A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. (65/3586)

Familial Danish dementia (FDD), also known as heredopathia ophthalmo-oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia. Neuropathological findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer's disease. N-terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia. Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795-796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267. The decamer duplication mutation produces a frame-shift in the BRI sequence generating a larger-than-normal precursor protein, of which the amyloid subunit (designated ADan) comprises the last 34 C-terminal amino acids. This de novo-created amyloidogenic peptide, associated with a genetic defect in the Danish kindred, stresses the importance of amyloid formation as a causative factor in neurodegeneration and dementia.  (+info)

Neuropsychological changes after surgery for anterior communicating artery aneurysm. (66/3586)

Neuropsychological disturbances following surgery for anterior communicating artery aneurysms were analyzed in 26 patients (11 males, 15 females) using the Hasegawa dementia scale-revised (HDS-R) over a 3-year period. The patients were aged from 34 to 76 years (mean 54.1 years). Lesions in the frontal lobe were evaluated using computed tomography (CT). Twenty-three patients had symptoms over the course. Four patients had basal forebrain lesion, five had ventral frontal lesion, and 12 had no lesion. Patients with basal forebrain lesion and no lesion tended to show disorientation. The mean HDS-R score was 10.2 points in the patients with ventral frontal lesion, and 13.5 points in the patients with no lesion. These scores are within the range for dementia. The mean HDS-R score in patients with basal forebrain and striate lesions was over 25 points and beyond the range for dementia. Significant differences were observed in the HDS-R score between patients with ventral frontal lesion and basal forebrain lesion, and between patients with no lesion and basal forebrain lesion (p < 0.05). Recovery from neuropsychological disturbances was poorer in patients with ventral frontal lesion and no lesion compared to those with basal forebrain and striate lesions, and their symptoms tended to persist.  (+info)

Would you like to know what is wrong with you? On telling the truth to patients with dementia. (67/3586)

OBJECTIVES: To discover what dementia sufferers feel is wrong with them; what they have been told and by whom, and what they wish to know about their illness. BACKGROUND: Ethical guidelines regarding telling truth appear to be equivocal. Declarations of cognitively intact subjects, attitudes of family members and current psychiatric practice all vary, but no previous research has been published concerning what patients with dementia would in fact like to know about their diagnosis and prognosis. DESIGN: Questionnaire study of the patients' opinions. SETTING: Old Age Psychiatry Service in Worcester. PARTICIPANTS: 30 consecutive patients with dementia. RESULTS: The quality of information received has been poor and many patients have no opportunity to discuss their illness with anybody. Despite that almost half of the participants in this study had adequate insight and a majority declared that they would like to know more about their predicament. CONCLUSIONS: Although many patients would like to know the truth, the rights of those who do not want to know should also be respected. Therefore the diagnosis of dementia should not be routinely disclosed but (just as in other disorders) health care professionals should seek to understand their patients' preferences and act appropriately according to their choice.  (+info)

Decisions to treat or not to treat pneumonia in demented psychogeriatric nursing home patients: development of a guideline. (68/3586)

Non-treatment decisions concerning demented patients are complex: in addition to issues concerning the health of patients, ethical and legal issues are involved. This paper describes a method for the development of a guideline that clarifies the steps to be taken in the decision making process whether to forgo curative treatment of pneumonia in psychogeriatric nursing home patients. The method of development consisted of seven steps. Step 1 was a literature study from which ethical, juridical and medical factors concerning the patient's health and prognosis were identified. In step 2, a questionnaire was sent to 26 nursing home physicians to determine the relative importance of these factors in clinical practice. In a meeting of nine experienced physicians (step 3), the factors identified in step 2 were confirmed by most of these professionals. To prevent the final guideline being too directive, a concept guideline that included ethical and legal aspects was designed in the form of a "checklist of considerations" (step 4). Experts in the fields of nursing home medicine, ethics and law reviewed and commented on the concept guideline (step 5). The accordingly adapted "checklist of considerations" was tested in a pilot study (step 6), after which all experts endorsed the checklist (step 7). The resulting "checklist of considerations" structures the decision making process according to three primary domains: medical aspects, patient's autonomy, and patient's best interest (see annex at end of paper).  (+info)

Ubiquitin immunochemistry as a diagnostic aid for community pathologists evaluating patients who have dementia. (69/3586)

Alzheimer's disease is the most common cause of dementia It is associated with genetic risk factors and at least three autosomal dominant mutations. Community pathologists are frequently asked by families to evaluate autopsy material for Alzheimer's disease. Neuropathologic diagnosis is based on technically difficult silver impregnation stains that may not be readily available to community-based pathologists. Because immunohistochemical techniques are more widely accessible, we evaluated the practical utility of using a single immunohistochemical stain for diagnosing Alzheimer's disease. The ubiquitin antigen was selected because of its presence in morphologically distinct deposits characteristic of several neurodegenerative diseases. Paraffin blocks were obtained from the Bryan Alzheimer's Disease Research Center Brain Bank, a repository of approximately 900 brains. Tissues from 16 individuals who exhibited the entire range of Alzheimer's-type neuropathology were selected. Ubiquitin immunostains, evaluated blindly and independently by four pathologists ranging from first-year resident trainee to experienced neuropathologist, reliably stained both neuritic plaques and neurofibrillary tangles essential for diagnosing and staging Alzheimer's disease. Nondemented controls with early Alzheimer's-type changes were easily distinguished from cases of definitive Alzheimer's disease. The stains also highlighted characteristic inclusions of Parkinson's disease or Lewy body dementia Ubiquitin immunohistochemistry is a reliable, reproducible, and readily available diagnostic aid for distinguishing Alzheimer's disease from other causes of dementia.  (+info)

Ageing and learning disability. (70/3586)

BACKGROUND: Ageing is a continuation of the developmental process and is influenced by genetic and other biological factors as well as personal and social circumstances. AIMS: To identify some key biological, psychological and social issues relevant to how ageing might particularly effect people with learning disabilities. METHOD: This selected review considers the extent to which there are similarities and differences relative to people without learning disabilities. RESULTS: There is a convergence, in later life, between people with a learning disability and those without, owing to the reduced life expectancy of people with more severe disabilities. People with Down's syndrome have particular risks of age-related problems relatively early in life. CONCLUSIONS: The improved life expectancy of people with learning disabilities is well established. There is a lack of a concerted response to ensure that the best possible health and social care is provided for people with learning disabilities in later life.  (+info)

The plasma homocysteine concentration is better than that of serum methylmalonic acid as a marker for sociopsychological performance in a psychogeriatric population. (71/3586)

BACKGROUND: Cobalamin/folate deficiency in elderly subjects may lead to psychiatric symptoms, but more often it increases the severity of various organic and nonorganic mental diseases. A major clinical problem, however, is the uncertainty and controversy concerning biochemical markers of cobalamin/folate deficiency to be used in the diagnostic evaluation of suspected cobalamin/folate deficiency. METHODS: We measured plasma homocysteine (tHcy), blood folate, serum methylmalonic acid, and serum cobalamin in 80 psychogeriatric patients (age, 77.3 +/- 8.6 years) and 50 controls (age, 76.1 +/- 8. 0 years). We assessed associations of these tests with measures of cognitive and behavior performance by use of regression analyses. RESULTS: Plasma tHcy was increased in 45% of the psychogeriatric population (mean, 20.5 +/- 9.2 micromol/L vs 15.3 +/- 4.7 micromol/L for controls; P <0.01). Plasma tHcy correlated with severity of dementia (r = 0.36; P <0.01), the Katz ADL index (r = 0.29; P <0.05), the Berger scale (r = 0.29; P <0.05), and the score of symptoms (r = 0.39; P <0.001) in the psychogeriatric population. Similarly, blood folate was significantly correlated with these measures, but the concentrations of serum cobalamin and methylmalonic acid were not. In a stepwise multiple regression analysis including the biochemical markers, tHcy was the only significant predictor of the severity of dementia (r(2) = 0.11; P <0.01) and the score of symptoms (r(2) = 0.16; P <0.001). CONCLUSION: Plasma tHcy is the best marker of those measured to investigate suspected tissue deficiency of cobalamin/folate.  (+info)

Clinical aspects of dementia in African-American, Hispanic, and white patients. (72/3586)

This article examines the relationship between ethnicity, cognitive deficits, functional impairment, and psychiatric symptoms in patients with dementia. The data are from a cross-sectional study of patients evaluated at the Northern California Alzheimer's Disease Center (ADC). Using the ADC database of patient information, the authors compared sociodemographic and clinical variables in 187 African-American patients, 69 Hispanic patients, and 1317 white patients with Alzheimer's disease (AD), ischemic vascular dementia (IVD), and mixed dementia (AD/IVD). Multivariate analysis indicated the following results: 1. African-American patients and Hispanic AD patients had lower risk of depressed mood compared to white patients; 2. African-American patients had lower risk for anxiety than whites; 3. Hispanic patients with mixed dementia had lower rates of apathy compared to whites. Future studies are needed to examine how ethnic group differences in dementia are based on the interaction of cultural differences; effects of age, education, and psychosocial variables; and biological differences in the course of dementia.  (+info)