Publications

Dementia of the Alzheimer type (DAT) has proven to be difficult to diagnose using computerized X-ray tomography (CT). To improve the identification of DAT with CT, several different quantitative approaches have been tried. Brain parenchymal density measurements and a variety of linear indices of ventricular size have failed to reliably separate DAT patients from age matched controls. Measures of ventricular volume improve discrimination, but overlap with controls persists. The inadequacy of a single CT study to diagnose DAT is clearly related to the overlap of brain atrophy in DAT and healthy aging, a finding which has also been noted in post-mortem studies. Estimating the rate of ventricular enlargement from quantitative measurements of ventricular size on successive CT scans may allow the physician to take advantage of the progressive nature of DAT, improving separation of DAT patients from healthy controls.

Many techniques of rehabilitation require that the patient have intact cognition. This study determined the frequency of impaired cognition among the predominantly elderly patients on a community teaching hospital acute rehabilitation ward. The Cognitive Capacity Screening Examination (CCSE) was administered to 81 patients (ages 44 to 99, means 77, male:female 29:52). That 52 patients (64%) scored below 20 on the CCSE suggests significant cognitive impairment. The cognitively impaired patients were older than those with normal CCSE scores (p less than 0.05) and 19 patients had a prior history of chronic dementia. The physicians of 12 of the cognitively impaired patients (15% of all patients screened) were unaware of the impairment prior to their CCSE. Cognitively impaired patients scored similarly irrespective of a prior history of similar impairment (CCSE scores 10.2 +/- 1 for those without a prior history of dementia, 7.3 +/- 1.4 for those with prior dementia, p greater than 0.05). Physicians were more likely to be aware of a patient's current cognitive problems if the patient had a prior history of dementia (19/19 vs 21/33, p less than 0.01). The utility of employing a routinely administered CCSE to all patients accepted by a rehabilitation ward is emphasized. The time, cost, and effort of routinely performing such tests are negligible, and the potential benefits are considerable.

Cerebrospinal fluid (CSF) and serum concentrations of albumin and immunoglobulin G (IgG) were measured in 31 patients with presumptive Alzheimer's disease (AD) and in 14 healthy control subjects. The albumin and IgG quotients, and IgG index were calculated to evaluate the permeability of the blood-brain barrier and the intrathecal production of immunoglobulins. X-ray computerized tomography (CT) of the head was performed to investigate the relation between cerebral atrophy and CSF protein concentrations. The albumin and IgG quotients, and the IgG index did not differ significantly between the AD and control groups. Cerebral atrophy, as measured by CSF volume, was not related to CSF protein concentrations in either group. The results do not support the hypothesized roles of blood-brain barrier disruption or of immunologically-mediated injury of the central nervous system in the pathogenesis of AD.

One pair of monozygotic twins discordant for dementia of the Alzheimer type (DAT) was studied using neuropsychological testing, quantitative x-ray computed tomography (QCT) and magnetic resonance imaging (MRI) of the brain. Cerebral glucose metabolism was measured using positron emission tomography (PET) and 2-[18-F]fluoro-2-deoxy-D-glucose (FDG). The affected twin had a seven year history of progressive cognitive impairment and was severely demented. Neuropsychological testing of the affected twin demonstrated marked deficits in all areas of cognitive function. The asymptomatic twin showed some impairment on tests of perceptual organisation and delayed recall. The affected twin had loss of gray matter and ventricular enlargement on QCT and MRI compared with healthy controls (p less than 0.05). He also had frontal and parietal lobe hypometabolism and increased asymmetry of metabolism on PET compared to both his twin and healthy age-matched controls (p less than 0.05). PET, QCT, and MRI distinguished changes in the twin with DAT compared with his brother and healthy controls. Although the subtle neuropsychological abnormalities of the asymptomatic twin may be signs of early DAT, they were not accompanied by any changes in regional cerebral metabolism or brain structure.

We studied twelve men and six women with dementia of the Alzheimer type (DAT) and twelve healthy men at intervals of 6 months to 5 years. In the male DAT patients, mean CT rates of enlargement of third ventricle and of total lateral ventricular volumes differed significantly from zero and exceeded respective control values (p less than 0.05). The rate of neuropsychological decline correlated with rates of enlargement of the third ventricle or right lateral ventricle. Women with DAT also had significant rates of enlargement of the third and total lateral ventricles. The rate of lateral ventricular dilatation discriminated DAT patients from controls.

We measured monoamine metabolites and biopterin in the CSF of 37 patients with dementia of the Alzheimer type (DAT), with or without extrapyramidal signs, and in 14 age-matched healthy controls. Compared with concentrations in DAT and controls, the concentrations of homovanillic acid (HVA) and biopterin were significantly decreased in DAT with extrapyramidal signs (EDAT). CSF 3-methoxy-4-hydroxy-phenethyleneglycol and 5-hydroxyindoleacetic acid did not differ significantly among these groups. Age at onset of dementia was positively correlated with CSF HVA (r = 0.49, p less than 0.05). The two dementia groups did not differ significantly in the extent of ventricular dilation as measured by quantitative CT, but EDAT patients had lower Mini-Mental State Examination scores than did DAT patients. When patients were matched for age and dementia severity, CSF HVA and biopterin concentrations remained significantly lower in EDAT than in DAT patients. These results indicate that EDAT patients form a distinct subgroup of DAT with evidence of central monoamine dysfunction.

Digital and palmar dermatoglyphics were examined in 29 men and 27 women with dementia of the Alzheimer type (DAT) and 112 age-, sex-, and racial group-matched controls. Female patients had significantly (p less than 0.05) more accessory triradii and complete Sydney creases than controls; no dermatoglyphic differences were detected in the males. Separating the patients by age of onset prior to or after age 65 years did not help differentiate patients from controls by dermatoglyphic profile. This study failed to confirm either the previously reported dermatoglyphic differences between DAT patients and controls or the reported similarity of the dermatoglyphic pattern of DAT to that of Down syndrome patients.

The clinical and biological features of Alzheimer disease are not uniform in their expression; heterogeneity is evident in the disease's clinical, anatomic, and physiologic characteristics. The presence of considerable intersubject and intrasubject heterogeneity suggests that subtypes of the disease exist. We define subtypes of Alzheimer disease in regard to the behavioral features (for example, predominant right or left hemisphere, or symmetrical impairment), inheritance (familial or sporadic), dosage of chromosome 21 (presence of the Down syndrome), time course of progression, age of onset (presenile or senile), and presence or absence of motor deficit (myoclonus or signs of an extrapyramidal syndrome). Studies of regional cerebral glucose metabolism with positron emission tomography and [18-fluorine] fluorodeoxyglucose show focal alterations in glucose use, with cerebral metabolic asymmetries in patients with Alzheimer disease that are related to the nature of the cognitive deficit. Serial roentgenographic computed tomographic studies show heterogeneous rates of lateral ventricle enlargement in the disease that are related to rates of cognitive decline. Similar anatomic and physiologic abnormalities are also found in persons 45 years of age or older who have the Down syndrome. Furthermore, patients with Alzheimer disease who have extrapyramidal dysfunction or myoclonus are a distinct subgroup, with specific abnormalities of central monoamine markers of dopamine metabolism, serotonin metabolism, and the hydroxylation cofactor, biopterin. The concept of subtypes in Alzheimer disease serves as a model with which the interactions of genetic influences with environmental factors can be examined.

New brain imaging techniques may provide evidence for a biological basis for severe psychiatric disorders. The authors used quantitative X-ray computed tomography (CT) to analyze the brain volume of 10 male patients with severe primary obsessive-compulsive disorder and 10 healthy male control subjects. Caudate nucleus volume in the patients with obsessive-compulsive disorder was significantly less than that of control subjects, but lenticular nuclei, third ventricle, and lateral ventricle volumes did not differ between these two groups, and no abnormal asymmetry of bilateral structures was detected. These findings support other evidence of involvement of the caudate nucleus in obsessive-compulsive disorder.