Erich Mohr

Differential memory and executive functions in demented patients with Parkinson's and Alzheimer's disease.

Selected aspects of verbal memory and executive function were compared in 11 demented Parkinsons disease (PD) patients and 11 Alzheimers disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute.

Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles.

In an attempt to define possible subgroups of Alzheimers disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimers disease.

The functional neuroanatomy of tourette's syndrome: An FDG-PET study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourettes syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioral features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

No response to high‐dose muscarinic agonist therapy in Alzheimer's disease

Cholinergic deficiency is the most consistent transmitter system abnormality in Alzheimers disease. To test the acute therapeutic efficacy of cholinergic replacement, seven patients with presenile onset of Alzheimers type dementia received maximum tolerated doses (10 mg/d) of the selective muscarinic agonist, RS-86, in combination with a peripherally active anticholinergic glycopyrrolate (6 mg/d), in a double-blind placebo-controlled design. No consistent, clinically significant cognitive improvement could be discerned in these mild to moderately demented patients, despite attainment of central RS-86 levels approximating those that affect behavior in the experimental animal. Muscarinic agonist monotherapy may thus be inadequate to benefit Alzheimers type dementia.

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinsons disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinsons disease.

Risperidone in the treatment of dopamine-induced psychosis in Parkinson's disease: an open pilot trial.

To evaluate the safety and efficacy of risperidone in patients with Parkinsons disease (PD) who are experiencing significant dopamine‐induced psychosis.

Canadian guidelines for the development of antidementia therapies: a conceptual summary

The magnitude of the problems faced by Canadian society as a result of an aging population has been identified. Perhaps the most important concern related to this greying of Canada is the increasing incidence of dementia and Alzheimers disease. Therapeutic options for these disorders have been limited to date. Advances in biotechnology and molecular biology will offer novel approaches to treatment. These and the expansion of more traditional therapeutic avenues require guidelines with the aim of optimizing their development.

Spinal fluid CRF reduction in Alzheimer's disease

Abnormalities in several neurotransmitters, including neuropeptides, have been found in postmortem studies of Alzheimers disease (AD). Recently, corticotropin-releasing factor (CRF) was found to be diminished in cerebral cortex. In this study spinal fluid CRF-immunoreactivity (CRF-I) was determined in 16 patients with mild to moderate AD and 9 age-matched controls. Mean CRF-I levels were significantly lower in Alzheimer patients compared with controls. Furthermore, a tendency for a CRF-I increment with successive spinal fluid aliquots in control subjects was absent in Alzheimer patients. CRF-I levels failed to correlate with measures of disease severity or various tests of cognitive function. These results suggest that involvement of CRF containing neurons may play a secondary rather than a primary role in the pathophysiology of AD.

192 IgG-saporin lesion of basal forebrain cholinergic neurons in neonatal rats

Seven day old rats received bilateral intraventricular injections (200 ng) of the immunotoxin 192 IgG-saporin. When assayed in adulthood, these rats showed an 84% loss of hippocampal and a 52% loss of cortical choline acetyltransferase (ChAT) activity. ChAT was unaffected in the caudate. Cholinergic neurons immunoreactive (IR) for the low affinity neurotrophin receptor (P75NTR) were severely reduced throughout the basal forebrain nuclei. Cortical and hippocampal norepinephrine were increased and these areas showed ingrowth of ectopic, P75NTR and dopamine beta-hydroxylase IR varicosities. These were probably sympathetic axons. No obvious forebrain dysmorphogenesis was observed and cortical thickness was unaffected. These rats showed no evidence of impaired spatial learning/memory as assessed by the Morris water maze and delayed spatial alternation. However, they were less active on the elevated plus apparatus and spent less time on the open arms, suggestive of increased timidity. 192 IgG-saporin appears to be a powerful tool to selectively lesion basal forebrain cholinergic neurons in the neonatal rat. Surprisingly, the neuromorphological and behavioral sequelae seem minimal. It may be necessary to achieve near-total neonatal destruction of forebrain cholinergic neurons before severe, lasting mnemonic effects are evident.

Impairment of central auditory function in Alzheimer's disease

Accuracy and laterality of ear preference on dichotic listening (DL) takes were compared in patients with Alzheimers disease (AD) and a group of normal subjects, matched for age and education, using parameters (list length, stimulus matching, and order of recall), previously shown to significantly alter DL performance in normals. Alzheimer patients tended to show qualitatively similar, but significantly worse performance compared to controls as a function of increasing dichotic list length as well as stimulus set content (semantically, v. phonemically and unmatched dichotic items). Furthermore, these patients were unable to attend selectively to either the right- or left-ear and thus could not increase right- or left-ear advantages over the free recall procedure, an order of recall task easily mastered by the normal subjects. These results suggest that Alzheimers disease is associated with a breakdown of cortical mechanisms involved in the selective allocation of attention.