Dementia Of The Alzheimer Type Patients Research Articles

Utility of a modified version of the wisconsin card sorting test in the detection of dementia of the alzheimer type.

Nelson's (1976) modified version of the Wisconsin Card Sorting Test (mWCST) was administered to 23 patients with mild dementia of the Alzheimer type (DAT), 33 moderate DAT patients, 31 severe DAT patients, and 75 demographically matched normal control (NC) subjects. DAT patients attained fewer categories and committed significantly more perseverative errors than NC subjects. None of the DAT patient subgroups differed in the number of perseverative errors committed, but the severe DAT patients attained significantly fewer categories than either the mild or moderate DAT patients. Receiver operating characteristic [ROC] curves were plotted to determine which among several of the measures provided the best sensitivity (i.e., correctly identified patients) and specificity (i.e., correctly identified normal controls). The number of categories attained was found to be the best discriminative measure for the entire sample of DAT patients, whereas the number of perseverative errors provided the best discriminability in mild DAT patients. Findings suggest that Nelson's original modification of the WCST is sensitive in the early detection of DAT.

Is ammonia a pathogenetic factor in Alzheimer's disease?

An attempt was made to review experimental evidence in favor of the idea that ammonia plays a role in dementia of the Alzheimer type (DAT). Hyperammonemia causes biochemical and cellular dysfunctions in the brain, which can be found in brains of DAT patients. The most conspicuous among these findings are astrocytosis, impairment of glucose utilization, and a decreased rate of energy metabolism, and the impairment of neurotransmission, with a net increase in excitability and glutamate release. The derangement of lysosomal processing of proteins is another potential site of ammonia action. This aspect is especially important in view of the growing evidence for the role of the endosomal-lysosomal system in the formation of amyloidogenic fragments from beta-amyloid precursor protein. Ammonia is not considered a primary factor of the disease. However, since hyperammonemia and release of ammonia from the brains of DAT patients is well supported by published observations, ammonia should be taken into account as a factor that contributes to manifestations and the progression of DAT. If elevated ammonia concentrations turn out to be indeed as important in DAT, as is suggested in this review, rational therapeutic avenues can be envisaged that lead to the amelioration of symptoms and progression of the disease.

Amino acid concentrations in cerebrospinal fluid and serum in Alzheimer's disease and vascular dementia.

Cerebrospinal fluid (CSF) and serum levels of 22 amino acids were studied in 13 patients with dementia of the Alzheimer type (DAT), 13 patients with vascular dementia (VD) and 15 age-matched controls. We found significantly reduced levels of glutamate in CSF samples from DAT patients compared to VD and control subjects, but CSF levels of aspartate were found to be significantly elevated in the two groups of dementia studied. Moreover, CSF concentrations of tyrosine, leucine and phenylalanine were significantly increased in VD patients in comparison with those in DAT patients and control subjects. Our results showed a wide increase in CSF/serum amino acid ratios in DAT and VD groups compared to controls. However, no differences were found in CSF/serum ratios between dementia groups. These changes show evidence for a possible disorder of amino acid metabolism with different patterns in these two dementia types.

Abnormality of bone mineral metabolism in elderly female patients with dementia

In order to clarify the relationship between dementia and osteoporosis, bone mineral metabolism was studied in elderly female patients with dementia. We measured bone mineral densities of the vertebral body and the femoral neck using DEXA, and evaluated Ca-related factors in 22 patients with dementia of the Alzheimer type (DAT), 23 patients with vascular dementia (VD), and 22 age-matched controls (C). Activity of daily living was significantly poorer in VD patients than controls, but no difference was shown between DAT and C groups. Bone mineral density values of the vertebral body and the femoral neck were significantly decreased in both DAT and VD groups when compared to C group. DAT patients showed significant decreases in serum Ca and Ca2+ ion, increase in serum parathyroid hormone, and decrease in serum 1,25-dihydroxyvitamin D, a tendency towards decrease in serum calcitonin, and a tendency towards increase in urinary Ca. However, VD patients showed only significant increase in urinary Ca and a tendency towards decrease in serum 1,2-dihydroxyvitamin D, without showing other changes of Ca-regulating hormones. These results suggest that patients with dementia are more often associated with osteoporosis, and that in DAT several abnormalities of Ca-regulating factors play an important role in the development of osteoporosis, while in VD limited physical activities contribute to bone mineral loss.

Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: a longitudinal study.

The effect of hyperglycemia on hormone levels, metabolite levels, and memory performance was examined in 22 subjects with very mild and mild probable dementia of the Alzheimer type (DAT) and in 12 normal elderly adults. Subjects were tested in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at initial and 18-month follow-up sessions. Initially, adults with very mild DAT showed memory facilitation and elevations in plasma insulin in the 225-mg/dl glucose condition relative to baseline. At follow-up, very mild DAT patients whose dementia had progressed showed significant decreases in insulin and hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels over time were correlated with memory changes for DAT subjects. These results suggest that glucoregulatory abnormalities may contribute to the pathophysiology of DAT.

Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type.

We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone responses to cholinergically active drugs in patients with dementia of the Alzheimer type.

Patients with dementia of the Alzheimer type (DAT) reportedly have reduced concentrations and function of some brain messengers, particularly acetylcholine and somatostatin, not only in the cerebral cortex, but also in subcortical structures, e.g., the hippocampus and the hypothalamus. We wished to determine the responsive pattern of DAT patients to neurohormonal and pharmacologic probes affecting growth hormone (GH) release through an interaction with hypothalamic cholinergic and somatostatinergic (SS) neurons. In 10 DAT patients, pyridostigmine (120 mg orally, p.o.), an inhibitor of acetylcholinesterase, induced an increase in GH levels similar to that elicited by the drug in age-matched controls. In 9 DAT patients, administration of GH-releasing hormone (GHRH, 1 microgram/kg body weight, intravenously, i.v.) induced an increase in plasma GH not different from that evidenced in control subjects. In DAT patients the GHRH-induced GH increase was completely inhibited by pretreatment with atropine (1 mg intramuscularly, i.m., 15 min before administration of GHRH). These findings are considered to indicate that in DAT patients, hypothalamic cholinergic and somatostatinergic neurons involved in control of somatotropic function are preserved.

Semantic memory impairment in Alzheimer's disease: Failure of access or degraded knowledge?

A battery of neuropsychological tests designed to assess semantic knowledge about the same items both within and across different modalities was administered to a group of 22 patients with dementia of the Alzheimer type (DAT) and 26 matched controls. The DAT patients were impaired on tests of category fluency, picture naming, spoken word-picture matching, picture sorting and generation of verbal definitions. A relative preservation of superordinate knowledge on the sorting and definition tests, as well as a disproportionate reduction in the generation of examplars from lower order categories was noted. Analysis of the errors made by each patient across the different tests, revealed a significant correspondence between the individual items. These findings offer compelling evidence that the semantic breakdown in DAT is caused by storage degradation.

MR‐based hippocampal volumetry in the diagnosis of Alzheimer's disease

We evaluated a new magnetic resonance (MR)-based technique for performing volumetric measurements of temporal lobe structures. The technique was designed to assist in making the clinical diagnosis of dementia of the Alzheimer type (DAT). We chose specific anatomic regions of interest because of their known involvement in memory function and in the neuropathology of DAT and used a regression model to assess the effects of age on the volumes of the anterior temporal lobe (ATL) and the hippocampal formation (HF). These measurements were normalized by total intracranial volume (TIV). The volumetric measurements of both the normalized ATL and HF were significantly smaller (p less than 0.001) in DAT patients (N = 20) than in controls (N = 22), but the HF volumes provided much better separation between the two groups. Eighty-five percent of the DAT patients fell below the range of the HF/TIV measurement for the control subjects. This separation held up over the entire age range studied. Normalized volumes of both the HF and ATL decreased with age significantly for both the DAT patients and the controls. These results support the contention that MR-based HF volumetric measurements are accurate in differentiating DAT patients from cognitively normal elderly individuals. This technique may be a useful adjunct in making the clinical diagnosis of DAT.

Visuospatial attention in dementia of the Alzheimer type.

Cue-directed shifts of spatial attention were examined for a letter-discrimination task in 15 patients with mild to moderate dementia of the Alzheimer type (DAT) and 15 healthy, age-matched controls. Spatial cues were valid, invalid or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200 ms and 2000 ms. Reaction time (RT) benefits conferred by valid cues did not differ between the DAT group and the controls. However, RT costs incurred by invalid cues were significantly greater in the DAT group than in the control group. Group differences in RT costs plus benefits occurred at short SOAs (less than 500 ms) for peripheral cues and at long SOAs (greater than 500 ms) for central cues. Reaction time costs plus benefits were correlated with right-left asymmetry in resting levels of cerebral glucose metabolism in the superior parietal lobe for DAT patients but not for controls. The results indicate that focusing of attention to spatial location is intact in early DAT, whereas the disengagement of visuospatial attention is impaired. Automatic attention shifts elicited by peripheral cues reveal abnormalities earlier than attention shifts initiated 'effortfully' by central cues. Intact focusing and impaired disengagement of visuospatial attention may be linked to dysfunction in early DAT of cortico-cortical networks linking the posterior parietal and frontal lobes.

L-Deprenyl Therapy Improves Verbal Memory in Amnesic Alzheimer Patients

Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.

Titles That May Interest You

and one chapter to each of the other species. Each chapter has a lengthy list of appropriate and current references. Clear diagrams and photographs illustrate the straightforward text. The authors seem to be aware that the volume will be read by advanced undergraduate and graduate students to keep abreast of the latest advances in a "hot" field of biology. Note the interesting error (typo?) on page 166. I will recommend Genes and Embryos as collateral reading for my own classes in genetics and to colleagues not likely to become professional developmental biologists. E. D. Garber Department of Ecology and Evolution University of Chicago Chicago, Illinois 60637 TITLES THAT MAY INTEREST YOU As a service to our readers whose specific interests span the full spectrum of the fields of biology and medicine, we are providing the titles of and relevant information about some of the books sent to us by the publishers that will not receive full review treatment. Whenever possible we will add a short description of each book. AIDS and the Health Care System. Edited by Lawrence O. Gostin. New Haven, Conn.: Yale University Press, 1990. Pp. 299. $35.00; (paper) $12.95. This comprehensive and timely review of the healdi care aspects of the AIDS epidemic comprises 19 papers grouped into eight parts, namely, policies and priorities planning for the 1990s; prevention, treatment, care, and dignity; patients ' rights and public health: confidentiality, duty to warn, and discrimination; die threat to health care workers: assessment and response; professional responsibility ; balancing hope and risk: regulation of biomedical research; the price: financing, reimbursement systems, and the financial effect on providers; and the international perspective. Alzheimer's Disease: Treatment and Long-Term Management. Edited by Jeffrey L. Cummings and Bruce L. Miller. New York: Marcel Dekker, 1990. Pp. 390. $125.00 (U.S. and Canada); $150.00 (all other countries). "Designed as a practical handbook of therapy, it is intended for family physicians , geriatricians, internists, neurologists, nurses, psychologists, social workers, and family members engaged in the care of DAT (Dementia of the Alzheimer Type) patients or their families." It purports to include all the new treatment and management approaches in a single volume. The 25 papers are grouped into four major areas of treatment interest, namely, disease-specific therapies (five papers), treatment of behavioral symptoms (four), long-term care (eight), 306 Book Reviews and future treatment directions (seven). In addition, the introductory chapter deals with the clinical diagnosis of Alzheimer's disease. TL· Animal Estate. The English and Other Creatures in the Victorian Age. By Harriet Ritvo. Cambridge and London: Harvard University Press, 1987. Pp. 347. $25.00. The author presents "a vivid picture of how animals figured in English thinking during the nineteenth century and, by extension, how they served as metaphors for human psychological needs and sociopolitical aspirations." The book combines rhetorical analysis with historical research to produce an unusual perspective on Victorian culture. Information about "people and organizations concerned with agricultural breeding, veterinary medicine, the world of pets, vivisection and other human causes, zoos, hunting at home and abroad, all revealing underlying assumptions and deeply held convictions—for example, about Britain 's imperial enterprise, social discipline, and the hierarchy of orders, in nature and human society." The Black Skimmer: Social Dynamics of a Colonial Specks. By Joanna Burger and Michael Gochfeld. New York: Columbia University Press, 1990. Pp. 355. $45.00. There has been increasing curiosity why animals form groups, and investigations have been intensifying to determine "the benefits and costs of colonial breeding in many different animals." Individual benefits include decreased time for predator detection and increasing opportunities for mate selection and predator defense. However, colonies "increase the potential for competition for mates, nest sites, and food and enhance the spread of disease and the likelihood of detection by predators." The authors have spent 15 years studying "the colonial dynamics, social behavior , and reproductive success of more than 30 black skimmer colonies." Black skimmers usually nest in mixed-species colonies with various species of terns on sandy beaches, salt marshes, and other habitats. These data should prove valuable in ensuring conservation of their habitats and their protection. TL· Dread Disease: Cancer and Modern American Culture. By James T...

Topography of the quantitative electroencephalogram in dementia of the Alzheimer type: Relation to severity of dementia

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.

Topography of the quantitative electroencephalogram in dementia of the alzheimer type: Relation to severity of dementia

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.

The contribution of list length to the absence of the primacy effect in word recall in dementia of the Alzheimer type

It has repeatedly been demonstrated that patients with dementia of the Alzheimer type (DAT) show an absence of the primacy effect when asked to recall a list of items. The results of the present study show that the absence of the primacy effect in DAT patients is related to list length but probably in a way that is qualitatively not specific since it follows the same pattern as in normal ageing. It is also demonstrated that DAT patients differ in learning style. It is suggested that this indicates a reduced capacity to maintain controlled processing.

Sleep‐wake cycles in multi‐infarct dementia and dementia of the Alzheimer type

We monitored by actigraphs minute-by-minute activity of 10 patients with multi-infarct dementia (MID), 15 patients with dementia of the Alzheimer type (DAT), and 11 control volunteers for eight consecutive 24-hour periods to assess sleep-wake cycles and sleep quality. MID patients had disrupted sleep-wake cycles associated with decreased sleep quality. In contrast, ambulatory DAT patients maintained a relatively normal sleep-wake cycle that did not differ significantly from controls. There was no correlation between the severity of intellectual deterioration and the degree of sleep-wake cycle disintegration in either group of dementia patients.

Lack of seasonal variation in the births of patients with dementia of the Alzheimer type

Seasonal variation in the birth rates of patients suffering from dementia of the Alzheimer type (DAT) was investigated in 150 patients, aged 42–88 years, and in 132 normal control subjects of comparable age and gender. No seasonal variation or cyclic trend could be demonstrated in the DAT patients compared with control subjects. The exclusion from the analysis of the patients with a positive family history did not change the results of the study, which further suggests that a seasonality in DAT birth rates is unlikely.

Quantitative CT scan analysis in senile dementia of the Alzheimer type: I. Computerized planimetry of cerebrospinal fluid areas

AbstractSixty patients with senile dementia of the Alzheimer type (DAT) and 30 age and sex‐matched healthy controls were examined by cranial computed tomography (CT). We undertook this study to evaluate a simple and unbiased quantitative method for the estimation of ventricular and subarachnoid spaces by measuring areas of defined Hounsfield units (HUs) in four symmetric quadrants: left and right anterior, left and right posterior. The DAT patients showed a significant enlargement of all ventricles and all measured subarachnoid spaces (p< 0.001). These effects were not related to the age but to the diagnosis. They correlated with the duration of disease and partly with the degree of global cognitive impairment. Seventy‐eight per cent of the patients and controls could be classified correctly by means of the planimetric measurements.

Dissociation between knowledge of living and nonliving things in dementia of the Alzheimer type

Patients who survive herpes simplex encephalitis (HSE) sometimes present a category-specific disorder for living things. Since HSE specifically involves the temporolimbic structures of both hemispheres, these structures could play a critical role in processing and storing information about living things. If this were the case, a category-specific disorder for the same items should also be observed in the early stages of dementia of the Alzheimer type (DAT) as the temporolimbic structures are often severely affected in this condition. To test this hypothesis, we administered to 15 DAT patients and to 10 normal controls a confrontation-naming task and a verbal associates recognition task, with both living and nonliving items as stimuli. The hypothesis was confirmed, since DAT patients performed worse with living than with nonliving items, and scored worse than normal controls on the living but not the nonliving items.

The biasing of weight judgments in Alzheimer's and Huntington's disease: A priming or programming phenomenon?

The performances of Huntington's disease (HD) patients and patients with dementia of the Alzheimer type (DAT) were compared on an adaptation-level task involving the judgment of weights. In this task, subjects were first exposed to either a relatively heavy (heavy bias) or a relatively light (light bias) set of weights, and were later asked to rate the heaviness of a standard set of 10 weights using a 9-point scale. Patients with DAT and intact control subjects both perceived the standard set of weights as heavier following the light bias trials and lighter following the heavy bias trials, despite the DAT patients' poor explicit memory for the initial biasing session. In contrast, the weight judgments of the HD group as a whole was not significantly influenced by prior exposure to relatively heavy or light weights, and the size of the bias effect for this group was significantly correlated with the severity of their dementia. It is suggested that the impaired biasing performance of the HD patients, like their previously demonstrated impairment in motor skill learning, is due to a motor programming deficit resulting from neostriatal dysfunction.