Biomedical subjects

F Lucchelli

Publications and source records attributed to F Lucchelli.

17 recordsLinked to original sources

PubMed1999

Efficacy and safety of eptastigmine for the treatment of patients with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy and safety of eptastigmine in patients with moderate to moderately severe AD. BACKGROUND: Eptastigmine is a centrally acting cholinesterase inhibitor. METHODS: The study was carried out according a multicenter, randomized, double-blinded, placebo-controlled, parallel-group design. Patients received a 24-week treatment with placebo or eptastigmine 15 mg or 20 mg three times daily after a 4-week, stepwise dose escalation. The effects of treatment on cognition, global function, and activities of daily living were evaluated with the Alzheimer's Disease Assessment Cognitive Subscale (ADAS-Cog), the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus), and the Instrumental Activities of Daily Living scale (IADL), respectively. RESULTS: Thirty-six centers recruited 491 patients: 164 on placebo, 166 on eptastigmine 15 mg three times daily, and 161 on eptastigmine 20 mg three times daily. Percentages of patients completing double-blinded treatment were 87% in the placebo group and 86% in both the eptastigmine-treated groups. At the end of treatment, the intent-to-treat analysis on 463 patients showed a dose-dependent effect of eptastigmine on all efficacy variables, with a statistically significant effect of the 20 mg three times daily dose compared with placebo on the ADAS-Cog, CIBIC-Plus, and IADL. Patients on eptastigmine 15 mg three times daily performed significantly better than placebo-treated patients only on the ADAS-Cog. Eleven patients on placebo (7%), 13 patients on eptastigmine 15 mg three times daily (8%), and 12 patients on eptastigmine 20 mg three times daily (8%) discontinued study treatment because of adverse events. Adverse events were recorded in 49% of patients on placebo compared with 54% on eptastigmine 15 mg three times daily and 48% on eptastigmine 20 mg three times daily. Cholinergic side effects (nausea, vomiting, diarrhea, and abdominal pain) were reported with similar frequency in the eptastigmine- and placebo-treated patients. There was a dose-dependent transient and mild neutropenic effect associated with eptastigmine treatment, and one patient on 20 mg three times daily had an asymptomatic pancytopenia. CONCLUSIONS: Eptastigmine produces significant cognitive, clinical, and functional benefits in patients with probable AD. Although the cholinergic tolerability of eptastigmine was found to be favorable, its potential adverse hematologic effects limit its clinical utility.

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PubMed1998

A 25-week placebo-controlled study of eptastigmine in patients with Alzheimer disease.

The efficacy and safety of eptastigmine in patients with probable Alzheimer disease was evaluated in a double-blind, placebo-controlled, parallel group study. Patients with mild to moderate dementia were randomly assigned to placebo, eptastigmine 10 mg three times a day (t.i.d.), or eptastigmine 15 mg t.i.d. over 25 weeks. The Alzheimer Disease Assessment Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus) were the primary outcome measures for efficacy. Twenty-six centers recruited 320 patients: 106 on placebo, 105 on eptastigmine 10 mg t.i.d., and 109 on eptastigmine 15 mg t.i.d. Six patients on placebo (6%), 18 patients on eptastigmine 10 mg t.i.d. (17%), and 10 patients on eptastigmine 15 mg t.i.d. (9%) discontinued study treatment. The intent-to-treat analysis on 315 patients showed a statistically significant (p=0.047) difference of 2.0 points on ADAS-Cog between the placebo and the eptastigmine 15 mg t.i.d. group at the end of treatment. Patients in the 10 mg t.i.d. group performed better than did placebo-treated patients on the Spontaneous Behavior Interview (SBI) total scores (p=0.015) and on the Activities of Daily Living (ADL, p=0.043) and Behavioral Problems (BP, p=0.028) subscales. The differences in favor of the eptastigmine groups on the CIBIC-Plus did not reach statistical significance. In a post hoc subgroup analysis by staging, the effect size of eptastigmine was found to be greater in the most severely impaired patients (Global Deterioration Scale rating of 4 and 5 at screening) reaching statistical significance in both ADAS-Cog (p=0.007) and CIBIC-Plus (p=0.038). In this patient subgroup (n=222), there was also a significant effect of eptastigmine on SBI (p=0.019). The drug was generally well tolerated, with 8% of patients withdrawing due to adverse events versus 5% on placebo. Adverse events were recorded in 35 patients (33%) on placebo compared with 41 (39%) on eptastigmine 10 mg t.i.d. and 38 (35%) on eptastigmine 15 mg t.i.d. This study shows that eptastigmine doses up to 15 mg t.i.d. for 25 weeks are well tolerated. The drug positively affects cognitive performance of Alzheimer patients. This effect appears greater in more severely impaired patients and also impacts on their behavioral performance.

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PubMed1997

Is memory loss without anatomical damage tantamount to a psychogenic deficit? The case of pure retrograde amnesia.

Following a car accident, a patient remained unconscious for approximately 20 min and confused for a few hours. When he could be questioned, he was found to have lost all past memories. The retrograde amnesia covered his whole life and concerned autobiographic events as well as famous facts and encyclopaedic knowledge. It also partially involved the verbal and visual lexicon. Reading, writing and counting were no longer possible. The profound impairment of retrograde memory contrasted with the preservation of anterograde memory, which permitted the patient to reacquire some of the notions he had lost, without, however, recovering the feeling of a personal experience of autobiographical information. Four years later, the retrograde deficit was unmodified, except for what had been relearnt. The search for data in support of an organic or psychological aetiology was negative. No signs of brain damage were apparent at the neurological examination and on CT, MRI and SPECT. On the other hand, there was no evidence of a psychiatric history, psychological stress or emotional precipitants that could substantiate the hypothesis that the patient derived a primary or secondary gain from amnesia. We propose that cases of focal retrograde amnesia, similar to the present one, deserve to be classified separately from organic and psychogenic forms under the label of 'functional' retrograde amnesia, a syndrome in which the threshold of activation of premorbid memories is abnormally raised by the trauma, leaving the encoding and retrieval of new memories unaffected.

Agraphia↗

PubMed1995

Persistent retrograde, amnesia following a minor trauma.

A 19-year-old man showed dense retrograde amnesia (RA) for autobiographical and public events covering his entire life, following a motor car accident that caused no apparent brain damage. His learning abilities remained excellent and permitted him to recover knowledge of the past, based on information gathered from other people and the media, although he never reacquired the sense of personal experience. At the onset he also showed occasional gaps in his semantic memory, e.g., he failed to recognize a few objects and was unable to provide factual information about sports he had long been playing. Eventually, his amnesia was predominantly restricted to autobiographical events or facts. After 29 months the deficit has remained unchanged. CT, MRI and PET were negative. Psychogenic amnesia was considered, but eventually ruled out for want of any evidence pointing to emotional problems, stressful situations or secondary gains. We posit that for reasons unknown a mild trauma can cause functional inhibition of the access to the engrams that are already stored, leaving intact the ability to encode and retrieve new memories.

Adult↗

PubMed1995

The 'Petites Madeleines' phenomenon in two amnesic patients. sudden recovery of forgotten memories.

We report two cases of recovery from retrograde amnesia, which occurred almost suddenly, 1 year and 1 month from onset, respectively. Amnesia followed a left thalamic infarction in one patient and a mild head trauma in the other. Full and permanent recovery occurred within a short time after the spontaneous emergence to consciousness of a single autobiographical event, triggered by the specific experience of a very similar new event. Recovery was limited to retrograde amnesia, leaving unaffected the anterograde deficit present in one of the patients. The nature (psychogenic versus organic) of our patients' memory loss is commented upon in the light of a review of previously reported cases of retrograde amnesia. The transient defect of retrograde memory is discussed in terms of a reversible distortion of the neuronal 'patterned matrices' suggested by Gloor (Brain 1990; 113: 1673-94).

Adult↗

PubMed1994

Are semantic systems separately represented in the brain? The case of living category impairment.

Following herpes encephalitis, a patient showed impaired knowledge of animals, fruits and vegetables, flowers and food (so called living things categories), whatever the modality in which stimuli were presented and responses were given. A series of experiments showed that the deficit specifically affected the ability to retrieve the perceptual features of the living stimuli defining their shape, while knowledge of their functional-encyclopedic properties was preserved. The patient had no problems with man-made objects, except when the recall of their colour, or the identification of their sound was requested. It is argued that the retrieval of the perceptual features was potentially disrupted for every type of category, but that the block was compensated for man-made objects, because the close correspondence between shape and function that characterises them provided an alternative route to access their structured form representations. On this account, the selective deficit for living categories seems contingent on the interaction between an overall cognitive impairment--the deficit in retrieving perceptual features--and some intrinsic properties of the stimulus--the factors that have modelled its form--and cannot be taken as evidence that semantic systems are allotted to separate cerebral areas.

Anomia↗

PubMed1994

Primary amnesia of insidious onset with subsequent stabilisation.

A patient had a slowly developing amnesic syndrome that remained substantially unchanged during the two and a half years of observation. Intellectual skills were excellent and there was no language, perception, praxis, or calculation deficit. The memory impairment involved verbal and visual learning, sparing spatial learning and, to a large extent, retrograde memory. Magnetic resonance imaging was normal, but PET showed a hypometabolism of the left temporal mesial region and thalamus. This case extends the spectrum of monosymptomatic cognitive disorders, previously reported in the area of language, praxis, and visual recognition, to amnesia.

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PubMed1993

The fuzzy boundaries of apperceptive agnosia.

Following a trauma that mainly involved the right hemisphere, a 21-year-old girl showed a profound impairment in visual object recognition, without language and intellectual deficit. Her elementary sensory functions were preserved and she performed in the normal range on visual matching tasks, on taks requiring to detect small differences between similar complex shapes and in copying drawings, without any evidence of a line by line approach. Her deficit emerged with tests that, though not implying identification of meaning, demanded to disentangle a form from a confused background and to achieve a highly structured description of the stimulus. In addition to this high-level perceptual processing disorder, there was a deficit in recovering from the visual store the shape of an object, also when the performance did not involve perceptual discrimination, e.g., in drawing from memory or telling the physical difference between two named stimuli. Knowledge of the semantic and contextual attributes of objects was intact. The case is taken as evidence that the borders of apperceptive agnosia may be ampler than usually thought and its distinction from associative agnosia less rigid, with some patients laying in-between the two syndromes.

Adult↗

PubMed1993

Dense retrograde amnesia, intact learning capability and abnormal forgetting rate: a consolidation deficit?

Following a thoracic trauma, which caused brain hypoxia, a 24-year-old man presented with a dense retrograde amnesia for events, persons and environments that spanned his whole life before injury. Knowledge acquired at school or through the media were equally lost, with the exception of arithmetical skills and some geographical knowledge. No deficit was apparent in language, object recognition, motor skills and intellectual tests. Anterograde memory was marked by very efficient learning capacity, an almost perfect retention of information at delay interval of 4 hours and pathologically rapid forgetting at longer delays. Informal observations agreed with test performance in showing that he could relearn facts of the past and easily acquire new information, but tended to lose these memories if the information was not frequently rehearsed. PET showed a hypometabolism of the posterior temporal lobes. Though some points remain obscure, we propose that a consolidation deficit hypothesis provides the most sensible interpretation of this peculiar pattern of memory deficit.

Adult↗

PubMed1993

Primary dyscalculia after a medial frontal lesion of the left hemisphere.

A patient had an infarct in the territory of the left anterior cerebral artery, which destroyed the medial cortex of the frontal lobe, and presented with a picture of primary dyscalculia. Lexical and syntactic processing of verbal and arabic numbers and comprehension of operation symbols were intact, but retrieval of basic, over-learned facts was mildly impaired and execution of calculation procedures was more severely impaired. As the same type of procedure could be passed or sometimes failed it suggests a deficit of activation of the appropriate procedures. The location of the lesion was unusual and suggested participation of medial frontal areas in calculation processes.

Adult↗

PubMed1992

Proper name anomia.

Following a left thalamic infarct, a patient showed a marked impairment in retrieving person proper names in response to faces and to verbal description, despite being able to provide precise information about the persons he could not name and to point to their photograph when the name was provided by the examiner. The patient was also impaired in generating proper names, but could easily retrieve common names as well as geographical names and names of monuments. It is hypothesized that the arbitrary nature of the link between proper names and their referents makes access of phonological forms from the semantic store particularly labile. In agreement with this interpretation is the patient's inability to recall telephone numbers and to learn semantically arbitrary paired associates.

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PubMed1990

Developmental dysmnesia in a poor reader.

A 22-yr-old subject with moderate developmental dyslexia experienced poor memory from an early age. In spite of normal intelligence he had great difficulty in learning historical and geographical names, mathematical formulae, poems and songs, and verbal series such as the letters of the alphabet and the months of the year. His recognition of familiar faces was also faulty at times. A battery of memory tests confirmed a moderate deficit of verbal as well as visual memory, whereas spatial memory was preserved. Other cognitive functions were intact, except for a mild reading disability. No evidence of brain pathology was provided by his history, neurological examination and CT scanning.

Adult↗

PubMed1988

Ideational apraxia.

Ideational apraxia was investigated in 20 left brain-damaged patients with tests requiring the demonstration of how objects are used. On a multiple object use test the most frequent errors were those of omission, misuse and mislocation, while sequence errors were rare. Patients also failed on a single object use test, which showed a correlation of 0.85 with the multiple object use test. Neither of these tests was significantly correlated with an ideomotor apraxia test (imitation of movements). Ideational apraxia was frequently, but not exclusively, associated with damage to the left posterior temporoparietal junction. These findings support the view that ideational apraxia is an autonomous syndrome, linked to left hemisphere damage and pertaining to the area of semantic memory disorders rather than to that of defective motor control.

Apraxias↗

PubMed1988

Perceptual attention in aging and dementia measured by Gottschaldt's Hidden Figure Test.

Gottschaldt's Hidden Figure Test (GHFT) calls for figure-ground discrimination abilities. The aim of this study was to provide a perceptual attention test for the cognitive assessment of demented patients. In Experiment 1, GHFT normal baselines on 190 healthy controls are achieved, and age-education score correction as well as transformation of the original scores into "Equivalent Scores" is established. On the inferential percentile allocation of 45 mildly-moderately deteriorated DAT patients, 65% of them performed in the critically low range of the score distribution. In Experiment 2, the discriminant power of GHFT between DAT patients and healthy controls matched by age and Experiment 2, the discriminant power of GHFT between DAT patients and healthy controls matched by age and education is assessed. Overall correct classification reached 90%. This experiment shows that GHFT in demented patients works chiefly as an attentional task. The discussion is based largely on methodological and statistical issues.

Adult↗

PubMed1987

The neurologic examination in patients with probable Alzheimer's disease.

Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.

Aged↗

PubMed1987

Ideomotor apraxia in patients with dementia of Alzheimer type.

Ideomotor apraxia was checked in a carefully selected group of patients with Alzheimer's dementia, all in the mild stage of the disease. It was shown that ideomotor apraxia is not an early neuropsychological feature. When compared with other cognitive measures, the speed of deterioration of ideomotor apraxia appears to be particularly slow.

Aged↗

PubMedDate not supplied

A 6-month, double-blind, placebo-controlled trial of eptastigmine in Alzheimer's disease.

OBJECTIVES: To evaluate the efficacy and safety of eptastigmine as a treatment for patients with mild-to-moderate Alzheimer's disease (AD). PATIENTS AND METHODS: The study was designed as a randomized, double-blind, placebo-controlled, parallel-group study. It was performed in 26 Italian and American geriatric and neurological centers. The study group comprised 349 outpatients with a diagnosis of probable AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the AD and Related Disorders Association. Patients were assigned to one of the three study groups: placebo (n = 119), eptastigmine 10 mg t.i.d. (n = 115) or eptastigmine 12 mg t.i.d. (n = 115) for 25 weeks. The AD Assessment Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB) were the primary outcome measures for efficacy. RESULTS: The two doses of eptastigmine produced similar results and are presented together. Percentages of patients completing double-blind treatment were 82 and 87% in the placebo and eptastigmine groups, respectively. At the end of treatment, the intent to-treat analysis on 342 patients showed a statistically significant effect of eptastigmine compared to placebo on both ADAS-Cog (p = 0.047) and CDR-SB (p = 0.010). Patients on eptastigmine performed significantly better than placebo-treated patients also on the Mini-Mental State Examination (p < 0.001). The drug was well tolerated with 5% of patients withdrawing due to adverse events versus 3% on placebo. Adverse events were recorded in 46% of the patients on placebo compared to 52% of the patients taking eptastigmine. Cholinergic side effects (nausea, vomiting, diarrhea and abdominal pain) were reported with similar frequency in the eptastigmine and placebo-treated patients. CONCLUSION: Eptastigmine doses up to 12 mg t.i.d. for 25 weeks are well tolerated. The drug positively affects cognitive performance and global function of patients with mild-to-moderate AD.

Aged↗