The angiotensin I converting enzyme gene as a susceptibility factor for dementia.

The frequency of a genetic susceptibility vascular factor, the deletion (D) allele of the angiotensin I converting enzyme gene (ACE), coding for a key enzyme of the renin angiotensin system, was characterized in two independent case--control studies. The results of the current study suggest that bearing at least one ACE D allele is a risk factor to develop dementia for subjects older than 74 years. This observation reinforces the hypothesis of a major implication of vascular risk factors in the occurrence of all types of dementia.

VLDL receptor polymorphism, cognitive impairment, and dementia.

OBJECTIVE: Clinical, epidemiologic, and pathologic observations suggest that vascular risk factors are associated with impaired cognition. Previous studies supported an association between cognitive decline and APOE. Although the underlying mechanism is not clear, it might involve apoE receptors, such as the very low density lipoprotein receptor. METHODS: The impact of a polymorphic triplet repeat in the very low density lipoprotein receptor gene (VLDLR) on cognitive function was examined in two independent studies: a population study involving 221 demented subjects compared with 249 control subjects and a clinical study involving 124 demented subjects compared with 179 control subjects. RESULTS: In the population study, the presence of the VLDLR-5-repeat allele was associated with a relative risk of dementia (OR, 1.9; 95% CI, 1.2 to 3.0). This result was confirmed in the clinical study (OR, 8.1; 95% CI, 4.4 to 15.1) and was more pronounced in subjects with mixed or vascular dementia than in patients with AD. CONCLUSION: The VLDLR-5-repeat allele may constitute a genetic susceptibility factor for dementia, particularly in the presence of vascular risk factors. This observation suggests the influence of vascular risk factors in the occurrence of dementia.

The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.

OBJECTIVE: To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD. BACKGROUND: The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment. METHODS: The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite AD. Paired helical filaments (PHF)-tau and Abeta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively. RESULTS: NFD with PHF-tau was systematically present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (S1), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior, temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6, the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired. CONCLUSIONS: The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.

Quantitation of Alzheimer's amyloid peptide and identification of related amyloid proteins by dot-blot immunoassay.

In Alzheimer's disease, the main component of amyloid deposits is a 39-43 amino acid peptide referred to as amyloid peptide or A beta. A crucial issue in the study of this disorder is to define the sequence of events that lead to amyloid deposition. In the present study, a new approach was developed that allows to specifically solubilize A beta peptide trapped within amyloid deposits and to quantify its amount by dot-blot immunoassay. The present method also permits to isolate components tightly bound to A beta and that are likely to catalyze its aggregation. Biochemical A beta quantitation was performed in 4 Brodmann areas from 17 elderly individuals exhibiting different degrees of amyloidosis. In parallel, classical neuropathology was done by histochemical and immunohistochemical methods. A beta amounts (pmol) were correlated to the number of amyloid deposits determined by neuropathology showing high statistical significance. Moreover, amyloid-binding proteins including apolipoprotein E and heparan sulfate proteoglycans were also found associated to A beta in the amyloid preparation. The present biochemical procedure is a new and reliable method to quantify amyloid deposition in brain. Furthermore, it allows to detect amyloid-associated components such as apolipoprotein E, that may be involved in the pathological process of amyloidogenesis.

Glial reaction in the hippocampal formation is highly correlated with aging in human brain.

Glial fibrillary acidic protein (GFAP), a biochemical marker of astrocytes and glial reaction, was quantified by immunoblotting in different brain areas from 33 non-demented patients with a Mini Mental State Examination score above 26 and aged from 12 to 98 years. An increase of GFAP with age was first found in the hippocampus and then in the entorhinal cortex. In both regions, GFAP amounts were correlated with age (r = 0.768). In the isocortex, the increase of GFAP as a function of age was also significant (r = 0.672), but less than for the hippocampal region. GFAP levels increased dramatically after the age of 65 years, and more especially in the hippocampal formation. This glial reaction was observed in aged controls that do not show cognitive impairment and the neuropathological hallmarks of Alzheimer's disease.

[Geriatrics and rehabiliation: role of the hospital in healthcare networks?]. / Gériatrie et soins de suite: place de l'hôpital au sein des réseaux de soins?

OBJECTIVE: There is no accepted definition of geriatric post-acute or rehabilitation care. The exact role within the healthcare network and the function of units providing such care remain to be clarified. We describe the activity of geriatric post-acute or rehabilitation care units in four French hospitals to identify common features and provide elements of practical interest concerning their role in the healthcare network. METHODS: Data from 4 healthcare institutions in France recorded in the 1999 Medical Information System were analyzed. RESULTS: Geriatric post-acute or rehabilitation units generally provided care for patients over 80 years of age in short-stay wards. These patients were dependent and recovering from an acute illness. In addition to rehabilitation and medical care, given according to the patients' needs, the units also provided social counseling and acute care as in other short-stay wards. A wide variety of pathological conditions was observed. At discharge most patients returned to their home or were transferred to a nursing home. CONCLUSION: Geriatric post-acute or rehabilitation units meet the requirements proposed in French legislation and in addition provide social counseling and acute care services, which is evidence of the deficiencies in the healthcare network in the field of elderly patient care.

[A new case of sarcomatous degeneration of the spine in Paget's disease of bone]. / Nouvelle observation de dégénérescence sarcomateuse du rachis Pagétique

In referring to a personal observation the authors recall the rarity of malignant degeneration of lesions of the spine caused by Paget's disease. In the majority of cases these consist of multiple centred osteo-sarcomatosis. The lumbar spine is the most often affected. The clinical picture is essentially a syndrome of radiculomedullary compression. Rapid aggravation of the condition usually leads to a neurosurgical operation, which will confirm the existence of the osteo-sarcomatous process. The evolution is always fatal.

[Normal cerebral aging: study of glial reaction]. / Vieillissement cérébral normal: étude de la réaction gliale.

Glial fibrillary acidic protein (GFAP), a biochemical marker of astrocytes and glial reaction, was quantified in different brain areas from 16 non-demented patients with a mini mental state score > 25/30 and aged from 21 to 95 years. For each brain, we analyzed the hippocampus (H), the parahippocampus gyrus (GPH) and the neocortical Brodmann areas 9, 22, 39, 44. The quantification of GFAP was performed on the different brain homogenates treated with SDS, using a Western blot method and an immunodetection with a monoclonal antibody against human GFAP. The quantity of GFAP found in the hippocampus and the parahippocampal region were significantly increased as a function of age (p < 0.001). This was not observed for neocortical areas. It has been shown that hippocampal and parahippocampal regions are specifically affected by the Alzheimer-type degenerating process during aging. Glial reaction, as visualized by immunoblotting, could be directly linked to this phenomenon.