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PubMed1995

Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia.

Relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in alpha 1M and UT levels and alpha 1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between alpha 1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls (P < 0.05). A tendency towards a negative correlation between alpha 1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between alpha 1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of alpha 1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.

Aged↗
PubMed1984

Dementia of the Alzheimer type and multi-infarct dementia: a clinical description and diagnostic problems.

Patients who had Alzheimer's disease-senile dementia of the Alzheimer type (AD/SDAT) or multi-infarct dementia (MID) were compared with a group of controls. Demented patients had approximately the same degree of dementia and the same duration of illness. The MID group had a significantly higher mean age than the AD/SDAT group. Sixty-three per cent of the AD/SDAT patients were free of other diseases, while 65 per cent of the MID patients had cardiovascular disease. Thirty per cent of the MID patients had a history of previous depression, while only 5 per cent of the AD/SDAT patients had had depression. At the time of the investigation, however, AD/SDAT patients showed significantly more signs of depression than the MID patients. Focal neurologic signs were found in 70 per cent of the MID patients and only 6 per cent of the AD/SDAT patients. The electrocardiogram was normal for every AD/SDAT patient, while 75 per cent of the MID patients had abnormal ECGs. Electroencephalography showed generalized slow frequencies in 79 per cent of the AD/SDAT patients and localized slow frequencies and abnormalities in 65 per cent of the MID patients. Computed tomography of the brain showed that MID patients had significantly greater dilation of the ventricular system, while cortical atrophy did not differ significantly among the three groups. Homovanillic acid in the cerebrospinal fluid was significantly lower in the AD/SDAT group as compared with controls.

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PubMedDate not supplied

Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia.

The phenotypes of apolipoprotein E (ApoE) in the plasma of patients with dementia of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the control subjects, the frequency of the ApoE epsilon 4 allele was significantly higher in the DAT group as well as the VD group, but was not significantly different in the cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE mRNA level in the DAT group and the VD group was significantly lower than that in the control group. These findings suggest that the phenotype of ApoE is associated with DAT and VD, and that the lower level of ApoE mRNA may play an important role in the development of DAT as well as VD.

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PubMed1988

Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia.

Monoamine oxidase-B (MAO-B) activity of platelets of an age- and sex-matched group of controls was compared with several groups of inpatients having non-familial dementia of Alzheimer type (DAT), Parkinson's disease (PD), multi-infarct dementia (MID), mixed types of these 3 diseases and a group of other central nervous system (CNS) organic disorders. All patients were subjected to several psychometric tests, including the Sandoz Clinical Assessment--Geriatric Scale, Hamilton Rating Scale for Depression, Mini-Mental State Examination and the Organic mental Disorder Scale (OMDS). A statistically significant enhancement of MAO-B activity could be observed in DAT patients and in PD patients, whereas the MID group showed a mean activity similar to that of the control group and the group with other organic CNS disorders. In DAT patients the degree of dementia in the OMDS test and the enhancement of MAO activity were positively correlated, but PD did not show such a correlation. It is concluded that the increase of MAO activity in PD and in DAT might be due to a disease-related enhanced affinity to oxygen and to such oxygen-derived radicals as superoxide or hydroxyl radicals. However, a possible drug-induced enhancement of MAO activity in PD cannot be excluded. Furthermore, the MAO-B activity values in platelets of individual patients or controls are not indicative of diagnosis or prognosis of any of these diseases and are of no disease-related specificity.

Adult↗
PubMed1989

Magnetic resonance imaging in Alzheimer's disease, multi-infarct dementia, alcoholic dementia and Korsakoff's psychosis.

Regional spin lattice relaxation times (T1) measured during nuclear magnetic resonance imaging of the brain were compared in patients with Alzheimer's disease, multi-infarct dementia, alcoholic dementia, Korsakoff's psychosis and control subjects. Regional differences were found between all patient groups compared with controls and within patient groups, with the exception of the comparison between Korsakoff's psychosis and alcoholic dementia. Correlations between regional T1 change and cognitive test scores were also found, with particular emphasis between visuospatial deficits and parietal T1. The possible role of T1 measures in the pathophysiology of these disorders is discussed.

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PubMed1990

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.

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PubMed1991

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.

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PubMed1998

Dementia with Lewy bodies. A distinct non-Alzheimer dementia syndrome?

Lewy body formation is central to the pathological phenotype of a spectrum of disorders. The most familiar of these is the extrapyramidal syndrome of idiopathic Lewy-body Parkinson's disease (PD). Studies of dementia in the elderly suggest that another manifestation of Lewy body pathology is equally or more common than Parkinson's disease. This syndrome of Dementia with Lewy bodies (DLB) has been given a number of diagnostic labels and is characterised by dementia, relatively mild parkinsonism, visual hallucinations, and fluctuations in conscious level. Although many of these features can arise in Parkinson's disease, the patients with DLB tend to have early neuropsychiatric features which predominate the clinical picture, and the diagnosis of the syndrome in practice is more concerned with the differential diagnosis of Alzheimer's disease (AD). Distinction from AD has clinical importance because of potentially differing therapeutic implications. Diagnostic guidelines for the clinical diagnosis and pathological evaluation of DLB are reviewed. Research into the disorder has centered around characterising the clinical, neuropsychological, pathological, neurochemical and genetic relationships with Alzheimer's disease on the one hand, and Parkinson's disease on the other. Many cases of DLB have prominent pathological features of AD and there are some shared genetic risk factors. Differences from the pathology of PD are predominantly quantitative rather than qualitative and evidence is discussed which suggests that DLB represents a clinicopathological syndrome within the spectrum of Lewy body disorders. The possibility that the syndrome represents a chance association of PD and AD is not supported by published studies.

Alzheimer Disease↗
PubMed1998

Dementia of frontal type and dementias with subcortical gliosis.

The group of Frontotemporal dementias (FTD) is composed of non-Alzheimer forms of dementia characterized clinically by behavioural and personality change leading to apathy and mutism. The disorder is associated with a progressive atrophy of the frontal, anterior temporal and anterior parietal lobes of the brain with several types of underlying pathology. One type (frontal lobe degeneration) is characterized by a microvacuolar degeneration of the outer cortical laminae along with a mild and mainly subpial gliosis and a loss of nerve cells, mostly from layers II and III. Another type shows transcortical tissue cavitation and florid gliosis with neuronal degeneration characterized by the presence of tau and ubiquitin positive inclusion bodies and alpha beta-crystallin-positive ballooned neurones: such changes have been termed 'Pick-type histology', and form the basis for the modern definition of 'Pick's disease'. The aetiological relationship between these two histological types is presently unknown. Both histologies can be differently distributed topographically throughout the brain to produce syndromes of progressive language disorder, when affecting bitemporal lobes or the left hemisphere preferentially, or progressive apraxia when parietal and motor regions are involved. Either pathology can be combined with or overlaps with that of classical motor neurone disease to produce motor neurone disease dementia. The underlying cause of FTD is unknown but genetic factors are strongly implicated. About half of cases show a previous family history of a similar disorder. In several families bearing a FTD clinical and pathological phenotype, linkage to chromosome 17 has been established but the pathology of this group appears distinctive and its relation to other forms of FTD awaits further elucidation. It is still possible that the many clinical and pathological variants of FTD may reflect different phenotypic expressions of a particular genetic change(s) at a single locus on this chromosome.

Cerebral Cortex↗
PubMed2000

Aberrant splicing of tau pre-mRNA caused by intronic mutations associated with the inherited dementia frontotemporal dementia with parkinsonism linked to chromosome 17.

Frontotemporal dementia accounts for a significant fraction of dementia cases. Frontotemporal dementia with parkinsonism linked to chromosome 17 is associated with either exonic or intronic mutations in the tau gene. This highlights the involvement of aberrant pre-mRNA splicing in the pathogenesis of neurodegenerative disorders. Little is known about the molecular mechanisms of the splicing defects underlying these diseases. To establish a model system for studying the role of pre-mRNA splicing in neurodegenerative diseases, we have constructed a tau minigene that reproduces tau alternative splicing in both cultured cells and in vitro biochemical assays. We demonstrate that mutations in a nonconserved intronic region of the human tau gene lead to increased splicing between exon 10 and exon 11. Systematic biochemical analyses indicate the importance of U1 snRNP and, to a lesser extent, U6 snRNP in differentially recognizing wild-type versus intron mutant tau pre-mRNAs. Gel mobility shift assays with purified U1 snRNP and oligonucleotide-directed RNase H cleavage experiments support the idea that the intronic mutations destabilize a stem-loop structure that sequesters the 5' splice site downstream of exon 10 in tau pre-mRNA, leading to increases in U1 snRNP binding and in splicing between exon 10 and exon 11. Thus, mutations in nonconserved intronic regions that increase rather than decrease alternative splicing can be an important pathogenic mechanism for the development of human diseases.

Adult↗
PubMed2002

Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.

OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.

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PubMedDate not supplied

Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia.

The association between the estrogen receptor (ER-alpha) gene and dementia was examined in 223 patients with Alzheimer's disease (AD), 66 with vascular dementia (VD), 17 with alcohol-associated dementia (ALD) and 134 healthy elderly control subjects. The PvuII and XbaI restriction fragment length polymorphisms of the ER-alpha gene were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of restriction sites and small letters the presence of restriction sites. We found that the frequency of the ER-alpha gene P allele and X allele in the late-onset AD (LOAD) group (P allele was 0.51, X allele was 0.30) was significantly higher than that in controls (P 0.38, p < 0.01; X 0.20, p < 0.01), and that the frequency of the ER-alpha gene P allele and PP genotype was significantly different between apolipoprotein E epsilon4 carriers and noncarriers in LOAD. These findings suggest that the genotype of the ER-alpha gene may be specific in LOAD, and that the ER-alpha gene was an additional risk for LOAD.

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PubMedDate not supplied

Frontotemporal dementia can be distinguished from Alzheimer's disease and subcortical white matter dementia by an anterior-to-posterior rCBF-SPET ratio.

Sixteen patients with frontotemporal dementia (FTD), 27 with early-onset Alzheimer's disease, 25 with late-onset Alzheimer's disease, 19 with subcortical white matter dementia (SWD) and 28 normal controls underwent semiquantitative regional cerebral blood flow measurement (rCBF) using single-photon emission tomography (SPET; (99m)Tc-HMPAO) and either computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain. An anterior-to-posterior rCBF-SPET ratio (mesial superior frontal gyrus/medial temporal lobes) was calculated, which significantly separated the FTD group from the other dementia groups and controls with a sensitivity of 87.5% and a specificity of at least 78.6%. CT/MRI was found to be helpful in the differential diagnosis between FTD and SWD. In FTD patients, the mesial superior frontal gyrus, near the polus frontalis, was found to be the region with the most reduced rCBF values.

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PubMed2006

Caregiver burden, health-related quality of life and coping in dementia caregivers: a comparison of frontotemporal dementia and Alzheimer's disease.

Frontotemporal dementia (FTD) is the second most prevalent dementia after Alzheimer's disease (AD). We compared 29 FTD and 90 AD caregivers with respect to burden, health-related quality of life (HQoL) and coping. FTD caregivers were more burdened than AD caregivers, and caregivers of patients who were demented for shorter duration had lower HQoL. We furthermore compared the 29 FTD caregivers with 34 caregivers of institutionalized FTD patients to understand their specific caregiver issues. Caregivers of FTD patients institutionalized after shorter dementia duration were most burdened and affected in their HQoL. Overall, passive coping strategies were associated with increased burden and decreased HQoL. We recommend that FTD caregivers be offered more support than AD caregivers. Furthermore, we suggest that interventions target passive coping strategies.

Adaptation, Psychological↗
PubMedDate not supplied

Functional imaging of the frontal lobes in organic dementia. Regional cerebral blood flow findings in normals, in patients with frontotemporal dementia and in patients with Alzheimer's disease, performing a word fluency test.

Patterns of functional cortical activation were studied by means of regional cerebral blood flow measurements, performed during rest and during a word fluency task in normal subjects (n = 22), in patients with Alzheimer's disease (n = 17), and in patients with frontotemporal dementia (n = 15). Although all groups showed a significant activation of the Broca's area during word production, the activation of the dorsolateral prefrontal cortex was clearly subnormal in both dementia groups. The frontal dysfunction was not explained by number of words produced, illness duration, or age. Thus, the results demonstrate that the word fluency task is a sensitive measure of frontal lobe function, and its incorporation in imaging studies may facilitate the detection of subtle functional impairment of the frontal lobes in organic dementia.

Adult↗
PubMed1987

Multivariate analysis of Hachinski's Scale for discriminating senile dementia of the Alzheimer's Type from multiinfarct dementia.

The need for an accurate clinical scale to aid in the diagnosis of senile dementia of the Alzheimer's type (SDAT) is clear in terms of both patient care and research. The ischemic scale of Hachinski, which differentiates multiinfarct dementia from primary degenerative dementia, has been criticized as lacking in validity. This study is a cluster by case analysis of the data from Hachinski's original report. The multivariate analysis provides support for those clinicopathologic studies that have found Hachinski's ischemic score of value.

Alzheimer Disease↗
PubMed1992

Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree.

The cognitive and behavioral effects and the safety of oxiracetam therapy during a placebo-controlled trial and the relevant follow-up up to 1 year in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) of mild to moderate degree were studied. Sixty male and female outpatients participated in the double-blind, placebo-controlled, parallel-group, randomized trial, comparing the effects of oxiracetam 800 mg b.i.d. and placebo during 90 days of treatment. At the end of therapy, statistical analysis evidenced significant improvements in the group receiving oxiracetam in respect to the placebo group on Mini Mental State Examination, Auditory Continuous Performance Test, Rey's 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series and Instrumental Activities of Daily Living. Afterwards, 29 of the 30 patients who received oxiracetam, participated in the open follow-up study, receiving 800 mg b.i.d. oxiracetam for a total standard period of 1 year. Statistical improvements in comparison to baseline were again found on the same tests of the first 90 days (except for Rey's 15 Words Test) and on the Memory item of the Inventory of Psychic and Somatic Complaints Elderly. During the late phase of the follow-up, statistically significant worsenings in comparison to baseline were observed on Digit Span Backward, Gibson's Spiral and some non-memory items of IPSC-E. Neither severe adverse events were observed during the whole study, nor changes in routine laboratory examinations. In conclusion, in the present population of patients with mild to moderate degree dementia, the safety of 1,600 mg/day of oxiracetam also up to 1 year of treatment was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1993

Parkinson's dementia and Alzheimer's dementia: an evoked potential comparison.

Auditory endogenous event-related potentials (ERPs) and flash visual evoked potentials (VEPs) were recorded in 26 elderly patients with idiopathic Parkinson's disease (PD), 14 with dementia and 12 non-demented, 16 elderly patients with Alzheimer dementia (AD) and 15 cognitively intact controls. ERP P3 and flash-VEP N2, P2 and delta (P2-P1) latency measures were significantly increased in the demented PD group compared with controls. The ERP P3 latency was also significantly delayed in the AD group compared with controls, but the differences in the flash-VEP measures from controls were not significant. No significant differences were noted between the PD groups, except for a significantly shorter flash-VEP N1 latency in the demented PD group; this was also the only significant evoked potential difference between the AD and PD dementia groups, which were otherwise electrophysiologically similar.

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