Journal - Human genetics (GERMANY )

Abstract :

A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50 years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer's disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.

Journal - Acta neurologica Scandinavica. Supplementum (DENMARK )

Abstract :

Dementia is a descriptive term derived from the Latin root de mens, indicating an observable decline in mental abilities. It is an acquired clinical syndrome characterised by deterioration of mental functioning in its cognitive, emotional and conative aspects. The concept is comprehensive with several different clinical profiles and courses. The diagnosis of dementia implies that several mental faculties are involved and exclude isolated neuropsychiatric disturbances such as amnesia and aphasia which occur with focal brain lesions. Description and classification of dementia conditions have however to deal with the problem that the word "dementia" might have different meanings in different contexts. It might denote a clinical syndrome irrespective of etiology, but also imply that the etiology of this syndrome is brain dysfunction. Moreover, the term dementia is sometimes used in a wider sense to describe the underlying brain disease from its early subtle manifestations to advanced stages of severe deterioration. By definition this deterioration previously was progressive and irreversible with little hope for the patient. Clinical experience however has changed our views, and it is now accepted that the course of dementia can be progressive, static or remittent.

Journal - Dementia and geriatric cognitive disorders (SWITZERLAND )

Abstract :

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by progressive neuronal loss and microvacuolization, although with different distributions of cortical involvement. In contrast to AD there is no amyloid, senile plaques or tangles in FTD. The involvement of chromosome 19 in AD has been associated with apoliprotein E (ApoE) and the epsilon 4 gene frequency has been related to increased risk and early onset of AD. Our analysis of frequency of the ApoE alleles in 38 patients with AD, 21 patients with FTD and 29 normal controls indicates an association of both AD and FTD with an increased frequency of the epsilon 4 allele and in AD also with homozygosity for epsilon 4. Our results might indicate that ApoE epsilon 4 is an important aggravating and pathoplastic factor in the presence of genetic and other determinants for the development of AD or FTD. A significantly higher epsilon 2 frequency in our FTD material compared to AD and normals might also indicate a connection with the distribution of cortical degeneration.

Journal - Acta neurologica Scandinavica. Supplementum (DENMARK )

Abstract :

The cholinergic hypothesis of Alzheimer's disease (AD) was tested in two doubleblind crossover studies. Physostigmine given intravenously to 10 AD patients for two hours caused improvement of reaction time and EEG and increased regional cerebral blood flow (rCBF) in the temporoparietal cortex. 17 AD patients (mean age 62.6 +/- 6.8 years) obtained three types of treatment: tetrahydroaminoacridine (THA), THA + lecithin and placebo in randomized order. Each treatment period was 6 weeks. The mean THA dose was 104 +/- 20 mg/day. There were differences in outcome between groups of patients over the total 26 weeks treatment period. The subclassification in responders, unchanged and deteriorated was supported by rCBF, EEG and psychometric testing.

Journal - Acta neurologica Scandinavica. Supplementum (DENMARK )

Journal - Clinical autonomic research : official journal of the Clinical Autonomic Research Society (ENGLAND )

Journal - Advances in neurology (UNITED STATES )

Journal - Archives of gerontology and geriatrics (NETHERLANDS )

Abstract :

In a longitudinal prospective study of dementia, 158 patients were investigated post mortem. Sixteen patients were classified as frontal lobe dementia (FLD) of non-Alzheimer type and four cases as Pick's disease. Positive heredity for dementia was reported in 50% of these cases compared to 30% in a reference group of patients with Alzheimer's disease (AD). The typical clinical picture in FLD and Pick's disease was that of a slowly progressive dementia, at an early stage dominated by personality change, lack of insight, disinhibition, and later on stereotypy and increased apathy. There was also a progressive dynamic aphasia ending in mutism and amimia. Memory and spatial functions were comparatively spared. Disinhibition, oral/dietary hyperactivity, and echolalia were more consistently found in Pick's disease compared to FLD. The differential diagnosis against AD, cerebrovascular dementia, and other degenerative dementias and against affective disorders and psychotic reactions are discussed.