RESUMEN
The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.
Asunto(s)
Enfermedad de Alzheimer/genética , Cromosomas Humanos Par 10/genética , Predisposición Genética a la Enfermedad , Edad de Inicio , Anciano , Alelos , Apolipoproteína E4 , Apolipoproteínas E/genética , Ligamiento Genético , Marcadores Genéticos , Genotipo , Humanos , Escala de Lod , Núcleo Familiar , Oportunidad RelativaRESUMEN
Recent reports have suggested that variability in the alpha2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.
Asunto(s)
Enfermedad de Alzheimer/genética , Ligamiento Genético , Polimorfismo Genético/genética , alfa-Macroglobulinas/genética , Edad de Inicio , Alelos , Enfermedad de Alzheimer/epidemiología , Apolipoproteínas E/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Humanos , Escala de Lod , Persona de Mediana Edad , Núcleo Familiar , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
OBJECTIVE: Behavioural genetic studies of later life are strictly limited. We carried out a community-based pilot study of sibling resemblance with the primary aims of establishing the feasibility of such work in this population and estimating genetic influence on depression and its risk factors. METHODOLOGY: Data were collected on surviving siblings of individuals interviewed in previous phases of an epidemiological study of the elderly (the Gospel Oak survey); scales relevant to the investigation of late life depression and its risk factors were utilized. Since families tend to be geographically scattered, the interview was conducted by telephone. Comparisons were made between data relating to the siblings and those obtained on the probands. Variability in phenotypic traits and environmental measures was partitioned into between- and within-family variation, in order to distinguish familial and non-familial sources of variation. Intraclass correlations were used to estimate the strength of genetic influences on continuous measures, while pairwise concordances were calculated for dichotomous traits. RESULTS: Thirty-two siblings from 20 families were ultimately identified and interviewed. Intraclass correlations for the Depression and Dementia Diagnostic Scales and the Handicap Scale were 0, 0.27 and 0.22, respectively. Those for number of life events, number of friends in contact and number of neighbours in contact were 0.08, 0.03 and 0, respectively. Concordance for both depression caseness and dementia caseness was 0. DISCUSSION: There were difficulties carrying out this study, which are discussed. The study is the first of its kind to examine familial resemblance for the common disorders of old age. Establishing ways of engaging elderly families with research will be a challenge that future research will need to meet.
Asunto(s)
Trastorno Depresivo/genética , Predisposición Genética a la Enfermedad/genética , Núcleo Familiar , Fenotipo , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Femenino , Evaluación Geriátrica , Humanos , Londres , Masculino , Determinación de la Personalidad , Factores de Riesgo , Medio Social , Población UrbanaRESUMEN
OBJECTIVE: The aim of the study was to establish the concurrent validity of a telephone-administered version of the survey measures utilized in the Gospel Oak studies, the core of which was the SHORT-CARE. DESIGN: Comparisons were made between data obtained by administering the interview in its conventional, face-to-face form with those generated by conducting it by telephone. SETTING: A UK teaching hospital. PATIENTS: Elderly subjects of both sexes, recruited from geriatric and psychogeriatric day hospitals. MEASURES: The Depression Diagnostic Scale, Dementia Diagnostic Scale and Organic Brain Syndrome scale (all taken from the SHORT-CARE) and the London Handicap Scale. RESULTS: For depressive symptomatology, cognitive impairment, subjective memory impairment and handicap, intraclass correlations were 0.86, 0.89, 0.83 and 0.70, respectively. The kappa coefficient for agreement on case-level diagnosis of pervasive depression was 0.79. CONCLUSIONS: These results indicate that the instrument is broadly reliable when administered by telephone.
Asunto(s)
Demencia/epidemiología , Inventario de Personalidad/estadística & datos numéricos , Teléfono , Anciano , Anciano de 80 o más Años , Estudios Transversales , Demencia/diagnóstico , Demencia/psicología , Inglaterra/epidemiología , Hogares para Ancianos , Humanos , Incidencia , Casas de Salud , Psicometría , Valores de Referencia , Reproducibilidad de los Resultados , MuestreoRESUMEN
Pica is the persistent, culturally and developmentally inappropriate ingestion of non-nutritive substances (DSM-IV). AB is a 75-year-old lady with a 40-year history of schizophrenia and a 20-year history of pica who, at emergency laparotomy, had 175.32 Pounds of loose change in her stomach. Although pica has been reported to coexist with schizophrenia, she had had no positive symptoms of schizophrenia for at least 20 years. She has CT evidence of fronto-tempotal atrophy most marked on the left in the temporal lobe and on the right in the frontal lobe. Pica has been found to be related to cognitive deficits and hyperoral behaviour to temporal lesions. Neuropsychological testing reveals deficits closely related to these changes.
Asunto(s)
Pica/psicología , Anciano , Femenino , Humanos , Pruebas Neuropsicológicas , Pica/terapia , Esquizofrenia/complicacionesRESUMEN
BACKGROUND: Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown. AIMS: To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease. METHOD: Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis. RESULTS: Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset. CONCLUSIONS: Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders.