RESUMO
OBJECTIVES: We set to investigate the possible role of genes and environment in developing Alzheimer's disease (AD) in monozygotic twin pairs discordant for AD. METHODS: Three pairs of twins discordant for AD, who were enrolled in the Finnish Twin Cohort, were used in the study and compared with 13 controls. Gray matter changes were assessed with magnetic resonance images using voxel-based morphometry with statistical parametric mapping. RESULTS: In the affected twins, the peaks of volume loss were located bilaterally in the temporal (including the hippocampus), the frontal, and the parietal lobes, while in the unaffected siblings, the peaks were located in the frontal gyri and in the parietal lobule. Thus, in the unaffected twins, the pattern of volume loss overlaps with the neocortical but not with the medial temporal areas. DISCUSSION: These findings suggest that genetic factors more largely control neocortical regions, whereas environmental factors more strongly affect medial temporal regions.
Assuntos
Doença de Alzheimer/genética , Doenças em Gêmeos/genética , Gêmeos Monozigóticos/genética , Idoso , Doença de Alzheimer/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Doenças em Gêmeos/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Sporadic Alzheimer disease (AD) is a multifactorial disease to which both genetic and environmental factors contribute. Therefore, twin pairs are useful in studying its pathogenesis and aetiology. Cerebral glucose metabolism has been found to be reduced in AD patients. METHODS: Cerebral glucose metabolism was studied in seven monozygotic (MZ) and nine same-sexed dizygotic (DZ) twin pairs discordant for AD using positron emission tomography. To obtain objective and explorative results concerning differences in glucose metabolism, the analysis was performed utilising modern voxel-based analysis methodology statistical parametric mapping and automated region-of-interest analysis. RESULTS: In the demented MZ and DZ co-twins, cerebral glucose metabolism was extensively reduced compared with controls. The non-demented MZ co-twins showed reduced metabolism in inferior frontal, lateral temporal, parietal and medial temporal cortices as well as in the thalamus, putamen and right amygdala. In contrast, no reductions were found in the non-demented DZ co-twins. The reduction found in the non-demented MZ co-twins may be an indicator of genetic susceptibility to AD.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Glicemia/metabolismo , Encéfalo/diagnóstico por imagem , Doenças em Gêmeos/diagnóstico por imagem , Doenças em Gêmeos/genética , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Tomografia por Emissão de Pósitrons , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Radiografia , Valores de Referência , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genéticaRESUMO
OBJECTIVE: To investigate whether hippocampal atrophy, a proxy for incipient Alzheimer's disease, can be detected in non-demented monozygotic co-twins of demented twins by using volumetric magnetic resonance imaging (MRI). METHODS: Seven pairs of monozygotic female twins discordant for cognitive function (mean (SD) age 75 (4) years), and 10 age and education matched healthy controls (seven women, three men; mean age 73 (3) years) were studied with volumetric MRI. RESULTS: The mean normalised right hippocampal volume was 31% lower (p = 0.002) in the demented twins, and 6% lower (p = 0.45) in the non-demented twins than in the controls. In the left hippocampus, the mean normalised volume was 36% lower (p<0.001) in the demented twins, and 9% lower (p = 0.13) in the non-demented twins than in the controls. CONCLUSIONS: Significant hippocampal atrophy was detected in the demented twins compared with the controls. This is in line with previous imaging and pathological studies, with hippocampus showing the early changes in Alzheimer's disease. In the non-demented twins, only a minor, non-significant reduction was observed in the hippocampal volumes compared with the controls. This could reflect gene-environment interactions that have protected the non-demented twins longer than their demented co-twins and contributed to the relative preservation of their hippocampal volumes, or it could be a sign of preclinical Alzheimer's disease in the non-demented twins.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Demência/genética , Demência/fisiopatologia , Hipocampo/patologia , Idoso , Atrofia , Feminino , Humanos , Masculino , Gêmeos MonozigóticosRESUMO
OBJECTIVE: Brain acetylcholinesterase activity was determined in healthy controls and in patients with mild cognitive impairment and early Alzheimer's disease. METHODS: A specific acetylcholinesterase tracer, [methyl-(11)C]N-methyl-piperidyl-4-acetate ([(11)C]MP4A), and a three dimensional PET system with magnetic resonance coregistration were used for imaging. RESULTS: There was a significant difference in the acetylcholinesterase activity in the hippocampus between the groups (p = 0.03), the mean (SD) acetylcholinesterase activity (k(3) values, min(-1)) being 0.114 (0.036) in controls, 0.098 (0.023) in mild cognitive impairment, and 0.085 (0.022) in Alzheimer's disease. The mini-mental state examination score showed no significant relation with acetylcholinesterase activity in any brain area in the combined mild cognitive impairment/Alzheimer group. CONCLUSIONS: Hippocampal acetylcholinesterase activity is only slightly reduced in mild cognitive impairment and early Alzheimer's disease and so the value of in vivo acetylcholinesterase measurements in detecting the early Alzheimer process is limited.
