RESUMO
Antibodies reacting with neuronal cytoplasmic antigens present in normal human caudate and subthalamic nuclei were detected in 37 of 80 probands afflicted with Huntington's disease (HD). IgG antibodies were detected by immunofluorescence using frozen sections of unfixed normal human and rat brain. Specificity of IgG binding was confirmed using pepsin F(ab')2 fragments of IgG isolated from positive sera. In vitro complement fixation of IgG antibody was detected in 22 of 31 sera tested. Neuronal cytoplasmic antigens reacting with positive HD sera were diminished after trypsin or RNAase treatment of tissue sections but were not removed by DNAase, neuraminidase, EDTA, or dithiothreitol treatment. Antibody staining of neurons could be removed after absorption with isolated caudate nucleus neurons or by using perchloroacetic acid extracts of caudate nucleus. Prevalence of antibody reacting with neuronal cytoplasm was 3% in 60 normal controls and 6% among a wide variety of patients with diverse neurological disorders. However, one-third of 33 patients with Parkinson's disease showed presence of antineuronal antibody. Among patients with HD, a significant association was noted between duration of clinical disease greater than 7 yr and titers of antibody of 1:2 or greater (P less than 0.001). When 115 family members of HD probands were tested, 30% of unaffected spouses showed presence of antineuronal antibody. 23.2% of first-degree relatives at risk for developing HD was also positive (P less than 0.001). 10.5% of second-degree relatives showed presence of antineuronal antibody. These data may support an environmental or infectious factor somehow involved in the ultimate expression of HD.
Assuntos
Anticorpos/análise , Núcleo Caudado/imunologia , Diencéfalo/imunologia , Doença de Huntington/imunologia , Adulto , Idoso , Testes de Fixação de Complemento , Feminino , Imunofluorescência , Humanos , Doença de Huntington/genética , Fragmentos Fab das Imunoglobulinas , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The number, size, density and pathologic alterations of myelinated fibers (MF) of ventral and dorsal roots and of peroneal and sural nerves in groups of female Fischer 344 rats at 10, 20, and 30 months of age were evaluated to characterize nerve changes with old age. Except for minimal changes in the peroneal nerve, no statistically significant alteration in number of MF/nerve or in the fascicular area was associated with aging. The unaltered number was misleading since striking changes in MF size distribution, pathologic alterations of fibers and the presence of regeneration clusters suggested age-related degenerative and regenerative events. These changes were most dramatic in the ventral root, where myelin infolding, myelin separation from axon and ballooning, macrophagia and hyperplasia of Schwann cell nuclei were pronounced. Concomitant with these alterations, axonal atrophy (a reduction in caliber of axons relative to myelin spiral length or number of myelin lamellae) was demonstrated in MF of the ventral root in old age.
Assuntos
Envelhecimento/fisiologia , Fibras Nervosas Mielinizadas/crescimento & desenvolvimento , Animais , Axônios/ultraestrutura , Feminino , Microscopia Eletrônica , Bainha de Mielina/ultraestrutura , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/ultraestrutura , Condução Nervosa , Ratos , Ratos Endogâmicos F344 , Raízes Nervosas Espinhais/crescimento & desenvolvimento , Raízes Nervosas Espinhais/patologia , Raízes Nervosas Espinhais/ultraestrutura , Fatores de TempoRESUMO
The authors conducted an extensive pharmacological analysis of a patient severely affected by tardive dyskinesia. No drug treatment gave lasting clinical improvement. Several agents recently recommended for this condition, dimethyl aminoethanol, clozapine, and thioridazine, failed to modify the dyskinesia. Reserpine caused a worsening of the symptoms. A paradoxical and unexpected improvement was observed with apomorphine injections and with low-dosage oral L-dopa. These two drugs may have acted by stimulating presynaptic inhibitory dopamine receptors.
Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Apomorfina/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Levodopa/uso terapêutico , Adulto , Amantadina/uso terapêutico , Benzotropina/uso terapêutico , Clozapina/uso terapêutico , Deanol/uso terapêutico , Dextroanfetamina/uso terapêutico , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Tolerância a Medicamentos , Feminino , Haloperidol/uso terapêutico , Humanos , Levodopa/administração & dosagem , Fisostigmina/uso terapêutico , Receptores Dopaminérgicos/efeitos dos fármacos , Reserpina/efeitos adversos , Estimulação Química , Tioridazina/uso terapêuticoRESUMO
Seven patients had superior sagittal sinus thrombosis diagnosed by cerebral arteriography. We recommend that anticoagulants not be used in the therapy of this entity, but rather that one should rely on antiedematous agents and anticonvulsants.
Assuntos
Trombose dos Seios Intracranianos/tratamento farmacológico , Adulto , Anticonvulsivantes/uso terapêutico , Anticoncepcionais Orais/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Heparina/uso terapêutico , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez , Radiografia , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/etiologiaRESUMO
A 38-year-old man developed pain and peripheral-type weakness on the right side of his face and was discovered to have decreased hearing bilaterally, as well as optic nerve swelling on the right. The pain and optic nerve swelling subsided over a period of six weeks, but hearing loss and facial weakness persisted. Thirty months later, he developed dysphagia, ataxia, dysarthria, nystagmus, and progressive spastic quadriparesis. He died approximately four years after the onset of the illness. Although no evidence of disease was found other than in the central nervous system during life, two nodules in the right lower lung were found on autopsy. The examination of these nodules, as well as the brain stem, showed an angiocentric and angionecrotic process with lymphoreticular and plasmacytoid invasion.
Assuntos
Encéfalo/patologia , Granuloma/patologia , Vasculite/patologia , Adulto , Cerebelo/patologia , Humanos , Pulmão/patologia , Masculino , Ponte/patologiaRESUMO
OBJECTIVE: To calculate average annual incidence rates for Huntington's disease (HD) from 1950 through 1989 and to estimate prevalence rates of the disease for January 1, 1960, and January 1, 1990. DESIGN: Health care records from all sources, including hospitals, outpatient clinics, and long-term care institutions, are readily available for all inhabitants of Olmsted County, Minnesota. The diagnoses entered in these records have been coded and indexed. All health care records containing a diagnosis that might suggest HD were reviewed, and those patients for whom the symptoms of HD began between January 1, 1950, and December 31, 1989, were identified. We used specific criteria for diagnosing HD. PARTICIPANTS: Health care records were reviewed; residence in Olmsted County during the year of symptom onset was required. MAIN OUTCOME MEASURES: Average annual incidence rates and prevalence rates for January 1, 1960, and January 1, 1990. RESULTS: Overall incidence rates were 0.4 (95% confidence interval [CI], 0.1 to 0.8) for women and 0.2 (95% CI, 0.04 to 0.6) for men per 100,000 person-years. Estimated prevalence rates for January 1, 1960, per 100,000 person-years were 6 (95% CI, 0.7 to 21.5) for women and 6.6 (95% CI, 0.8 to 23.8) for men. For January 1, 1990, the prevalence rates were 1.8 (95% CI, 0.04 to 10.2) for women and 2 (95% CI, 0.05 to 10.9) for men. CONCLUSIONS: Incidence and prevalence rates of HD in this community are similar to those reported in other communities. The small numbers of affected persons do not allow an estimate of variation over time.
Assuntos
Doença de Huntington/epidemiologia , Feminino , Humanos , Incidência , Masculino , Minnesota/epidemiologia , PrevalênciaRESUMO
The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided.
Assuntos
Doença de Alzheimer/psicologia , Demência/psicologia , Transtornos da Memória/psicologia , Entrevista Psiquiátrica Padronizada , Idoso , Humanos , Inteligência , Pessoa de Meia-Idade , Psicometria , Escalas de WechslerRESUMO
OBJECTIVE: To confirm the putative hypersensitivity of the pupil to a weak mydriatic in persons with Alzheimer dementia. DESIGN: Twenty patients with Alzheimer dementia and 20 control subjects were examined. Automated binocular infrared pupillography was performed in the dark after instillation of 0.01% tropicamide or placebo. Ocular penetration of eye drops was assessed simultaneously using 2% fluorescein sodium as a tracer. SETTING: Rochester, Minn. SUBJECTS: Twenty patients and 20 cognitively normal control subjects from the Alzheimer's Disease Patient Registry of the Mayo Clinic, Rochester, Minn. MAIN OUTCOME MEASURE: Percent change in the diameter of the pupil following topical ocular instillation of a diluted concentration of the mydriatic drug tropicamide and penetration of topically applied fluorescein into the aqueous humor. RESULTS: No statistically significant difference was found between patients with Alzheimer disease and control subjects in either the mydriatic response of the pupil or in the rate of penetration of topically applied fluorescein. CONCLUSION: No evidence of pupillary hypersensitivity to an anticholinergic mydriatic drug was found in patients with Alzheimer disease or any evidence that this putative hypersensitivity could be used as an early, simple diagnostic test for Alzheimer disease.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Pupila/efeitos dos fármacos , Pupila/fisiologia , Tropicamida/farmacologia , Idoso , Feminino , Humanos , Masculino , Midríase , PlacebosRESUMO
BACKGROUND: Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. OBJECTIVE: To characterize clinically subjects with MCI cross-sectionally and longitudinally. DESIGN: A prospective, longitudinal inception cohort. SETTING: General community clinic. PARTICIPANTS: A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. MAIN OUTCOME MEASURES: The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. RESULTS: The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. CONCLUSIONS: Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
Assuntos
Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Memória , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Transtornos Cognitivos/classificação , Transtornos Cognitivos/diagnóstico , Demografia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos ProspectivosRESUMO
We ascertained the incidence of dementias of all causes between 1960 and 1975 among citizens of Rochester, Minnesota. Study of all medical records yielded incidence rates for the quinquennial periods of 1960-1964, 1965-1969, and 1970-1974. In the population at risk (30 years or older), the age-adjusted rates (per 100,000 population/year) for Alzheimer's disease (clinically diagnosed or pathologically confirmed, or both) in the three periods were: 104.9, 80.8, and 96.6. The rates for dementia of all causes were: 160.6, 122.0, and 136.8. Calculation of 95% confidence intervals showed that the incidence rate for dementia or Alzheimer's disease has not changed in this 15-year period in Rochester, Minnesota. Assuming no demented patients younger than 29 years, the incidence rates in the three quinquennial periods for all dements were 79.4, 60.3, and 67.7; for Alzheimer's disease they were 51.9, 40.0, and 47.8.
Assuntos
Demência/epidemiologia , Doença de Alzheimer/epidemiologia , Feminino , Humanos , Masculino , MinnesotaRESUMO
The clinical records and autopsy protocols were studied from 350 cases in which an autopsy was done in Olmsted County, MN, in 1980 and 1981. Overall autopsy rate was 33.6%, and autopsy rate for those aged 60 years or more was 29%. Preselected criteria were used for diagnosis of dementia. Thirty-two demented and 68 nondemented patients had complete autopsies; all were more than 60 years old. Twenty-three of 32 (72%) demented patients had Alzheimer's disease. The frequency of cerebral infarcts among the nondemented patients was significantly higher than among the demented patients (p = 0.02).
Assuntos
Demência/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Autopsia , Infarto Cerebral/diagnóstico , Demência/patologia , Humanos , Pessoa de Meia-Idade , Minnesota , Estudos RetrospectivosRESUMO
Records of all patients diagnosed as having an "empty" sella turcica at the University of Michigan Medical Center after 1972 were retrospectively reviewed. Nineteen patients satisfied the two criteria, absence of prior surgical or radiotherapeutic intervention and air within the sella turcica at pneumoencephalography. Associated clinical signs and symptoms were varied and nonspecific. Two patients had relative visual field deficits without increased intracranial pressure. Three patients had papilledema and were diagnosed as having had benign increased intracranial pressure. Increased intracranial pressure was not a consistent enough finding to be considered an etiology for the empty sella syndrome.
Assuntos
Doenças da Hipófise/fisiopatologia , Sela Túrcica , Adolescente , Adulto , Idoso , Feminino , Cefaleia/etiologia , Humanos , Pressão Intracraniana , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome , Transtornos da Visão/etiologia , Campos VisuaisRESUMO
Using the centralized diagnostic data resource for the population of Rochester, Minnesota, we determined the prevalence of medically diagnosed dementia for this community. There were 289 individuals with dementia who were residing in Rochester on January 1, 1975: 208 women and 81 men. The overall age- and sex-adjusted rates per 100,000 population were 342 for all dementias and 227 for Alzheimer's disease. Prevalence rates increased with age for both sexes. Limiting the denominator to persons greater than or equal to 65 years, age-adjusted rates per 100,000 population for men and women were 3,452 and 3,466 (or about 3.5%), respectively, for dementia and 2,007 and 2,675 (2.0 and 2.7%), respectively, for Alzheimer's disease.
Assuntos
Demência/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Fatores Sexuais , Estados UnidosRESUMO
Using the resources of the Rochester Epidemiology Project, we conducted a case-control study of sociodemographic characteristics using the incidence cohort of patients with Alzheimer's disease (AD). During the conduct of ongoing studies of AD in Rochester, we identified new cases of AD as they occurred during 1975-1979 (N = 241). We selected one age- and sex-matched control from among all registrations for care in this community during the year of onset for each case. There was little difference between cases and controls for educational attainment, marital status, type of dwelling, living arrangement, or occupation. We were unable to confirm low educational level as a risk factor for AD in this population. Future attempts to identify etiologic risk factors for dementing illness should probably move toward other areas of research.
Assuntos
Doença de Alzheimer/epidemiologia , Idoso , Estudos de Casos e Controles , Escolaridade , Feminino , Habitação , Humanos , Incidência , Masculino , Estado Civil , Ocupações , Análise de Regressão , Fatores de RiscoRESUMO
We identified all incident cases of clinically diagnosed Alzheimer's disease among the population of Rochester, MN, with onset from 1965 through 1974. A control (selected from the same community) was matched to each case by age, race, sex, and length of stay in Rochester. We studied 274 case-control pairs. Using the records linkage system available for residents of this community, we abstracted information on the occurrence of head trauma with loss of consciousness (LOC) from the medical records of both cases and controls. There were 5 pairs in which the case suffered an episode of head trauma with LOC but the control did not, and 4 pairs in which the control suffered an episode of head trauma with LOC but the case did not. We failed to detect a statistically significant difference between the 2 groups. This study overcomes many problems encountered in previous case-control studies reporting this association. The sample size was large; severity of head injury was documented in high-quality medical records; data about head injury were recorded before the onset of dementia: equal quality of data were available for cases and controls; and, since the study was population-based, there was no selection bias for cases or controls.
Assuntos
Doença de Alzheimer/etiologia , Traumatismos Craniocerebrais/complicações , Inconsciência , Estudos de Casos e Controles , Traumatismos Craniocerebrais/fisiopatologia , Métodos Epidemiológicos , Humanos , Fatores de Risco , Fatores de TempoRESUMO
We compared the point prevalence rates of dementing illnesses in the population of Rochester, Minnesota, on January 1, 1980, with the previously published rates of January 1, 1975, by using extensive health care records available from all sources of care in the community, in order to identify and classify cases with standard diagnostic criteria derived from DSM-III. The overall age- and sex-adjusted prevalence rate per 100,000 population for dementia on January 1, 1980, was 402.5 compared with 388.4 on January 1, 1975; for Alzheimer's disease it was 259.8 in 1980 and 259.5 in 1975. The stability of the rates suggests no change in the incidence and mortality associated with these conditions. The prevalence rates for Rochester, Minnesota, are similar to many other rates estimated in other North American communities, but they differ from two other population-based estimates from East Boston and California. Case definitions and methods of assessment probably account for the differences in estimated prevalence.
Assuntos
Demência/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de TempoRESUMO
Few risk factors have been identified for dementing illness to date. To evaluate prior therapeutic radiation exposure as a potential risk factor for Alzheimer's disease, we carried out a retrospective case-control study using the Rochester Epidemiology Resource. Cases were all incident cases of AD from 1960 through 1974 (N = 392) identified in an ongoing study of the condition in this community. One age- and sex-matched control for each case was selected from all registrations for care during the year of onset in the case. There were 86 cases and 89 controls with prior radiation exposure, and the variable used to describe exposure was absorbed dose. Most of the exposure was small doses: 11 individuals received greater than 1,000 centigray (3 cases, 8 controls). Using the logistic regression methods of Breslow and Day, the estimated odds ratio for any prior therapeutic radiation exposure was 0.95 (95% CI, 0.66 to 1.37). When the exposure variable was limited to head exposure only, the odds ratio was 0.65 (95% CI, 0.32 to 1.31). It is unlikely that the risk associated with therapeutic radiation in the development of Alzheimer's disease is greater than 1.4.
Assuntos
Doença de Alzheimer/etiologia , Radioterapia/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de RiscoRESUMO
We report the survival experience of the incidence cohort of Alzheimer's disease (AD) patients in Rochester, Minnesota, whose onset occurred during the years 1960 to 1984. Survival was evaluated relative to year of onset, age at onset, and gender. Survival was better among women than men and improved for those with AD with more recent onset. The relative hazard decreased by a factor of 0.82 for each decade. The effect of age at onset was nonlinear, indicating that the hazard of death does not change at a constant rate with age.
Assuntos
Doença de Alzheimer/mortalidade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Minnesota/epidemiologia , Modelos de Riscos Proporcionais , Fatores Sexuais , Análise de Sobrevida , Taxa de SobrevidaRESUMO
The detection of very early Alzheimer's disease (AD) can be important for both theoretical and practical reasons. Typically, a memory impairment is the first sign of incipient disease, but the early clinical diagnosis can be challenging. We investigated several aspects of memory function in AD and normal aging to determine which indices of performance were most sensitive at detecting early impairments. We evaluated 106 pairs of patients with probable AD and matched controls from the Mayo Clinic Alzheimer's Disease Patient Registry using a logistic regression model that included measures of memory function, verbal and nonverbal intelligence, attention, and language. Results indicated that an index of learning, especially with semantic cuing, was most sensitive at separating the two groups. We then matched subsets of individuals from the larger groups of AD and control subjects on the Mini-Mental State Examination (range of scores, 24 to 26). A logistic regression analysis on these matched groups yielded the same results. A measure of learning with facilitation of performance using cues appears to be the best discriminator at detecting very mild AD. These measures can be useful in selecting patients for interventional strategies.
Assuntos
Doença de Alzheimer/diagnóstico , Transtornos da Memória/diagnóstico , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Escalas de Graduação Psiquiátrica , Estatística como AssuntoRESUMO
We evaluated memory function in a group of 161 community-dwelling, cognitively normal individuals aged 62 to 100 years recruited as part of the Mayo Clinic Alzheimer's Disease Patient Registry. We used the Free and Cued Selective Reminding Test and the Rey Auditory Verbal Learning Test to evaluate two aspects of memory function thought to be sensitive to the effects of aging: learning (acquisition) and delayed recall (forgetting). The results were quite consistent and demonstrated that learning or acquisition performance declines uniformly with increasing age but is not related to education. Delayed recall or forgetting, however, remained relatively stable across age when adjusted for the amount of material initially learned. These findings are relevant for assessing normal memory function relative to the early impairments found in dementia and form a baseline against which memory performance can be assessed by the clinician. In particular, suspicion regarding a disorder of brain function affecting memory processes should be raised if learning performance declines more rapidly than expected or if delayed recall is impaired to any significant extent.