Coma in a patient with Alzheimer's disease taking low dose trazodone and gingko biloba.
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Biomedical subjects
Publications and source records attributed to M Trabucchi.
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OBJECTIVE: To test the hypothesis that delusions are associated with asymmetric involvement of the temporal lobe regions in Alzheimer's disease. METHODS: Temporal lobe atrophy was assessed with a linear measure of width of the temporal horn (WTH) taken from CT films. Temporal asymmetry was computed as the right/left (R/L) ratio of the WTH in 22 non-delusional and 19 delusional patients with Alzheimer's disease. Delusional patients had paranoid delusions (of theft, jealousy, persecution). None of the patients had misidentifications or other delusions of non-paranoid content. RESULTS: The R/L ratio indicated symmetric temporal horn size in the non-delusional (mean 1. 05 (SD 0.20), and right greater than left temporal horn in the delusional patients (mean 1.30, (SD 0.46); t=2.27, df=39, p=0.03). When patients were stratified into three groups according to the R/L ratio, 47% of the delusional (9/19) and 14% of the non-delusional patients (3/21; chi(2)=5.6, df=1, p=0.02) showed right markedly greater than left WTH. CONCLUSIONS: Predominantly right involvement of the medial temporal lobe might be a determinant of paranoid delusions in the mild stages of Alzheimer's disease.
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The localization of vasoactive intestinal peptide (VIP)-like immunoreactive (ir) elements was investigated in the brain of the anuran amphibian, Rana esculenta, during development. Using an antiserum raised against the porcine VIP, ir cell bodies and fibers were observed in the forebrain of tadpoles a few days after hatching. During early premetamorphosis, ir perikarya were distributed in the ventral infundibular nucleus of the hypothalamus and in the posterocentral nucleus of the thalamus. Labeled fibers were detected in the olfactory bulbs and in the hypothalamus. In these larvae, furthermore, several VIP-ir cells were found in the pars distalis of the pituitary and there were ir fibers in the pars nervosa. In tadpoles at stages VIII-IX, a new group of VIP-labeled neurons was observed in the dorsal part of the infundibular nucleus. In other brain regions, the distribution of the immunoreactivity was similar to that described in the earliest stages, i.e., IV-VII. During mid-premetamorphosis, stages X-XII of development, an additional set of ir perikarya appeared in the ventrolateral area of the thalamus. During late premetamorphosis, stages XIII-XVIII, the organization of VIP-like immunoreactivity was more complex and its distribution more widespread. Two new groups of ir cell bodies appeared, one in the preoptic nucleus and another in the anteroventral area of the thalamus, and for the first time, VIP immunoreactivity was observed in the median eminence. This distribution pattern persisted through to the prometamorphic, four-limb stage. Strikingly, no VIP-ir elements were observed anywhere in the mid- and hindbrain. The present results indicate that a VIP-like ir peptide may be involved in the processing of olfactory information or may act as a neurohormone, hypophysiotropic factor, and neuromodulator in the brain of R. esculenta during development.
Alcohol administration (1 g/kg, i.p.) increased the levels of the neurosteroids 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THDOC) in the cerebral cortex and hippocampus both in alcohol-naive Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats (two rat lines selectively bred for alcohol preference and non-preference, respectively). However, the increase reached several fold higher levels in sP than in sNP rats (6-24 vs. 2-11 fold the basal levels, respectively). Since the two neurosteroids are the most potent endogenous positive modulators of GABA(A) receptors and elicit anxiolytic and rewarding effects, while voluntary alcohol consumption produces anxiolytic and rewarding effects in sP but not in sNP rats, the results suggest that the neurosteroids may play a role in the anxiolytic and rewarding effects of alcohol in sP rats.
OBJECTIVE: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. RESULTS: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03). CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.
Presenilin proteins are involved in familial Alzheimer's disease, a neurodegenerative disorder characterized by massive death of neurons. We describe a direct interaction between presenilin 1 (PS1) and Bcl-2, a key factor in the regulation of apoptosis, by yeast two-hybrid interaction system, by co-immunoprecipitation, and by cross-linking experiments. Our data show that PS1 and Bcl-2 assemble into a macromolecular complex, and that they are released from this complex in response to an apoptotic stimulus induced by staurosporine. The results support the idea of cross-talk between these two proteins during apoptosis.
The occurrence of two somatostatin precursors, PSS1 and PSS2, yielding S-14 (SS1) and the variant [Pro2, Met13]S-14 (SS2), has been recently reported in the frog Rana ridibunda. The evolutionary significance of frog PSS2 is unclear because its sequence exhibits very little similarity with other known vertebrate somatostatin precursors. In the present study, we report on the characterization of two somatostatin precursor cDNAs from the brain of the African lungfish Protopterus annectens. One of the cDNAs encodes a 115-amino-acid protein that contains the SS1 sequence at its C-terminal extremity and thus is clearly homologous to PSS1. Comparison with other vertebrate PSS1 showed that lungfish PSS1 is more closely related to PSS1 from tetrapods than to PSS1 from fish. The other cDNA encodes a 109-amino-acid protein that contains a somatostatin variant [Pro2]S-14 at its C-terminal extremity. Sequence analysis of this second precursor indicated that it is the lungfish counterpart of frog PSS2. Northern blot analysis showed that lungfish PSS1 mRNA is widely distributed in the central nervous system and in peripheral organs, including the pancreas and gastrointestinal tract. In contrast, PSS2 mRNA was primarily found in the central nervous system but not in the pancreas or gut. In situ hybridization studies showed that the two genes are differentially expressed in various regions of the lungfish brain. The present data indicate that the PSS2 gene, initially discovered in frog, appeared early in vertebrate evolution, before the emergence of the tetrapod lineage. The recent isolation of a [Pro2]S-14 variant in the sturgeon, whose sequence is identical to that of lungfish SS2, suggests that the PSS2 gene may actually be present in the genome of all Osteichthyii.
The present study investigates the influence of aglycemia and sodium azide (a Cytochrome c Oxidase inhibitor) on sAPP secretion from skin fibroblasts derived from sporadic AD patients and control subjects. Aglycemia reduced sAPP release in the medium of both AD and control fibroblasts to a similar extent after 2 h incubation. Treatment for 2 h with increasing azide concentrations (1 microM-100 mM) under glucose deprivation did not significantly affect sAPP secretion from control fibroblasts, but was able to significantly inhibit sAPP secretion from AD fibroblasts (maximal inhibition 51%). The failure of antioxidants like glutathione (GSH) or N-acetylcysteine (NAC) to antagonize the azide effect on AD fibroblasts and lipoperoxidation data seemed to rule out the possibility that oxidative stress could mediate the sodium azide effect on sAPP release from AD fibroblasts.
The positive efficacy of estrogen replacement therapy (ERT) in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) is a matter of intense debate among clinicians and neuroscientists. The experimental and preliminary clinical evidence supporting the use of ERT are based on epidemiological data and on the study of the effect of estrogens on several aspects of brain homeostasis, including the modulation of neurotransmitters and vascular changes. In spite of numerous data available the mechanisms underlying the putative estrogen effects in neurodegenerative diseases are largely unknown. The aim of this paper is to discuss and elaborate on some of the hypotheses and controversial findings currently present in this field.
OBJECTIVE: To describe atrophic changes of the hippocampus and entorhinal cortex in frontotemporal dementia (FTD) and compare them with those of AD. BACKGROUND: The medial temporal lobe shows atrophic changes early in the course of AD, but whether these changes are specific to AD or occur in other degenerative dementias, and to what extent, is unclear. METHODS: The authors measured the volumes of the left and right hippocampus and entorhinal cortex from MR images (1.5 T, 2-mm-thick slices) in 12 patients with FTD, 30 with AD, and 30 elderly control subjects. RESULTS: In FTD patients, the left and right hippocampus (16% and 21% tissue loss) and the entorhinal cortex (28% and 27% loss) were more atrophic than the control subjects. Atrophy of the hippocampus in FTD was less severe than in AD, but atrophy of the entorhinal cortex was equally severe. Greater hippocampal and entorhinal cortex atrophy was present in the most severe patients in both groups (as high as a 49% tissue loss). The sensitivity of the hippocampus and the entorhinal cortex to discriminate FTD patients from control subjects was low (49% and 52%, respectively; specificity set at 90%), whereas hippocampal volumes could better differentiate AD patients from control subjects (80% sensitivity). CONCLUSIONS: At variance with AD, detectable in vivo atrophy of the hippocampus might not be an early event in FTD. Differential patterns of atrophy might help in the diagnostic process of the degenerative dementias.
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In the present study we have investigated the localization and biochemical characteristics of urotensin I (UI)-like and urotensin II (UII)-like immunoreactive peptides in the central nervous system (CNS) and pituitary of the lungfish, Protopterus annectens, by using antisera raised against UI from the white sucker Catostomus commersoni and against UII from the goby Gillichythys mirabilis. UI-like immunoreactive material was found within the melanotrope cells of the intermediate lobe of the pituitary. By contrast, no UI-immunoreactive structures were found in the brain. No UII-like peptides structurally similar to goby UII were found in the brain and pituitary of P. annectens. The UI-immunoreactive material localized in the pituitary was characterized by combining reversed-phase high-performance liquid chromatography (HPLC) analysis and radioimmunological detection. The UI-like immunoreactivity contained in a pituitary extract eluted as a single peak with a retention time intermediate between those of sucker UI and rat corticotropin-releasing factor (CRF). Control tests on adjacent sections of pituitary showed that the UI antiserum cross-reacted with the frog skin peptide sauvagine, but lungfish UI did not co-elute with synthetic sauvagine on HPLC. On the contrary, no cross-reaction was observed between the UI antiserum and CRF or alpha-melanocyte-stimulating hormone (alpha-MSH). The occurrence of an UI-like peptide in the intermediate lobe of the pituitary of P. annectens suggests that, in lungfish, this peptide may act as a classic pituitary hormone or may be involved in the control of melanotrope cell secretion.
Elderly people frequently complain of somatic (physical) symptoms that prompt them to seek medical intervention. The aim of this study was to evaluate the effect of cognitive impairment on somatic symptom complaints by the elderly. Symptoms (spontaneously reported and reported after explicit inquiry) pertaining to 15 organ systems were assessed in a random sample of 462 community-dwelling individuals over the age of 75 years. The symptoms increased with decreasing cognitive performance with no, very mild, and mild cognitive impairments as indicated on the Mini-Mental State Examination. The trend of increasing reports of symptom with decreasing cognitive performance was significant (p = .0001); the association remained significant after controlling for potential confounders in multivariate analysis (p < .05). The authors, who found that mild cognitive impairment was associated with perception of poorer body functioning, suggest that the clinical interpretation of somatic symptoms in the elderly should take cognitive impairment into account.
PRESENTATION: A 76-year-old woman, complaining of leg pain and unsteady gait for 3 years, presented with a spastic paraparetic gait, severe spasticity and touch, thermal and pain sensory loss limited to arms, lower thorax and upper abdomen. Brain and spinal cord magnetic resonance imaging showed a large loculated syrinx. Cerebellar tonsillar herniation into the foramen magnum was also seen (Arnold-Chiari malformation, type I). OUTCOME: The patient had successful cervico-spinal surgical decompression which resulted in marked reduction in hypertonia and weakness, normal gait and normal joint movement at 6 months. CONCLUSION: This unusual, late clinical presentation of a congenital disease underlines the importance of a comprehensive diagnostic work-up in the elderly patients with complex neurological signs.
Lack of insight or impaired awareness of deficits in patients with dementia is a relatively neglected area of study. The aim of this study was to evaluate insight in a group of demented patients with two assessment scales and to assess their relationship with the cognitive level of disease severity. Sixty-nine consecutive patients affected by Alzheimer's disease (n = 37) and vascular dementia (n = 32) with a wide range of cognitive impairment (MMSE = 17.0 +/- 6.4) were recruited. Insight was evaluated with the Guidelines for the Rating of Awareness Deficits (GRAD)--specifically targeted to memory deficits--and the Clinical Insight Rating scale (CIR), evaluating a broader spectrum of insight (reason for the visit, cognitive deficits, functional deficits, and perception of the progression of the disease). In the whole sample, GRAD and CIR were significantly associated with MMSE (Spearman's coefficient = .51, p < .001; and r = -.55, p < .001) and with Clinical Dementia Rating scale (-.57, p < .001; and r = .57, p < .001) respectively. The shape of the relationship of MMSE with CIR and GRAD scales was assessed with spline smoothers suggesting that the relationship follows a trilinear pattern and is similar for both scales. Insight was uniformly high for MMSE scores > or = 24, showed a linear decrease between MMSE scores of 23 and 13, and was uniformly low for MMSE scores < or = 12. The trilinear model of the association between insight and cognitive status reflects more closely the observable decline of insight and can provide estimates of when the decline of insight begins and ends.
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