Structural correlates of cognitive deficits in a selected group of patients with Alzheimer's disease.

OBJECTIVE: The objective of this study was to correlate the densities of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 patients with Alzheimer's disease (AD) with comprehensive neuropsychological data obtained within 1 year of death. BACKGROUND: Clinicopathologic studies in AD have been essentially limited to correlate neuropathologic data with severity of dementia. Very few studies have addressed the correlations between distribution of lesions and specific cognitive deficits. This is partly due to the limitation imposed by the interval between the last neuropsychological evaluation and death. METHODS: Ten patients with a postmortem diagnosis of AD, with a mean age at death of 80.4+/-6.6 years and a mean duration of symptoms of 5.6+/-2.9 years, were selected for the study. All of these patients were submitted to neuropsychological testing within 1 year of death, including 17 tests assessing memory, language, visuoperceptual, visuospatial, and constructional abilities as well as limb praxis. The neuropathologic study was performed using a modified Bielschowsky technique. Mean densities of SPs and NFTs were determined in the hippocampal formation (CA1, subiculum, and parasubiculum) and in six neocortical areas (midfrontal, orbitofrontal, cingulum, fusiform gyrus, superior and inferior parietal cortices). Statistical correlations were determined between cognitive scores and SP and NFT densities. RESULTS: For NFTs, significant correlations emerged only between tangle density in CA1 and visuoperceptual scores. For SP density values, significant correlations were found between visuoperceptual tests and lesions in the subiculum and in the fusiform gyrus, significant correlations were found between language scores and SPs in the superior parietal cortex and between visuospatial deficits and lesions in the superior parietal cortex and fusiform gyrus. CONCLUSIONS: SPs in specific brain areas displayed a good correlation with the cognitive deficits detected in this selected group of AD patients. The association of fusiform gyrus and superior parietal lobule involvement with visuoperceptual and visuospatial deficits, respectively, is in agreement with current knowledge of the anatomic basis of visual processing.

Alzheimer's disease: preliminary study of spatial distribution at birth place.

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by a progressive loss of memory and the alteration of cognitive functions. At least three chromosomal segments have been associated with early-onset AD in genetic linkage studies. These results argue for a certain degree of heterogeneity in the genetic origin of some forms of AD, although environmental risk factors cannot be ruled out in late-onset AD. In this preliminary study, we analyzed the geographical distribution of the birth places of a sample of 235 AD cases born in a defined region of Quebec (Canada), between 1895 and 1935. We wished to test the hypothesis that risk factors acting at, or around birth place and time play a role in the etiology of AD. The field of study was divided into rural and urban areas. A reference population of live births was used to compute a measure of odds ratio (OR). The OR results showed a statistically significant excess of AD cases in the rural area as compared to the reference population. When stratified for sex, the OR results showed a global excess of female AD cases in both the rural and the urban areas. For men, only the urban area presented a statistically significant deficit. We also analyzed the structures of the genealogical kinships of the rural and urban sub-groups. Although AD cases from the rural sub-group were more closely related to each other than those from the urban one, removal of the kin pairs from the OR analysis seemed to have little effect on the rural/urban distribution of cases. Therefore, the OR results would not appear to be due primarily to a difference in the kinship structures of the two sub-groups. This could mean that some risk factors for AD afflict women more strongly than men, the effect being different depending on the urban or rural origin. However, potential biases such as a higher rate of report for women, differential migration between birth places or a differential mortality ratio between sexes could produce spurious results in the direction of what we have observed in this preliminary study.

Specific pathological Tau protein variants characterize Pick's disease.

Pick's disease (PiD) is characterized by a pan-laminar frontotemporal cortical atrophy, widespread degeneration of the white matter, chromatolytic neurons, and Pick bodies (PB). Microtubule-associated Tau proteins are the main cytoskeletal components modified during the neurodegenerative changes. In the present study, pathological alterations of Tau proteins were investigated in the brains of five PiD cases at both neuropathological and biochemical levels, using the monoclonal antibody AD2 which recognizes a phosphorylation-dependent Tau epitope and strongly labeled PB. A large number of cortical and subcortical regions were studied on frozen materials. Tau proteins were analyzed on mono- and two-dimensional gel electrophoreses using a quantitative western blot approach. In all specimens, a 55 and 64 kDa Tau doublet was observed in limbic, frontal, and temporal cortices as well as in striatum and substantia nigra. In contract, Alzheimer's disease (AD) brains are characterized by the presence of the 55, 64, and 69 kDa Tau triplet whereas the 64 and 69 kDa doublet is more typical of the progressive supranuclear palsy and corticobasal degeneration. Thus, the 55 and 64 kDa doublet appears to be specific to PiD, less acidic than AD Tau proteins, and well correlated with the presence of PB.

Season of birth and Alzheimer's disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project).

The birth distribution of 399 cases of Alzheimer's disease (AD) identified in the region of Saguenay-Lac-St-Jean (Québec) was compared with that of: (a) the population currently living in the area; and (b) the population born during the same period in the same area. AD cases have been recruited since 1986 by the IMAGE Project. Cases and controls were grouped according to the month of birth and according to the day of birth using density estimation. Analyses showed a significant deficit of births in the month of May. We believe these preliminary results deserve further attention and we suggest two possible explanations that could lead to a deficit of AD births at specific periods during the year.

Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases.

Cytochrome oxidase (CO) is the terminal complex of the mitochondrial respiratory chain which generates ATP by oxidative phosphorylation. We have measured CO activity in six different brain regions of patients with senile dementia of Alzheimer type (SDAT, n = 10), presenile dementia of Alzheimer type (PDAT, n = 10), Lewy body dementia with SDAT (LBD, n = 5), cerebrovascular dementia (CVD, n = 10), Parkinson dementia (PD, n = 5), and in controls (n = 8), as all confirmed by neuropathological evaluation. CO activity was lower in the frontal and parietal cortex of SDAT patients compared to controls. Patients with PDAT, LBD, CVD or PD showed no significant reduction of the enzymatic activity in the six regions studied. Our results show that reduced CO activity might play a role in the physiopathology of senile dementia of Alzheimer type.

Consanguinity and kinship in Down syndrome in Saguenay Lac-Saint-Jean (Québec).

Genealogies of 67 cases of Down syndrome (DS) cytogenetically proven as trisomy 21 born in Saguenay-Lac-Saint-Jean were reconstructed using a population register. Genealogies of three controls for each patient matched on sex, date and place of birth were also reconstructed. The mean kinship coefficient was slightly, but not significantly (p > 0.05), increased in the DS group compared to the control group (0.000222 versus 0.000165). The increase was mostly the result of two patients being related as uncle-nephew. The mean inbreeding coefficient was also higher, although not significantly (p > 0.05), in the DS group than in the control group (0.001348 versus 0.000848). Nine consanguineous marriages (13.4%) were identified in the DS group compared to 17 of 201 (8.5%) in the control group. These results may suggest, as previously reported by Roberts et al. in Shetland, that some recessive element is involved in the etiology of DS, possibly in preventing the loss of the trisomic 21 fetus.

[Preliminary results on the residence distribution at birth of patients with Alzheimer's disease in the Saguenay-Lac-Saint-Jean/Quebec (the IMAGE project)]. / Résultats préliminaires sur la répartition lors de la naissance de sujets atteints de la maladie d'Alzheimer au Saguenay-Lac-St-Jean/Québec (projet IMAGE).

The IMAGE Project is pursuing the establishment of a population-based registry of Alzheimer's disease (AD) cases in the Saguenay-Lac-Saint-Jean (SLSJ) (Quebec). The authors report on the spatial distribution at birth of 221 possible, probable and definite cases. A large network of key-informants for screening AD cases has been established over SLSJ. The spatial distribution of cases at birth and at the onset of disease has been computed by calculating the Alzheimer birth rate (ABR) on the basis of three scales: six specific geographical spheres of screening, all municipalities, and the public health departments. The statistical significance of results was determined using the theoretical Poisson and the Chi square distributions. ABR for each of the geographical spheres of screening showed no statistically significant differences considering either residence at the onset of the disease or residence at birth. Furthermore, differences were observed between rural and urban areas with an interesting trend for a higher number of cases than expected in one area of SLSJ. The spatial distribution of cases considered on the basis of residence at birth appears to show a different pattern, but no significant, from that measured on the basis of residence at the onset of disease. Screening of cases is actively being pursued all across SLSJ by the IMAGE network. There is a clear trend towards rural residence at birth of cases. It remains to see whether or not this observation is due to a geographical concentration of familial cases.

Familial factors in Alzheimer's disease (IMAGE project). A case-control study in the Saguenay-Lac-St-Jean region (Quebec, Canada).

Alzheimer's disease is now recognized as a major public health problem. Many hypotheses have tried to explain the etiology of Alzheimer's disease and, among them, genetic factors are considered one of the most plausible. A case-control study of familial factors, including sex distribution, age at onset, birth order, parental age, fertility, mortality, inbreeding and kindship, was conducted on 130 clinically diagnosed patients born in the Saguenay-Lac-St-Jean region (Quebec, Canada). The cases were screened by the IMAGE project. Our results showed that most factors studied are not associated with Alzheimer's disease. Inbreeding was found to be slightly increased in the Alzheimer group. Kindship was higher in the Alzheimer group than in the control groups, therefore confirming that familial predisposition is a very important risk factor.

[Segmental replacement of thoracic aorta with autologous pericardium during growth (author's transl)]. / Le remplacement de l'isthme aortique par autogreffe péricardique durant la croissance.

Surgical treatment of coarctation of the aorta in the newborn often recurs during childhood. As a means of avoiding this complication segmental replacement of the thoracic aorta with autologous pericardium was evaluated. The isthmic aorta of seven mongrel puppies was replaced by a tubular live pericardial autograft. Between 5 and 36 months (average 15) after surgery, the status of the graft was evaluated by hemodynamic, angiographic, macroscopical and histological studies. Growth of the graft was appreciated by comparing its diameter to that of the descending aorta DG/DA. No pressure gradient across the graft was noted. No significant structure of the graft was observed. The internal surface of the graft was smooth, and the wall, slightly thinner than that of the aorta showed no aneurysm. The diameter of the graft was increased (DG mean 37 %) proportionally to the increase of the aorta (DA mean 36 %). Histologically the graft was endothelialized, the wall was thickened and made up of concentric collagen fibers, live fibroblasts and muscular cells. These results show that during the first months of life, the isthmus of the aorta can be replaced by an autologous pericardial graft which will follow the growth of the normal aorta and adapt to its hemodynamic regimen.