivalent figures for female patients were 40.8 (per 100,000 PYR) and 723.1. Epidemiological research has shown an approximate doubling of prevalence rates every 5 years after the age of 60 years, and the age-banded hospital admission rates in the present study are consistent with this underlying pattern. Expected first-admission rates in dementia were calculated from admission rates in dementia and community prevalence reported in previous studies. Expected rates were contrasted with the rates observed in the present study. An estimated 6-7% of prevalent dementia cases and between 11 and 14% of 'expected dementia admissions' achieved a recorded main diagnosis of dementia, and proportions were stable across age bands in the case of both measures. The wide discrepancy between expected and observed admission rates suggests relative underreporting of dementia as a principal diagnosis in hospital statistics.
In an attempt to evaluate EEG changes associated with dementia in Parkinson's disease (PD), we performed frequency analysis in three groups of 10 subjects each; two with PD, and one normal control group. The PD patient g...In an attempt to evaluate EEG changes associated with dementia in Parkinson's disease (PD), we performed frequency analysis in three groups of 10 subjects each; two with PD, and one normal control group. The PD patient groups were matched for age, sex, severity and duration of disease, but were discordant for the existence of dementia. Normals were age- and sex-matched healthy volunteers. The relative alpha amplitude was significantly decreased in the demented PD patients, unrelated to motor disability. There was a nonsignificant but consistent trend of increased amplitude in the delta and theta range in the demented PD patients as compared to nondemented PD subjects and normal controls, as well as increased amplitude in the theta and delta range with more severe motor disability in the nondemented PD patients.
In order to evaluate possible progression in the severity of their cognitive impairment, 34 parkinsonians with intellectual impairment were followed longitudinally for 7 years. Each patient was matched for age, sex, seve...In order to evaluate possible progression in the severity of their cognitive impairment, 34 parkinsonians with intellectual impairment were followed longitudinally for 7 years. Each patient was matched for age, sex, severity and duration of illness, and pharmacological treatment, with a parkinsonian patient without cognitive impairment. Results suggest that cognitive deficits are not static but rather there is a progression in the severity. Furthermore, patients suffering from severe dementia are more likely to die during the follow-up period. The prognosis of Parkinson's disease seems to be changed substantially by the occurrence of dementia. The natural history of parkinsonian dementia does not seem to differ from the history of other forms of dementia with a progressively disabling course leading to a complete loss of autonomy.
The prevalence of dementia, assessed on the basis of the Wechsler scale (WAIS), was determined in a group of 88 patients with idiopathic Parkinson's disease (PD) lasting longer than 4 years. In this group, 19 patients (2...The prevalence of dementia, assessed on the basis of the Wechsler scale (WAIS), was determined in a group of 88 patients with idiopathic Parkinson's disease (PD) lasting longer than 4 years. In this group, 19 patients (22%) were diagnosed as demented. They were significantly older at the time of evaluation (72.9 +/- 8.1 vs. 63.6 +/- 11.9), and also at the onset of the disease (61.1 +/- 10.6 vs. 54.4 +/- 12.1) than nondemented patients. Their parkinsonism, as judged on the base of the Activity of Daily Living Scale, was more pronounced (57.4 +/- 13.7 vs. 73.3 +/- 15.6) and they developed psychotic side-effects of L-DOPA treatment (53% vs. 9%) more often. A weak negative correlation between age and intellectual quotient (IQ) was found, and a much stronger positive correlation between education and IQ. 25 patients of those diagnosed previously as non-demented were reassessed for dementia after another 5 years of disease. Only two of them were found demented. Both died and an immunohistochemical study of their brains was performed. In the 2 cases we found neuropathological features of both PD (Lewy bodies) and Alzheimer's disease (AD)--neurofibrillary tangles (NFT) and senile plaques (SP). This finding may support the hypothesis that, at least in some cases, dementia in PD could be due to an accompanying AD.
The density of diffuse, primitive and classic beta/A4 protein deposits was estimated in sulci and gyri in the frontal cortex and parahippocampal gyrus (PHG) in 8 cases of Alzheimer's disease. Total beta/A4 deposit densit...The density of diffuse, primitive and classic beta/A4 protein deposits was estimated in sulci and gyri in the frontal cortex and parahippocampal gyrus (PHG) in 8 cases of Alzheimer's disease. Total beta/A4 deposit density was similar in the frontal cortex and PHG but the ratio of primitive and classic deposits to the total was greater in the PHG compared with the frontal cortex. Total beta/A4 deposit density was greater in the depths of the sulci, but the proportions of the various beta/A4 subtypes were similar in sulci and gyri. Hence, increased density of primitive and classic deposits in the PHG could reflect enhanced conversion of diffuse to mature deposits whereas increased density of mature beta/A4 subtypes in sulci versus gyri may reflect increased beta/A4 deposition in the sulci.
It is generally accepted that presenile Alzheimer's disease (AD) has faster progression and severer clinical manifestation than senile onset AD. Recently a relative left frontal hypoperfusion was only found in patients w...It is generally accepted that presenile Alzheimer's disease (AD) has faster progression and severer clinical manifestation than senile onset AD. Recently a relative left frontal hypoperfusion was only found in patients with presenile AD by using SPECT imaging. The aim of the present report was to ascertain whether the same conclusion could be drawn matching the population with respect to the severity of the cognitive profile and disease duration. Twenty subjects for each group were studied with SPECT and no differences emerged between groups. It is postulated that presenile and senile onset AD represent aspects of the same biological process.
We reconstructed three-dimensional (3D) surface images from data from single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]-iodoamphetamine (123I-IMP) in 29 patients with Parkinson's disease, 16 pat...We reconstructed three-dimensional (3D) surface images from data from single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]-iodoamphetamine (123I-IMP) in 29 patients with Parkinson's disease, 16 patients with Alzheimer's disease and 11 normal control subjects. In patients with nondementing Parkinson's disease, perfusion defects were frequently found in the parietal cortical region at a threshold value of 65%. In demented Parkinson's disease patients, perfusion defects were frequently noted at threshold of 45-65%, and were more marked in the bilateral temporal and parietal cortices. In Alzheimer's disease, perfusion defects were similar to those found in dementing Parkinson's disease. These results suggest that dementia in Parkinson's disease is related to the perfusion reduction of the temporoparietal cortex, and may support the view that Parkinson's disease and Alzheimer's disease overlap in some patients. A 3D display of an 123I-IMP brain tomogram may be useful for detecting cortical lesions in patients with dementia or cognitive impairment.
408 elderly primary care attenders were screened using the Geriatric Depression Scale (GDS) and the 30-item General Health Questionnaire (GHQ). 36% were identified as 'cases' on the GDS and 32% on the GHQ. The 'cases' an...408 elderly primary care attenders were screened using the Geriatric Depression Scale (GDS) and the 30-item General Health Questionnaire (GHQ). 36% were identified as 'cases' on the GDS and 32% on the GHQ. The 'cases' and a random sample of 'non-cases' were interviewed using the Geriatric Mental State Examination (GMS), the Bedford College Life Events and Difficulties Interview (LEDS), the National Adult Reading Test (NART), and systematic inquiry concerning physical health. Sensitivity and specificity of the GDS were 85% and 68%, and of the GHQ 77% and 67%. General practitioner identification of cases showed a sensitivity of 78% and a specificity of 60% against the GMS. Depression was significantly associated with life events, chronic difficulties, poor physical health and current lack of a confiding relationship. Subjective complaints of depression were associated with low premorbid intelligence and lifelong lack of a confiding relationship. The availability of a confiding relationship appears to have a protective effect against depressive illness associated with life events and chronic difficulties.
In order to investigate neuropsychological differences in patients with mild AD, we carried out a pilot study on 28 patients with a clinical diagnosis of mild dementia (CDR: 0.5-1) using an extensive neuropsychological b...In order to investigate neuropsychological differences in patients with mild AD, we carried out a pilot study on 28 patients with a clinical diagnosis of mild dementia (CDR: 0.5-1) using an extensive neuropsychological battery, in comparison with 28 normal controls. The results of a cluster analysis, applied on the neuropsychological variables, showed the existence of at least two main subgroups of patients. Cluster 1 patients had a mean age of 61.1 years and showed a greater impairment on measures of language, abstract reasoning and verbal fluency; cluster 2 patients, with a mean age of 72.0, had more severe impairment in memory function. These preliminary results may suggest the existence of different subtypes of AD characterized by selective neuropsychological deterioration in the early stages of the disease.
There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age...There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years) and 15 AD patients (age 61-78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 microgram/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 microgram/l). IGF-I levels were lower (p < 0.005) in elderly (73.9 +/- 8.2 microgram/l) and in AD subjects (108.0 +/- 5.9 micrograms/l) than in young subjects (288.7 +/- 22.1 micrograms/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 micrograms/l) and in AD subjects (437.6 +/- 93.5 micrograms/l/h) were lower (p < 0.01) than in young subjects (658.6 +/- 100.1 micrograms/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2 micrograms/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 +/- 245.6 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)
Heparan sulfate (HS), along with serum amyloid P component, has been identified in all types of amyloid investigated so far, regardless of the type of amyloid protein deposited. To assess whether unique or specific HS pr...Heparan sulfate (HS), along with serum amyloid P component, has been identified in all types of amyloid investigated so far, regardless of the type of amyloid protein deposited. To assess whether unique or specific HS proteoglycans (HSPGs) may be involved in the formation of these lesions, we have investigated the accumulation of several distinct HSPG epitopes in the cerebra of patients with different forms of neurodegenerative disease. A panel composed of several antibodies revealed distinctive patterns of HSPG accumulation. In patients with dementia of the Lewy body type, the burned-out-type plaques and preamyloid-type plaques were strongly stained by both the anti-HS 'chain' and anti-HS 'stub' antibodies, but by none of the available anti-core protein antibodies. In Alzheimer's disease, the preamyloid-type plaques, dense-cored-type plaques, neuritic-type plaques and the neurofibrillary tangles were stained by the anti-'stub' antibody. The anti-'chain' and the anti-core protein antibodies, in contrast, failed to stain the preamyloid-type plaques and burned-out-type plaques, but stained the neuritic-type plaques in these patients. These data suggest differences in the types of HS and HSPG (fragments) that accumulate in amyloid lesions that may hallmark neurodegenerative disorders of different etiologies.
Primary neuronal cell cultures from P6 mice were investigated in order to study amyloid protein precursor (APP) gene expression in differentiating neurons. Cerebellar granule cells which strongly express APP 695 allowed...Primary neuronal cell cultures from P6 mice were investigated in order to study amyloid protein precursor (APP) gene expression in differentiating neurons. Cerebellar granule cells which strongly express APP 695 allowed the identification of three distinct isoforms of neuronal APP 695. The high-molecular-weight form of APP 695 is sialylated. The expression pattern of neuronal APP 695 changes during in vitro differentiation. Sialylated forms become more abundant upon longer cultivation time. The secreted forms of sialylated, neuronal APP 695 are shown to comigrate with APP isolated from cerebrospinal fluid. We suggest that the different sialylation states of APP 695 may reflect the modulation of cell-cell and cell-substrate interactions during in vitro differentiation and regeneration.
The stunning accumulation of data on the physiopathology of Alzheimer's disease is a real hinderance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cum...The stunning accumulation of data on the physiopathology of Alzheimer's disease is a real hinderance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cumbersomeness and cost of clinical trials in that field, a review of potential targets for drugs that are supposed to be active against the disease has become necessary, for a true definition of the rational justifications of trials to be envisaged.
General cognitive function and specific language and memory processing abilities were compared in dementia of the Alzheimer type (DAT), depressed and normal control subjects. Several tests clearly differentiated between...General cognitive function and specific language and memory processing abilities were compared in dementia of the Alzheimer type (DAT), depressed and normal control subjects. Several tests clearly differentiated between DAT and depressed subjects including a verbal fluency task, several components of a word memory test, an IQ deterioration index, and the Mini-Mental State Examination. The inability of DAT subjects to take advantage of semantic cues in both the verbal fluency and in the memory test contrasted with the performance of depressed and normal subjects, who were able to benefit from semantic cues. Depressed patients displayed deficits compared with normal controls on the more effortful verbal fluency task but not on the memory test. Tasks that are least effortful, rely on semantic associations, and require declarative memory are most likely to discriminate between DAT and depression.
We studied the correlation between the caregiver's feelings of burden and the cognitive, behavioral and functional impairment of demented patients. We attempted to show the influence of caregiver's feelings of burden on...We studied the correlation between the caregiver's feelings of burden and the cognitive, behavioral and functional impairment of demented patients. We attempted to show the influence of caregiver's feelings of burden on their perception of the patients' functional status and to establish the predictors of feelings of burden. Twenty-five probable Alzheimer disease patients (NINCDS-ADRDA criteria) were assessed on cognitive measures and functional status (DAFS). The caregiver's index of burden (CIB), obtained from an adapted version of the Zarit Burden Interview, was correlated with the caregiver's report on the patient's instrumental activities of daily living (IADL) and physical self-maintenance functions (ADL); total and partial DAFS scores, and patient's cognitive and behavioral problems rated with the Functional Dementia Scale (FDS). The CIB correlated with the caregiver's report on the patient's behavioral disturbances (r = 0.71, p < 0.001) and physical self-maintenance activities (r = 0.62, p < 0.001), but not with cognitive impairment, IADL and the DAFS. The patients showed better functional performance in the direct assessment than in that reported by their caregivers (mainly in shopping, feeding, dressing, and ambulation). Thus, burden may foster a growing intolerance of the caregiver, inducing an underestimation of the patient's actual functional competence. The caregiver's report on the patient's behavioral problems was the best predictor of feelings of burden (P = 19,9, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
An investigation was carried out of psychiatric and behavioural symptoms in non-demented and demented subjects derived from a population study of the very elderly. Information on psychiatric and behavioural symptoms came...An investigation was carried out of psychiatric and behavioural symptoms in non-demented and demented subjects derived from a population study of the very elderly. Information on psychiatric and behavioural symptoms came from two independent sources: a physician's examination and an interview with an informant. The symptoms were grouped into clusters using principal-components analysis. Little agreement was found between the two sources of information on symptoms of anxiety, depression and psychosis. However, there was agreement about an increase in inactivity symptoms as the severity of dementia increased.
Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilateral nucleus basalis of Meynert (nbM) lesions; 10 additional animals served as sham controls. Eight to ten days later, subjects with lesions received ei...Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilateral nucleus basalis of Meynert (nbM) lesions; 10 additional animals served as sham controls. Eight to ten days later, subjects with lesions received either fetal cholinergic transplants implanted within the ipsilateral (relative to the lesion) frontal cortex or control transplant surgeries. Lesioned animals with and without transplants were then treated with GM1 (20 mg/kg, i.p.) for either 0, 1 or 10 days and were then trained and tested for 72-hour retention of passive avoidance. Results indicated that the lesion produced a significant impairment on this task. Transplant therapy combined with GM1 for 10 days yielded a significant reversal of this deficit. GM1 injections continued once per week for 4 weeks for half the lesioned animals in the transplant and no-transplant 10-day conditions. During a 6-month period, all subjects were assessed on two additional memory tasks (complex spatial discrimination and delayed spatial alternation). In general, there was no indication of a lesion, transplant, GM1, or transplant X GM1 effect on these tasks. Approximately 7.5 months after transplants, subjects were sacrificed and their frontal cortices examined for choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activity. Only lesioned subjects with transplants which were given sustained GM1 treatment (i.e., 10 days plus weekly injections for 4 weeks) showed significant attenuations of lesion-induced CAT and AChE depletions. These data suggest that a combined treatment strategy of fetal transplant plus GM1 is capable of reversing nbM lesion-induced memory and neurochemical deficits in an animal model of the cholinergic deficits in Alzheimer's disease.