Stephen L. Read

Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease.

The authors used 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile ([18F]FDDNP), a hydrophobic radiofluorinated derivative of 2-(1-[6-(dimethylamino)-2-naphthyl]ethylidene)malononitrile (DDNP), in conjunction with positron emission tomography to determine the localization and load of neurofibrillary tangles (NFTs) and beta-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. Previous work illustrated the in vitro binding characteristics of [18F]FDDNP to synthetic beta-amyloid(1-40) fibrils and to NFTs and APs in human AD brain specimens. In the present study, greater accumulation and slower clearance was observed in AP- and NFT-dense brain areas and correlated with lower memory performance scores. The relative residence time of the probe in brain regions affected by AD was significantly greater in patients with AD (n=9) than in control subjects (n=7; p=0.0007). This noninvasive technique for monitoring AP and NFT development is expected to facilitate diagnostic assessment of patients with AD and assist in response-monitoring during experimental treatments.

Aphasia in dementia of the Alzheimer type.

Speech and language assessment in 30 patients with dementia of the Alzheimer type and in 70 normal controls revealed that all Alzheimer patients were aphasic. Throughout most of the course, the language disorder resembled transcortical sensory aphasia, and increasing language impairment correlated with increasing severity of dementia. Aphasia was present regardless of age of onset or family history of dementia. Aphasia is an important diagnostic criterion of dementia of the Alzheimer type.

Amnesia with hippocampal lesions cardiopulmonary arrest

A patient developed an amnesic syndrome after cardiopulmonary arrest. Neuropathologic examination revealed pronounced anoxic injury to both hippocampi with little damage to other hemisphere structures. The clinical and pathologic findings suggest that lesions limited to the hippocampus can cause profound amnesia.

Microvasculature in Brain Biopsy Specimens from Patients with Alzheimer's Disease: An Immunohistochemical and Ultrastructural Study

Brain biopsy specimens from five patients with Alzheimers 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.

SPECT in dementia : clinical and pathological correlation

BACKGROUND: The clinical diagnosis of dementia continues to be flawed. Although the diagnosis of Alzheimers 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.

Quantitative EEG in frontotemporal dementia.

Accurate diagnosis of the major degenerative dementias continues to be problematic. Although diagnostic precision for Alzheimers 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.

Abnormal erythrocyte choline and influx in Alzheimer's disease

Choline transport and levels were studied in erythrocytes from patients with Alzheimers disease and age-matched controls using stable isotopic tracer techniques. The mean erythrocyte choline in the Alzheimer group was 50.1 nmol ml-1 compared to 15.5 nmol ml-1 in the controls. This was significant using a Students t test at a P of less than 0.0005. Influx of choline into the erythrocyte correlated inversely with erythrocyte choline with high significance. This study suggests that erythrocyte choline is elevated in a subset of patients with Alzheimers disease and that the low affinity transport system is also abnormal in these patients. This abnormality of choline transport may play a role in the pathogenesis of Alzheimers disease in some patients.

Sustained 4-year cognitive and functional response in early Alzheimer's disease with pioglitazone.

Despite recent advances in diagnosis and treatment for individuals with ET, they remain at risk of thrombotic events, particularly in the presence of comorbidities, and as such, their identification remains a clinical priority. Whether the adoption of novel anticoagulant agents in such high-risk individuals or a more-aggressive antithrombotic treatment could lead to a lower event rate is unknown. Further trials are needed to define the correct approach to risk reduction.

Factors influencing erythrocyte choline concentrations

Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids.

Naltrexone Effects in Patients With Dementia

In their recent articles published in the Journal, Blazer and Wu (1) and Mathews and Oslin (2) have drawn attention to alcohol use among the elderly. Furthermore, a recent Treatment in Psychiatry article, by Johnson (3), highlighted pharmacologic interventions for alcoholism, where naltrexone was suggested in two out of three cases, including for a 66-year-old patient. To add to the discussion of naltrex-one use in the elderly, three cases are presented suggesting potential benefits of naltrexone for the treatment of alcoholism complicating dementia.