Biomedical subjects
J Victoroff
Publications and source records attributed to J Victoroff.
Increased apolipoprotein E mRNA in the hippocampus in Alzheimer disease and in rats after entorhinal cortex lesioning.
The distribution of apolipoprotein E (ApoE) mRNA was characterized in the hippocampus of humans with Alzheimer disease (AD) and in rats with experimental lesions (unilateral ablation of the entorhinal cortex) that model selected features of AD. In both AD and the lesion model, we observed a shift in the location of astrocytes containing prevalent ApoE mRNA from the neuropil to regions with densely packed neurons. The increased abundance of ApoE mRNA in astrocytes close to neuron cell bodies could be indicative of lipid uptake in regions where neurons are degenerating or where synaptic remodeling is taking place.
Caregiver and clinician assessment of behavioral disturbances: the California Dementia Behavior Questionnaire.
As part of a multicenter project to study noncognitive behavioral disturbances in dementia, the authors developed a comprehensive caregiver-rated questionnaire for these behaviors. The authors determined the reliability of caregiver ratings and compared caregiver ratings with clinician ratings using standard instruments. Caregivers showed good test/retest reliability for ratings of all types of patient behavioral disturbance. Caregiver interrater reliability was highest for depression and lowest for psychosis. The correlation between caregiver reports and professional assessments was highest for agitation, intermediate for psychosis, and lowest for depression. The match between caregiver and clinician assessments of patient behaviors appears to vary significantly by the type of behavior assessed.
Physical aggression is associated with preservation of substantia nigra pars compacta in Alzheimer disease.
OBJECTIVE: To investigate specific neuropathologic correlates of agitation and physical aggression in Alzheimer disease (AD). DESIGN: Neuronal counts in the nucleus basalis, locus ceruleus, and substantia nigra were compared in the brains of patients with pathologically definite AD with or without histories of agitation or interpersonal violence. SETTING: Alzheimer disease center of a university department of neurology. MAIN OUTCOME MEASURES: Neuron densities in the nucleus basalis and absolute neuron counts in the locus ceruleus and substantia nigra pars compacta. RESULTS: The patients with AD who had histories of unequivocal interpersonal violence had significantly greater neuron counts in the substantia nigra pars compacta than did the nonviolent patients with AD. This finding remained significant after multiple clinical and neuropathologic variables were adjusted for. Neuropathologic findings in the nucleus basalis and locus ceruleus were not different between violent and nonviolent patients. CONCLUSION: Preservation of pigmented substantia nigra neurons may be a risk factor for physical aggression in AD.
Multicenter clinicopathological correlation in dementia.
OBJECTIVE: The aim of the present study was to determine the accuracy of clinical diagnoses of dementia in a large group of patients evaluated in a multicenter, university-based, Alzheimer's disease diagnostic and treatment program. METHOD: Clinical diagnoses and neuropathological results from seven collaborating Alzheimer's disease research centers were compared for 196 cases of dementia. RESULTS: When diagnoses of probable Alzheimer's disease, possible Alzheimer's disease, and Alzheimer's disease plus another condition were combined, 163 (83%) of the patients were clinically regarded as likely to have had Alzheimer's disease. Of those patients, 134 (82%) were found to have neuropathological changes diagnostic of Alzheimer's disease or Alzheimer's disease plus another condition. A total of 116 patients were diagnosed as having probable Alzheimer's disease; 100 (86%) of those were found to have pathological diagnoses of Alzheimer's disease or Alzheimer's disease plus another condition. Cerebral infarcts were found in 17% of the patients clinically diagnosed with probable Alzheimer's disease. Lewy bodies with variable Alzheimer's disease-type pathological changes were found in 7% of the patients with clinical diagnoses of probable Alzheimer's disease. Conversely, significant Alzheimer's disease-type pathological changes were found in 55% of the patients clinically diagnosed as having vascular dementia. CONCLUSIONS: Clinicians accurately predict Alzheimer's disease-type neuropathological findings in a high proportion of cases of dementia but may not predict cerebrovascular pathology and Lewy bodies in some patients with apparent clinical Alzheimer's disease and may often fail to predict Alzheimer's disease-type pathological findings in patients with apparent vascular dementia. With the emergence of effective treatments for Alzheimer's disease, there is an increasing need to optimize methods for ante-mortem diagnosis of dementia.
Posterior cortical atrophy. Neuropathologic correlations.
OBJECTIVE: A subgroup of patients with progressive dementia has been reported with a marked predominance of symptoms attributed to the dysfunction of the posterior parieto-occipital cortex. These cases have been referred to as posterior cortical atrophy. The objective of this study was to determine whether posterior cortical atrophy is associated with distinct, uniform neuropathologic findings. DESIGN: Three individuals with progressive dementia that began with higher visual dysfunction (posterior cortical atrophy) were followed up to definitive neuropathologic diagnosis. RESULTS: Three separate neuropathologic entities were discovered: subcortical gliosis, Alzheimer's disease, and Creutzfeldt-Jakob disease. CONCLUSION: Posterior cortical atrophy is a clinically homogeneous but pathologically heterogeneous syndrome.
A method to improve interrater reliability of visual inspection of brain MRI scans in dementia.
MR scanning is used in the clinical evaluation of patients with dementia but lacks a reliable method of visual inspection. Two neurologists conducted multiple pilot trials of alternate methods for visual inspection of MRIs, including methods that produced at least 75% interrater agreement in repeat trials, and selected a final method for rating ventricular:brain ratio (VBR), cortical atrophy, and white matter changes. Two other neurologists, new to the method, tested interrater reliability for each component of the method after a brief training session. The correlation of VBR measurement was 0.884 (p = 0.0001). The weighted kappa scores were 0.68 for overall frontal lobe atrophy, 0.38 for right temporal lobe atrophy, 0.20 for left temporal lobe atrophy, and 0.54 for parietal lobe atrophy. The weighted kappa scores were 0.77 for overall periventricular white matter hyperintensities and 0.72 for centrum semiovale hyperintensities. The proposed method may provide a rapid and reliable way to assess VBR, frontal lobe atrophy, parietal lobe atrophy, and white matter changes on brain MRIs in the evaluation of dementia, but it was less reliable for the assessment of temporal lobe atrophy.
The evolution of aging-related brain change.
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Psychiatric complications of dementia: impact on caregivers.
This study was designed to determine the relationship between psychiatric features of dementia and their impact on caregivers. 35 patient-caregiver pairs were evaluated at two university-affiliated dementia clinics, using standard instruments to rate patient psychiatric features and caregiver burden and depression. There were highly significant correlations between patient agitation and both caregiver burden (r = 0.59, p = 0.0002) and depression (r = 61, p = 0.0001). These associations remained significant after adjusting for multiple demographic and dementia variables. There was no significant association between patient delusions, hallucinations, or depression and caregiver burden or depression. Agitation, particularly physical aggression, may impact caregivers even more than does the cognitive status of the demented patient.