Functional correlates of musical and visual ability in frontotemporal dementia.

BACKGROUND: The emergence of new skills in the setting of dementia suggests that loss of function in one brain area can release new functions elsewhere. AIMS: To characterise 12 patients with frontotemporal dementia (FTD) who acquired, or sustained, new musical or visual abilities despite progression of their dementia. METHOD: Twelve patients with FTD who acquired or maintained musical or artistic ability were compared with 46 patients with FTD in whom new or sustained ability was absent. RESULTS: The group with musical or visual ability performed better on visual, but worse on verbal tasks than did the other patients with FTD. Nine had asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of FTD. CONCLUSION: Loss of function in the left anterior temporal lobe may lead to facilitation of artistic or musical skills. Patients with the left-sided temporal lobe variant of FTD offer an unexpected window into the neurological mediation of visual and musical talents.

Progression of clinical deterioration and pathological changes in patients with Alzheimer disease evaluated at biopsy and autopsy.

OBJECTIVES: To quantify the progression of senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, and microglial activation in the cortex and white matter of patients with Alzheimer disease evaluated at both biopsy and subsequent autopsy and correlate these changes with the progression of neurologic impairment. SETTING: Academic referral center for patient with Alzheimer disease. PATIENTS: Four patients meeting the clinical criteria for Alzheimer disease, enrolled in a pilot study for the evaluation of response to intracerebroventricular administration of bethanechol chloride. The patients were followed up until death occurred and autopsy was performed. RESULTS: All 4 patients had progressive deterioration from the time of biopsy to autopsy (9-11 years). Pathological investigations showed a striking increase in the density of senile plaques and neurofibrillary tangles in 2 of 4 patients from biopsy to autopsy, and a significant increase in microglial activation in 1 of 4 cases. Severity of cerebral amyloid angiopathy varied significantly among patients, 1 of whom displayed striking amyloid deposition with associated subcortical white matter atrophy. CONCLUSIONS: These unique data demonstrate that the progressive neurologic impairment in Alzheimer disease is accompanied by a significant increase in senile plaque and neurofibrillary tangle counts in the frontal cortex and, possibly in some patients, by increased microglial cell activation. Cerebral amyloid angiopathy was associated with significant white matter disease.

Quantitative EEG in frontotemporal dementia.

Accurate diagnosis of the major degenerative dementias continues to be problematic. Although diagnostic precision for Alzheimer's disease (AD) approaches 90%, for Frontotemporal dementias (FTD) it has been less than 20%. Previous work has shown that AD patients have both focal and generalized slowing, while in FTD the EEG is normal. We studied 26AD,13FTD and 27 health control subjects with Quantitative Electroencephalography (QEEG). Using only five QEEG measures with stepwise discriminant function analysis, we distinguished the AD from FTD groups each with 84.6% accuracy, and controls (100%) from FTD groups (84.6%) with high accuracy. The most informative QEEG variables for distinguishing FTD and AD were relative power from the temporal region in beta-2 band, and from the parietal region in the theta and alpha and beta-2 bands. These results suggest that QEEG may be helpful in distinguishing subjects with AD from subjects with FTD.

SPECT in dementia: clinical and pathological correlation.

BACKGROUND: The clinical diagnosis of dementia continues to be flawed. Although the diagnosis of Alzheimer's disease (AD) is better than 90% at research centers in highly selected patients, the diagnosis of patients with non-AD dementias and atypical AD patients is poor. Single photon emission computed tomography (SPECT) is a functional imaging technique touted as a diagnostic technique for the degenerative disorders. However there have been few clinicopathological studies using SPECT. METHODS: Twenty-seven consecutive dementia patients were evaluated clinically at a University-based specialty dementia clinic, and a diagnosis of a specific dementia was made. SPECT imaging was used in helping to select a clinical diagnosis. The correlations between clinical, SPECT and autopsy diagnoses were analyzed. RESULTS: Single photon emission computed tomography predicted pathologic diagnosis in 25 of 27 patients with dementia (92.6%), compared with clinical diagnosis, which was confirmed in 20/27 (74.1%). Distinct patterns were associated with dementia caused by AD, Fronto-Temporal Dementia (FTD), and Jakob-Creutzfeldt Disease (JCD). Vascular insults not seen with computerized tomography (CT) or magnetic resonance imaging (MRI) were found with SPECT. Three different pathologies were found in patients with Parkinsonian-Dementias (PD): Lewy-Body Variant of AD, Diffuse Lewy-bodies without plaques, and substantia nigra neuronal loss without plaques or Lewy-bodies. All showed a temporal-parietal pattern with SPECT that was similar to AD. CONCLUSION: SPECT provides useful positive information in dementia, particularly the differentiation of AD, FTD, and JCD. However, it does not distinguish PD from AD.

Microvasculature in brain biopsy specimens from patients with Alzheimer's disease: an immunohistochemical and ultrastructural study.

Brain biopsy specimens from five patients with Alzheimer's disease obtained in the course of a trial of intracerebroventricular bethanechol were studied by immunohistochemical (antibody to A4 peptide) and ultrastructural techniques, with particular emphasis on the microvessels. In some cases, numbers of A4-immunoreactive lesions (senile plaques) correlated well with numbers of plaques demonstrable by silver stains. Prominent A4-immunoreactive amyloid angiopathy was seen in one patient. The patient with severe cerebral amyloid angiopathy (CAA) showed extensive arteriolar deposition of amyloid filaments with apparent destruction of the media but remarkably intact endothelium. A cell of origin for amyloid filaments was not apparent, although close proximity to smooth muscle cell remnants in the arteriolar media suggested this as one possible cell of origin. Frequent vessels showed medial or adventitial collagen deposition, even when the amount of amyloid was minimal or negligible. Thus relatively severe CAA can exist in the absence of overt endothelial injury, although related studies on this tissue indicate definite abnormalities of the blood-brain barrier. Conversely, destruction of smooth muscle cells and collagen deposition in vessel walls may be the cellular correlates of arteriolar weakening that can lead to CAA-related brain hemorrhage.

Red blood cells from Alzheimer patients and from normal subjects discerned by cell electrophoresis in an aqueous polymer solution.

Blood from patients diagnosed as having Alzheimer disease and from subjects without memory impairment or dementia was collected in citrate. The erythrocytes were washed and electrophoresed in phosphate-buffered saline as well as in a number of polymer solutions in phosphate-buffered saline. The electrophoretic mobilities of red cells from Alzheimer patients and from normals were indistinguishable when measured in phosphate-buffered saline. In the dextran-rich bottom phase obtained from a dextran-poly(ethylene glycol) aqueous phase system, but not in a dextran solution alone, the electrophoretic mobilities differ (P < 0.001). In a poly(ethylene glycol) solution the mobilities also differ although, on a percentage basis, less so than in the bottom phase. It would appear that a differential adsorption of appropriately selected polymer(s) on the Alzheimer and normal red blood cells renders surface differences electrophoretically detectable.

Stable bimodal response to cholinomimetic drugs in Alzheimer's disease. Brain mapping correlates.

We investigated quantitative EEG brain mapping as a physiologic marker of drug response while studying the stability of intersubject variability in patients with Alzheimer's disease (AD) who were receiving bethanechol through intracerebroventricular (ICV) shunts. Two of the patients had previously demonstrated cognitive and behavioral improvements on medication; the third had cognitive deterioration complicated by agitated depression. All three patients were reexamined in a dose-response paradigm. Serial brain mapping examinations were performed along with brief cognitive testing. All patients showed drug responses that were comparable with responses during their initial dose-response phase. There were strong linear correlations between global decreases in 2 to 6 Hz slow-wave activity and cognitive improvement. Brain mapping demonstrated that slowing decreased in magnitude and field with increasing dose until optimal dose was reached; with supra-optimal doses, the magnitude and field of the slowing increased dramatically. These results suggest that the quality of cholinomimetic drug responses are stable over time in individual patients, and that magnitude and pattern of slow-wave activity as measured by brain mapping may be useful in monitoring treatment with cholinomimetic agents.

Intracerebroventricular bethanechol for Alzheimer's disease. Variable dose-related responses.

Five male patients participated in a pilot open-label study of dose-related aspects of response to intracerebroventricular bethanechol in Alzheimer's disease. No patient had remission of symptoms, but three patients improved symptomatically and on tests of memory. Improvement was evident over a restricted range of doses for each subject, and symptoms were worse at doses below and above the optimal range. There was little overlap in the range of doses producing improvement among these three. Two patients had no consistent improvement in memory, and agitation, depression, paranoia, and seizures developed during treatment. Qualitative differences and variability in dosages producing responses complicate the identification of true drug response in the treatment of Alzheimer's disease.

Idiopathic basal ganglia calcification and organic mood disorder.

Idiopathic basal ganglia calcification is a syndrome consisting of bilateral basal ganglia calcifications, neuropsychiatric abnormalities, disturbances of movement, and normal calcium and phosphorus metabolism. The best described neuropsychiatric alterations are dementia and an organic psychosis. Organic mood disorder has been reported less often, and mania secondary to idiopathic basal ganglia calcification has not been noted previously. The authors describe five patients with idiopathic basal ganglia calcification and organic mood changes, including one patient with secondary mania. Symptoms of idiopathic basal ganglia calcification resemble those of other disorders affecting subcortical structures and support an association between mood, affect, cognition, and the extrapyramidal nuclear system. Treatment may ameliorate the mood disorder.

Update on cholinergic enhancement therapy for Alzheimer disease.

Although patients with Alzheimer disease have a well-demonstrated deficit in cortical cholinergic markers, treatments designed to enhance cholinergic activity in the central nervous system have not achieved the clinical success of dopamine replacement for Parkinson disease. A brief review of recent clinical reports and some developments in the neurosciences suggests that it may be premature, however, to abandon the search for benefit from cholinergic enhancement therapy in Alzheimer disease.

Altered mental status in the elderly.

Misdiagnosis of treatable dementia in the aged is costly to society and the family, and is unmeasurable in personal tragedy. The 4 Ds of the elderly--dementia, depression, delirium, and delusion--are discussed. Family physicians are encouraged to seek out treatable disease.

Catatonia in thrombotic thrombocytopenic purpura: case report.

A young woman with thrombotic thrombocytopenic purpura (TTP) and a history of "catatonic schizophrenia" proved to have had a prolonged previous episode of TTP with catatonic features. TTP may present with a variety of "mental" phenomena; its pathophysiology may prove to be relevant to psychiatry. As a treatable but potentially fatal disease, its recognition is important.