Showing papers in "Journal of Neural Transmission-supplement in 1996"
TL;DR: The nosological status of FLD-MND remains enigmatic in the absence of defined pathological and molecular markers, whereas others suggest it represents an interface between FLD and "classic" (non-dementing) motor neuron disease (CMND).
Abstract: Frontal lobe dementia (FLD) (syn frontotemporal dementia and dementia of frontal type) is a generic term that describes a clinical syndrome in which patients manifest a profound breakdown in personality and social conduct, together with adynamic spontaneous speech, culminating in mutism This pattern of cognitive impairment implicates bilateral frontal lobe dysfunction, an assumption supported by functional neuroimaging findings of anterior cerebral abnormality Patients with FLD can go on to develop motor neuron disease (FLD-MND), although the clinical features of MND may accompany or occasionally precede the onset of dementia The emergence of MND is responsible for death within 3 years of onset Frontotemporal lobar pathology in FLD-MND is characterized by loss of large cortical neurons, spongiform change and mild astrocytic gliosis Ubiquitinated (but not tau-positive) inclusions are present within the frontal cortex There is severe nigral cell loss (without Lewy bodies), and marked hypoglossal and spinal motor neuron degeneration, together with ubiquitinated (but not tau-positive) inclusions within the spinal neurons Some authors suggest that FLD-MND is a separate disease entity, whereas others suggest it represents an interface between FLD and "classic" (non-dementing) motor neuron disease (CMND) An association with CMND is supported by findings in these patients of failure in tasks sensitive to "frontal lobe" dysfunction, and patterns of functional neuroimaging abnormality which are identical in distribution, but less severe than those encountered in FLD-MND However, the nosological status of FLD-MND remains enigmatic in the absence of defined pathological and molecular markers
222 citations
TL;DR: DFT and Alzheimer's disease can be separated with a high degree of certainty based on a combination of informant history, neuropsychology and neuroimaging, which reflects the major locus of pathology in AD, namely the medial temporal lobe.
Abstract: Over the past decade it has become evident that a substantial minority of patients with primary dementing diseases, particularly those presenting in the presenium, have dementia of frontal lobe type (DFT) due to non-Alzheimer’s pathology. Although post-mortem remains the only method of definitive diagnosis, DFT and Alzheimer’s disease (AD) can, we would claim, be separated with a high degree of certainty based on a combination of informant history, neuropsychology and neuroimaging.
114 citations
TL;DR: It is proposed that (-)-deprenyl acts on gene expression to maintain mitochondrial function and to decrease cytoplasmic oxidative radical levels and thereby to reduce apoptosis.
Abstract: (−)-Deprenyl stereospecifically reduces neuronal death even after neurons have sustained seemingly lethal damage at concentrations too small to cause monoamine oxidase-B (MAO-B) inhibition. (−)-Deprenyl can also influence the process growth of some glial and neuronal populations and can reduce the concentrations of oxidative radicals in damaged cells at concentrations too small to inhibit MAO. In accord with the earlier work of others, we showed that (−)-deprenyl alters the expression of a number mRNAs or proteins in nerve and glial cells and that the alterations in gene expression/protein synthesis are the result of a selective action on transcription. The alterations in gene expression/protein synthesis are accompanied by a decrease in DNA fragmentation characteristic of apoptosis and the death of responsive cells. The onco-proteins Bcl-2 and Bax and the scavenger proteins Cu/Zn superoxide dismutase (SODl) and Mn superoxide dismutase (SOD2) are among the 40–50 proteins whose synthesis is altered by (−)-deprenyl. Since mitochondrial ATP production depends on mitochondrial membrane potential (MMP) and mitochondrial failure has been shown to be one of the earliest events in apoptosis, we used confocal laser imaging techniques in living cells to show that the transcriptional changes induced by (−)-deprenyl are accompanied by a maintenance of mitochondrial membrane potential, a decrease in intramitochondrial calcium and a decrease in cytoplasmic oxidative radical levels. We therefore propose that (−)-deprenyl acts on gene expression to maintain mitochondrial function and to decrease cytoplasmic oxidative radical levels and thereby to reduce apoptosis. An understanding of the molecular steps by which (−)-deprenyl selectively alters transcription may contribute to the development of new therapies for neurodegenerative diseases.
89 citations
TL;DR: Rasagiline [R(+)-N-propargyl-1-aminoindane] is a selective irreversible inhibitor of MAO-B which is not metabolised to amphetamine-like derivatives and increased the number of neurons per field in this organotypic culture.
Abstract: Rasagiline [R(+)-N-propargyl-1-aminoindane] is a selective irreversible inhibitor of MAO-B which is not metabolised to amphetamine-like derivatives. Like deprenyl, when given to rats in a dose selective for inhibition of MAO-B, it does not affect striatal extracellular fluid dopamine levels, but when administered chronically (21 days) it increased striatal microdialysate dopamine without reduction in deaminated metabolites. Similarly to deprenyl, rasagiline (10-6M) increased the percentage of tyrosine hydroxylase positive cells in a primary culture of rat fetal mesencephalic cells (6 days in culture). Rasagiline, but not deprenyl, also increased the number of neurons per field in this organotypic culture.
86 citations
TL;DR: Biochemical studies have shown that Pick bodies, argyrophilic neuronal inclusions that are highly characteristic of, if not pathognomonic for PD are also composed of abnormal tau protein, and tau has recently been detected in glial cells in PD.
Abstract: Increasing use of immunocytochemistry for evaluation of dementia disorders has revealed histopathological alterations that were previously unknown, even with sensitive silver techniques. Disorders [Pick’s disease (PD), diffuse Lewy body disease (DLBD) and corticobasal degeneration (CBD)] in which immunocytochemistry has revealed occult pathology are discussed. All three disorders have neurofilament (NF) immunoreactive neuronal alterations in the neocortex. In DLBD round, eosinophilic cytoplasmic inclusions referred to as cortical Lewy bodies are neurofilament-positive, while in both PD and CBD neurofilament epitopes are expressed in irregularly swollen neurons and their proximal cell processes, which are referred to as ballooned neurons. Interestingly, the cortical neuronal population that is vulnerable to Lewy bodies is similar to that which is vulnerable to ballooned neurons. Furthermore, Lewy bodies can occasionally be detected within the cytoplasm of ballooned neurons. Besides neurofilament-immunoreactivity, Lewy bodies are immunoreactive for ubiquitin, while ballooned neurons are inconsistently stained with antibodies to ubiquitin. Both Lewy bodies and ballooned neurons can be appreciated with routine histology, but they are much easier to detect with immunocytochemistry. In contrast, a new type of neuritic alteration in the hippocampal CA2/3 region has been recognized in DLBD. These dystrophic neurites cannot be appreciated with routine histology and are only optimally seen with immunocytochemistry for ubiquitin. Their presence is a certain indication of the presence of cortical Lewy bodies.
64 citations
TL;DR: The expected increase in the Apolipoprotein epsilon 4 allele frequency is found and does not appear to influence the burden of AD type pathology and this is particularly relevant given the relative lack of NFT in LBD indicating that factors other than SP or NFT may govern the onset of dementia.
Abstract: Current research into the aetiology of the dementias is focused upon genetic factors which give rise to the disease process. Recently the Apolipoprotein E gene (APO E) and in particular the e4 allele has been shown to be a risk factor for late onset Alzheimer’s disease (AD) where there is an increased frequency of the e4 allele. The e4 allele has also been shown to reduce the age at onset of dementia in AD in a dose dependant manner, with the e2 allele having an opposing effect.
50 citations
TL;DR: While in Alzheimer’s disease (AD) mental decline is mainly related to synaptic and neuritic pathologies, other degenerative disorders show variable substrates of dementia involving different cortical and/or subcortical circuits which may or may not be superimposed by cortical Alzheimer lesions.
Abstract: Progressive dementia syndromes in adults are caused by a number of conditions associated with different structural lesions of the brain. In most clinical and autopsy series, senile dementia of the Alzheimer type is the most common cause of mental decline in the elderly accounting for up to 90%, whereas degenerative non-Alzheimer dementias range from 7 to 30% (mean 8–10%). They include a variety of disorders featured morphologically by neuron and synapse loss and gliosis, often associated with cytopathological changes involving specific cortical and subcortical circuits. These neuronal/ glial inclusions and neuritic alterations show characteristic immunoreactions and ultrastructure indicating cytoskeletal mismetabolism. They are important diagnostic sign posts that, in addition to the distribution pattern of degenerative changes, indicate specific vulnerability of neuronal populations, but their pathogenic role and contribution to mental decline are still poorely understood. In some degenerative disorders no such cytopathological hallmarks have been observed; a small number is genetically determined. While in Alzheimer’s disease (AD) mental decline is mainly related to synaptic and neuritic pathologies, other degenerative disorders show variable substrates of dementia involving different cortical and/or subcortical circuits which may or may not be superimposed by cortical Alzheimer lesions. In most demented patients with Lewy body disorders (Parkinson’s disease, Lewy body dementia), they show similar distribution as in AD, while in Progressive Supranuclear Palsy (PSP), mainly prefrontal areas are involved. Lobar atrophies, increasingly apparent as causes of dementia, show fronto-temporal cortical neuron loss, spongiosis and gliosis with or without neuronal inclusions (Pick bodies) and ballooned cells, while dementing motor neuron disease and multisystem atrophies reveal ubiquitinated neuronal and oligodendroglial inclusions. There are overlaps or suggested relationships between some neurodegenerative disorders, e.g. between corticobasal degeneration, PSP and Pick’s atrophy. In many of these disorders with involvement of the basal ganglia, degeneration of striatofrontal and hippocampo-cortical loops are important factors of mental decline which may be associated with isocortical neuronal degeneration and synapse loss or are superimposed by cortical AD pathology.
46 citations
TL;DR: There is evidence that l-amphetamine and l-methamphetamine have some qualitatively different actions than their d-isomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.
Abstract: A frequent topic of controversy has been whether metabolism of l-deprenyl (selegiline) to active metabolites is a detriment to clinical use. This paper reviews possible roles of the metabolites of l-deprenyl in producing unwanted adverse side effects or in augmenting or mediating its clinically useful actions. Levels of l-amphctamine and l-methamphetamine likely to be reached, even with excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In contrast, there is evidence that l-amphetamine and l-methamphetamine have some qualitatively different actions than their disomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.
44 citations
TL;DR: A meta-analysis of neurochemical changes in human post mortem brains of Alzheimer type (AD), vascular type (VD) and mixed type (MF) dementias, and matched controls based on 275 articles published between January 1980 and February 1994 finds that degeneration within a neurochemical system is not evenly distributed.
Abstract: We present the results of a meta-analysis of neurochemical changes in human post mortem brains of Alzheimer type (AD), vascular type (VD) and mixed type (MF) dementias, and matched controls based on 275 articles published between January 1980 and February 1994.
42 citations
TL;DR: The most widely used MAO-B inhibitor in the therapy is (−)-deprenyl and it lacks the "cheese reaction" as discussed by the authors, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells.
Abstract: (−)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous system by a complex mechanism. The MAO-B inhibition could result in a potentiation of the effect and the reduction of the dose of L-dopa, including the restoration of the sensitivity to L-dopa treatment, when the response to the drug has already been diminished or lost. Pre-treatment with (−)deprenyl prevent the effect of neurotoxins like MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the combination of the two processes. However, other effects of the inhibitor cannot be ruled out. (−)-deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic agents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (−)-deprenyl and it lacks the “cheese reaction”. The complex mechanism for the lack of the former effect is not fully known.
40 citations
TL;DR: Toxic effects of acute glutamate exposure were prevented by Cerebrolysin in a concentration-dependent manner and were evident even at the light microscopic level.
Abstract: Glutamate induced neurotoxicity has been proposed to account for the loss of neurons after ischemia as well as in the cause of neurodegenerative diseases. We have studied the effects of exogenous glutamate on survival of neurons from chick embryo telencephalon, precultured with a peptide derivative for 8 days. The peptide derivative Cerebrolysin® is a drug produced by standardised enzymatic breakdown consisting of 80% peptides and 20% amino acids. Toxic effects of acute glutamate exposure were prevented by Cerebrolysin in a concentration-dependent manner. 20 and 40µl Cerebrolysin produce distinct neuroprotective effects. However, 80µ1 Cerebrolysin/ml nutrition medium more than doubles neuronal viability compared to untreated control cells. These concentration-dependent effects of Cerebrolysin were evident even at the light microscopic level.
TL;DR: Presently available data support the view that fully developed Parkinson's disease with concurring incipient Alzheimer's disease is likely to cause impaired cognition.
Abstract: Alzheimer’s disease and Parkinson’s disease are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In Alzheimer’s disease, susceptible neurons produce neurofibrillary tangles and neuropil threads, while in Parkinson’s disease, they develop Lewy bodies and Lewy neurites. The specific lesional pattern of both illnesses accrues slowly over time. Presently available data support the view that fully developed Parkinson’s disease with concurring incipient Alzheimer’s disease is likely to cause impaired cognition.
TL;DR: It is concluded that priming with serum is important to make DAergic neurons fully responsive to BDNF and NT-4 and underlying mechanisms might be sought at the level or distal of trkB receptor expression, without excluding the possiblity that serum elicits production of growth factors that synergistically act with neurotrophins in these cultures.
Abstract: The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are established survival promoting molecules for dopaminergic (DAergic) neurons cultured from the fetal rat midbrain floor. We have cultured and compared the survival of embryonic day (E) 14 mesencephalic cells in fully defined, serum-free medium, with serum-primed cultures (one hour during dissociation). Cultures were characterized using antibodies against neuron-specific enolase (NSE), tyrosine hydroxylase (TH), vimentin, glial fibrillary acidic protein (GFAP), and the antigen A2B5. The absolute absence of serum did not reduce the survival of TH-positive DAergic neurons nor alter the percentages of cells staining for the above markers. Transforming growth factor-β3 (TGF-β3) and glial cell line-derived neurotrophic factor (GDNF), two members of the TGF-β superfamily, both promoted the survival of TH-positive cells (TGF-β3: 2-fold; GDNF: 1.6-fold) over the 8-day culture period. Survival mediated by TGF-β3 and GDNF was independent of whether or not the cells had been initially exposed to serum. In contrast, the survival promoting effects of BDNF and NT-4 were crucially dependent on serum priming. RT-PCR for the full-length trkB high affinity neurotrophin receptor revealed its presence in both culture systems. We conclude that priming with serum is important to make DAergic neurons fully responsive to BDNF and NT-4. Underlying mechanisms might be sought at the level or distal of trkB receptor expression, without excluding the possiblity that serum elicits production of growth factors that synergistically act with neurotrophins in these cultures.
TL;DR: Recent studies suggest that neuroprotection in laboratory models may be related to the capacity of selegiline to up-regulate a series of anti-oxidant and anti-apoptotic molecules which promote cell survival.
Abstract: Selegiline is a relatively selective inhibitor of monoamine oxidase type B that has been used in Parkinson’s disease as an adjunct to levodopa and as putative neuroprotective therapy. Clinical trials demonstrate that selegiline slows the rate of disease progression and delays the appearance of disability necessitating levodopa. However, confounding symptomatic effects have made it difficult to ascertain the presence of any direct neuroprotective effect. Laboratory studies demonstrate that selegiline protects dopaminergic neurons through a mechanism that does not involve MAO-B inhibition. Recent studies suggest that neuroprotection in laboratory models may be related to the capacity of selegiline to up-regulate a series of anti-oxidant and antiapoptotic molecules which promote cell survival. Further delineation of the precise mechanism whereby selegiline induces this effect may permit for the development of enhanced neuroprotective benefits in PD patients.
TL;DR: There was greater electrophysiological resemblance between the control group and FLD than between any of these groups and Alzheimer's disease, and this was documented by the results of a discriminant analysis.
Abstract: A study on quantitative EEG in 14 patients with frontal lobe dementia (FLD), 14 patients with Alzheimer’s disease (AD), and 14 healthy controls was conducted using a complete set of EEG parameters: band power, coherence and fractal dimension Contrary to earlier studies, we observed higher theta power and sagittal interactions in higher frequency bands in the FLD than in the control group Lateral interactions of coherence and two indices of fractal dimension were lower in FLD than in controls There was greater electrophysiological resemblance between the control group and FLD than between any of these groups and AD This was documented by the results of a discriminant analysis which led to a correct overall classification of 66% of the subjects with misclassifications occurring primarily between control and FLD group
TL;DR: Most patients referred to as DPD, suffer from depression-induced cognitive symptoms outside the range of dementia, but complain of memory disturbance and inability to think or concentrate.
Abstract: Depressive disorder causes cognitive symptoms. In the case of severe cognitive symptoms or when psychometric procedures measure cognitive decline in the range of dementia, depressed patients may be diagnosed as Depressive Pseudo-Dementia (DPD). There is no data that depressive disorder can cause dementia without coexisting depressive symptoms. The latter symptoms are frequently overseen because cognitive symptoms are equated with organic brain disease. There are typical neuropsychological features of cognitive decline in depressive disorders, like psychomotor retardation and the slow-start phenomenon.
TL;DR: A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.
Abstract: Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.
TL;DR: The concept that excitotoxicity is linked with the generation of free radicals is considered and how selegiline might exert its neuroprotective effects via indirect actions on the polyamine binding site of the NMDA receptor is discussed.
Abstract: There have been many claims that the selective monoamine oxidase type B (MAO-B) inhibitor selegiline may have distinct properties in slowing the progression of Parkinson's disease (PD). Degeneration of nigro-striatal dopaminergic neurons is the primary histopathological feature of PD. Although many different hypotheses have been advanced, the cause of chronic nigral cell death and the underlying mechanisms remain elusive as yet. Therefore, there is no clear knowledge regarding an understanding of the reported effects of selegiline on the progression of PD. However, there is a considerable body of indirect evidence that oxidative stress may play a role in the pathogenesis of this illness. Oxidative stress refers to cytotoxic consequences of hydrogen peroxide and oxygen-derived free radicals such as the hydroxyl radical (.OH), the superoxide anion (.O2), and nitric oxide (NO), which are generated as byproducts of normal and aberrant metabolic processes that utilize molecular oxygen. On the other hand, an increasing body of experimental data has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurological disease. One of the receptor which is particularly involved in the toxic effects of excitatory amino acids is the NMDA (N-methyl-D-aspartate) receptor. Excessive stimulation of this type of receptor by glutamic acid or NMDA agonists leads to a massive influx of calcium ions into the neuron followed by activation of a variety of calcium-dependent enzymes, impaired mitochondrial function, and the generation of free radicals. This article will consider the concept that excitotoxicity is linked with the generation of free radicals. In view of this idea it will be further discussed how selegiline might exert its neuroprotective effects via indirect actions on the polyamine binding site of the NMDA receptor. Under treatment with the MAO-B inhibitor selegiline, the degradation of putrescine via MAO, a key factor in regulating the polyamine metabolism, might be diminished in the Parkinsonian brain, which in turn would suppress the polyamine synthesis. Hence, the reported neuroprotective effect of selegiline might also receive a contribution from the diminished potentiation of the NMDA receptor by the polyamine binding site. On the other hand, since N1-acetylated spermine and spermidine are also good substrates of MAO-B, it is likely that these compounds will be present in the brain in increased concentrations. It therefore seems possible that they will exert a neuroprotective effect via an antagonistic modulation of the polyamine binding site of the NMDA receptor.
TL;DR: Microtubule — associated protein 2 (MAP2) was studied in cultured neurons from chick embryo hemispheres after neuronal damage caused by cytotoxic ischemia in a medium supplemented with Cerebrolysin® in the appropriate concentration.
Abstract: Microtubule — associated protein 2 (MAP2) was studied in cultured neurons from chick embryo hemispheres after neuronal damage caused by cytotoxic ischemia. Cortical cells were pretreated with 0, 10, 20, 40 or 80µ1 Cerebrolysin® per ml media. After 8 days in vitro (DIV), ischemia was induced by a 60 minutes incubation with 1 mM L-glutamate. After this toxic stress, cells were allowed to recover from ischemia for 48 hours in a medium again supplemented with Cerebrolysin® in the appropriate concentration. For immunoblot analysis cortical cells were lysed in 1% SDS and the supernatants were assayed for protein content by the method of Lowry. Proteins were then separated and transferred to nitrocellulose (0.5 A for 2h). Western blots were blocked with low fat milk and incubated with the primary monoclonal antibody (Chemicon) reacting with all forms of MAP2 (Map2a, Map2b, Map2c) for 12–14 hours at 4°C. Incubation with the horseradish peroxidase — conjugated secondary antibody lasted for 2h. For detection we used a nonradioactive ECL (enhanced chemiluminescence) system (Amersham).
TL;DR: The identification of an apparently new variant of CJD in young patients in UK raises the possibility of such a link; further studies are required to assess the significance of this observation.
Abstract: The classical prion diseases in man comprise Creutzfeldt-Jakob disease (CJD), Kuru and Gerstmann-Straussler-Scheinker syndrome (GSS). Recent advances in the biochemistry and the molecular biology of the transmissible agents responsible for these human spongiform encephalopathies have prompted renewed interest in their clinical and pathological features. A broadening spectrum of human prion diseases has now been identified including novel entities such as Fatal Familial Insomnia and variants of CJD and GSS characterised by specific abnormalities in the human prion protein (PrP) gene on chromosome 20. Accumulation of PrP in the central nervous system is a characteristic feature of all these disorders, although the relationship between PrP localisation, classical neuropathology, clinical features and genotype still requires clarification. A national surveillance project for CJD was established in 1990 in the United Kingdom in order to assess the possible implications of bovine spongiform encephalopathy for human health. The identification of an apparently new variant of CJD in young patients in UK raises the possibility of such a link; further studies are required to assess the significance of this observation.
TL;DR: Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of dementia and prominent symptoms and signs of the frontal type; a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions.
Abstract: Ten successive cases from the Neuropathology Laboratory of La Salpetriere Hospital in Paris, were selected on the presence of:
dementia and prominent symptoms and signs of the frontal type;
a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions.
We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type:
1.
If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease.
2.
If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II–III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers.
3.
When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.
TL;DR: Neurotrophic factors of dopaminergic neurons may represent a potential neuroprotective therapy for PD and its possible future clinical relevance is discussed.
Abstract: Neurotrophic factors of dopaminergic neurons may represent a potential neuroprotective therapy for PD. This article reviews published experiments that demonstrate the effects of neurotrophic factors on dopaminergic neurons in vitro and in vivo. At present this issue is predominantly investigated in basic neuroscientific research. Its possible future clinical relevance is discussed.
TL;DR: The results of clinical studies with Deprenyl in various neurologic and psychiatric disorders except Parkinson's disease are reviewed, finding that for depression a higher dosage of deprenyl between 30 to 60 mg/day appears to be necessary for effective treatment.
Abstract: This article reviews the results of clinical studies with Deprenyl in various neurologic and psychiatric disorders except Parkinson’s disease. Promising results could be observed both in narcolepsy in a dose of at least 20 mg/day in three different trials and in one study of Tourette’s syndrome including attention hyperactivity disorders using an average dosis of 8.1 mg/ day. Controversial results were reported for Alzheimer’s disease. On the one hand significant improvement of cognitive functions was found by various authors. On the other hand in a more recent study no effect on the progression of the disease could be observed. For depression a higher dosage of deprenyl between 30 to 60 mg/day appears to be necessary for effective treatment. No positive results were found in amyotrophic lateral sclerosis and in tardive dyskinesias.
TL;DR: Findings contribute to the differential diagnosis of these disorders by showing a different neurobiochemical CSF profile and possibly will further increase the value of CSF investigation in neurodegenerative disorders.
Abstract: Tau protein and apolipoprotein E are suggested to be biochemically related to neurofibrillary tangles and senile plaques in Alzheimer’s disease (AD) brains. They can be detected as immunoreactive material (total tau immunoreactivity [TTIR] and apolipoprotein E-immunoreactivity [ApoEIR]) in the cerebrospinal fluid (CSF).
TL;DR: Nerve Growth Factor and Cerebrolysin® (Cer) can support the function of neurons affected by unilateral fimbria-fornix lesion in short term experiment, while no short-term influence of Fibroblast Growth Factor (FGF) was found.
Abstract: Nerve Growth Factor (NGF) and Cerebrolysin® (Cer) can support the function of neurons affected by unilateral fimbria-fornix lesion in short term experiment, while no short-term influence of Fibroblast Growth Factor (FGF) was found.
TL;DR: The degree of overlap justifies the concept of "Pick complex" to include, in addition to the above, corticobasal ganglionic degeneration and some instances motor neuron disease with dementia.
Abstract: The recently described conditions of primary progressive aphasia and frontal lobe dementia overlap clinically and pathologically to a considerable extent with each other and with clinical and pathological descriptions of Pick’s disease. Our clinical and neuropathological experience is summarized, leading us to the conclusion that the degree of overlap justifies the concept of “Pick complex” to include, in addition to the above, corticobasal ganglionic degeneration and some instances motor neuron disease with dementia.
TL;DR: The bulk of the research on non-Alzheimer dementias has been performed with PET and SPECT and this review will concentrate on these two modalities.
Abstract: Functional imaging (positron emission tomography — PET, single photon emission tomography — SPECT, magnetic resonance spectroscopy — MRS) enables regional cerebral function to be assessed in vivo in dementias. There are three basic approaches to examining the patterns of cerebral function associated with specific disorders: First, abnormalities in resting levels of regional cerebral metabolism and blood flow can be examined. Second, patients can be asked to perform cognitive tasks with a view to demonstrating aberrations in their pattern of cerebral activation. Third, resting dysfunction of brain pharmacology can be revealed. The bulk of the research on non-Alzheimer dementias has been performed with PET and SPECT and this review will concentrate on these two modalities.
TL;DR: The multimodality of MR represents a diagnostic challenge for the future with the hope, that the diagnostic efficacy, which has to be proven, is also followed by an improvement of patients care and prognosis.
Abstract: Up to now, computerized tomography (CT) and MR-imaging have been used for the morphological assessment of dementia patients, while MRI has become the structure imaging modality of choice. With the advent of fast and ultrafast sequences provided by higher gradient field strenghts, functional MR studies like diffusion, perfusion and activation studies become available
TL;DR: Together with other tools, such as the neurological examination or the functional imagery, the neuropsychological exam may contribute to characterize the clinical picture of a patient with non-Alzheimer's degenerative disease and therefore to determine a clinical diagnosis that remains probable till the neuropathological confrontation.
Abstract: Although observed in various brain disorders, dementia is particularly frequent in neurodegenerative diseases. Alzheimer’s disease is characterized by the association of progressive amnesia with either instrumental (aphasia, apraxia, agnosia) or behavioral (apathy, indifference, anosognosia) disorders, depending upon the location of the underlying neuronal lesions. By contrast, memory, linguistic, praxic, visuo-spatial or comportemental impairments are dissociated in more focal “lobar” atrophies, while planning and retrieval deficits predominate in movement disorders with dementia. Alzheimer’s and non-Alzheimer’s neurodegenerative diseases can therefore be distinguished insofar as the severity and location of the associated neuronal lesions differ.
TL;DR: In an attempt to compare the effect of b-FGF, NGF and the nootropic drug Cerebrolysin® (Cer) (EBEWE Arzneimittel), naive 3-month-old rats were trained to escape from water in the Morris pool to a hidden platform and tested for their ability to remember the position of the platform.
Abstract: Neurotrophic factors were shown to prevent degeneration and to facilitate regeneration in damaged CNS. In an attempt to compare the effect of b-FGF, NGF and the nootropic drug Cerebrolysin® (Cer) (EBEWE Arzneimittel), naive 3-month-old rats (Long Evans strain) were trained to escape from water in the Morris pool to a hidden platform (3 consecutive days; D1, D2, D3; 8 trials/day). Next day, fimbria-fornix (FF) was unilaterally removed by suction. A needle connected to a micro-osmotic pump filled by b-FGF (0.2μg/ml) or NGF (11μg/m1 or 0.5μg/) was placed into the lateral ventricle ipsilateral to the lesion., Cer was applied via intraperitoneal injection (2.5m1/kg/day). One group was treated by Cer and NGF (11μg/m1)(group NGFCER). As control groups served intact (INT) and lesioned only rats (LES). After the 14-daytreatment (D19) rats were tested for their ability to remember the position of the platform. During the next 3 days (D20, D21, D22) rats were trained to find the platform placed in a opposite quadrant of the pool. The length of trajectory and escape latency were recorded and speed of swimming was calculated.