RESUMO
Results of a standardized histochemical and immunocytochemical analysis of the brains of 14 nondemented elderly humans for whom prospective neurological and neuropsychological data had been collected for 3 to 8 years before death suggested that nondemented elderly humans fall into two pathological subgroups that are not clinically distinguishable. One was associated with moderate to marked cerebral amyloid deposition ("pathological aging"), while the other had either minimal or no amyloid deposition ("normal aging"). Neocortical and hippocampal neurofibrillary degeneration was either completely absent or of very limited degree in both subgroups. Both subgroups had ubiquitin-immunoreactive dystrophic neurites in the cerebral cortex and granular degeneration of myelin in white matter. These ubiquitin-immunoreactive structures seem to be a universal and invariant manifestation of brain aging, but the same cannot be said for amyloid deposition and neurofibrillary degeneration. Pathological aging might be preclinical Alzheimer's disease, but it currently cannot be distinguished from normal aging by even sensitive neuropsychological measures. These findings provide strong support for the hypothesis that cerebral amyloid deposition is not necessarily associated with clinically apparent cognitive dysfunction and that additional factors, such as neuronal or synaptic loss or widespread cytoskeletal aberrations, are necessary for dementia in AD.
Assuntos
Envelhecimento/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Benzotiazóis , Angiopatia Amiloide Cerebral/patologia , Córtex Cerebral/patologia , Feminino , Lobo Frontal/patologia , Hipocampo/patologia , Humanos , Imuno-Histoquímica , Masculino , Transtornos da Memória/patologia , Degeneração Neural , Emaranhados Neurofibrilares/patologia , Estudos Prospectivos , Valores de Referência , Tiazóis , Ubiquitinas/imunologia , Córtex Visual/patologia , Escalas de WechslerRESUMO
Prediction of the functional outcome for patients with stroke has depended on the severity of impairment, location of brain injury, age, and general medical condition. This study compared admission and discharge functional outcome (Functional Independence Measure, FIM) and deficit severity (Fugl-Meyer, F-M) scores in a retrospective study of patients with similar neurologic impairments: homonymous hemianopia, hemisensory loss, and hemiparesis. CT-verified stroke location was the independent variable: cortical (n = 11), basal ganglia and internal capsule (normal cortex and thalamus, n = 13), or combined (cortical, basal ganglia, and internal capsule, n = 22). By 3 months on average after stroke, all groups demonstrated significantly improved motor function as measured by F-M scores. Patients with cortical lesions had the least CT-imaged damage and the best outcome. Patients with combined lesions and more extensive brain injury had significantly higher FIM scores (P < 0.05) than patients with injury restricted to the basal ganglia/ internal capsule. Patients with basal ganglia/internal capsule injury were more likely to have hypotonia, flaccid paralysis, and persistently impaired balance and ambulation performance. While all patients had a comparable rehabilitation experience, these results suggest that patients with stroke confined to the basal ganglia and internal capsule benefited less from therapy. Isolated basal ganglia stroke may cause persistent corticothalamic-basal ganglia interactions that are dysfunctional and impede recovery.
Assuntos
Doenças dos Gânglios da Base/reabilitação , Transtornos Cerebrovasculares/reabilitação , Idoso , Doenças dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/fisiopatologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Hemianopsia/etiologia , Hemianopsia/fisiopatologia , Hemiplegia/etiologia , Hemiplegia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Estudos Retrospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
Identification of elderly individuals with low and high risk for future dementia has emerged as an important clinical and public health issue. To address this issue, we assessed neuropsychological performance in 317 initially nondemented elderly persons between 75 and 85 years of age and followed them for at least 4 years as part of the Bronx Aging Study. Four measures of cognitive function from the baseline assessment (delayed recall from the Buschke Selective Reminding Test, recall from the Fuld Object Memory Evaluation, the Digit Symbol subtest from the Wechsler Adult Intelligence Scale, and a verbal fluency score) can identify one subgroup with an 85% probability of developing dementia over 4 years and another with a 95% probability of remaining free of dementia. The model achieved an overall positive predictive value of 68%, or three times the base rate, for prediction of the development of dementia in our sample. The overall negative predictive value for prediction of absence of dementia was 88%. Baseline measures of cognitive function, often performed many years before the actual diagnosis of dementia, can provide important information about dementia risk. The group likely to develop dementia becomes a target for preventive or early therapeutic interventions, and the group unlikely to develop dementia can be reassured.
Assuntos
Idoso/psicologia , Demência/psicologia , Testes Neuropsicológicos , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Valor Preditivo dos TestesRESUMO
Sixteen patients with early Alzheimer's disease (AD) completed a 3-month outpatient double-blind parallel trial of oral physostigmine versus placebo. Ten subjects received drug; six received placebo. After a dose-titration phase, each patient was placed on his or her best dose of drug or placebo. Subjects were evaluated with both memory and nonmemory tasks. Seven of the ten drug-treated patients, but none of the six placebo-treated patients, demonstrated improvement on a selective reminding task, a test of verbal memory. Family members reported improvement in six of ten drug-treated patients and none of six placebo-treated individuals. There was a trend toward greater improvement with increasing drug dose. There was no improvement on the nonmemory tests administered. The data indicate that oral physostigmine improves memory but not other areas of cognition.
Assuntos
Doença de Alzheimer/psicologia , Memória/efeitos dos fármacos , Fisostigmina/uso terapêutico , Atividades Cotidianas , Administração Oral , Idoso , Doença de Alzheimer/tratamento farmacológico , Método Duplo-Cego , Humanos , Fisostigmina/administração & dosagem , Fisostigmina/farmacologia , Testes PsicológicosRESUMO
OBJECTIVE: To examine the relationship of the Berg Balance Scale (BBS) to outcome after acquired brain injury. METHODS: Forty consecutive patients with acquired brain injury were admitted for multidisciplinary rehabilitation. Patients were assessed with the BBS. The BBS was originally designed as a quantitative measure of balance and risk for falls in community-dwelling elderly patients. The BBS comprises 14 different tasks graded on a 56-point scale. Community-dwelling elders with a BBS score of < or = 42 have > 90% risk for falls. RESULTS: In our study, there were 27 patients with a low BBS score (< or = 42) and 13 patients with a high BBS score (> or = 43). The discharge total Functional Independence Measure (FIM) scores were lower in the low BBS patients (96.4 +/- 21.2) compared with the high BBS patients (111.5 +/- 12.5) (p < 0.007). The length of stay (LOS) was significantly longer in the low BBS patients (38.9 +/- 18.5 days) compared with the high BBS patients (14.2 +/- 6.1 days; p < 0.000). Among the three patients that experienced falls during their hospitalization, all exhibited low BBS scores. The admission BBS score strongly correlated with admission total FIM scores (r = 0.86; p < 0.000) and moderately correlated with discharge total FIM scores (r = 0.56; p < 0.000) and LOS (r = -0.55; p < 0.000). Using a multiple regression analysis, the admission FIM score was found to be the better predictor of discharge FIM scores, and time admitted after injury was the better predictor of LOS. CONCLUSIONS: Prediction of rehabilitative outcome might be enhanced by the use of the BBS scores in combination with other clinical measures on admission to inpatient acute rehabilitation.
Assuntos
Atividades Cotidianas , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/reabilitação , Acidentes por Quedas/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/epidemiologia , Técnicas de Diagnóstico Neurológico , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
In rodents, transient forebrain ischemia causes preferentially neuron death in small and medium size neurons of the striatum and hilar neurons in the hippocampus within 24 h, and CA1 hippocampal neurons within 72 h. The temporal unfolding of pathological processes after longer time intervals between reperfusion and sacrifice now includes delayed degeneration of the substantia nigra reticulata (SNr). Animals were exposed to 20 min of transient forebrain ischemia and sacrificed within 7 days, or at least 3 weeks after reperfusion. Histological examination and quantitative morphometrics revealed that the degree of volume loss and neuron loss in the SNr depended on the initial ischemic injury. Initial ischemic injury confined to the caudate nucleus produced volume loss but not neuron loss in the SNr. However, initial ischemic injury that included the caudate nucleus and the globus pallidus produced not only greater volume loss but also neuron loss in the SNr. SNr neuron loss was restricted to the medial dorsal area, occurred in animals that survived at least 3 weeks after perfusion, and did not occur in animals that survived 7 days after perfusion, and was accompanied by increased staining of antibody to glial fibrillary acidic protein. The topographic specificity and delayed time course suggest that the mechanism for SNr neuron loss depends on transneuronal events initiated by ischemia but evolving over a longer time period. In situ hybridization with a cDNA probe for glutamic acid decarboxylase (GAD) mRNA demonstrated increased GAD signal in the remaining SNr neurons of animals with CN and GP damage compared to animals with CN damage. The significant increase in GAD mRNA may indicate compensation at the level of gene expression for the loss of GABAergic neurons. This rodent model offers new in vivo opportunities to elucidate the requirements for neuronal viability, and phenotypic expression, and suggests that the current notions of windows of opportunity for therapeutic intervention may be expanded from hours to days to weeks.
Assuntos
Expressão Gênica , Glutamato Descarboxilase/biossíntese , Ataque Isquêmico Transitório/patologia , Neurônios/patologia , Prosencéfalo/patologia , Substância Negra/patologia , Ácido gama-Aminobutírico/metabolismo , Animais , Sondas de DNA , Proteína Glial Fibrilar Ácida/análise , Ataque Isquêmico Transitório/metabolismo , Neurônios/metabolismo , Prosencéfalo/metabolismo , Células Piramidais/metabolismo , Células Piramidais/patologia , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ratos , Valores de Referência , Reperfusão , Substância Negra/metabolismo , Fatores de TempoAssuntos
Agressão/fisiologia , Encéfalo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Sítios de Ligação , Cricetinae , Diencéfalo/metabolismo , Di-Hidroalprenolol/metabolismo , Feminino , Humanos , Sistema Límbico/metabolismo , Mesencéfalo/metabolismo , Mesocricetus/metabolismo , Especificidade da EspécieRESUMO
Selected drugs were tested for effectiveness in reducing dieldrin retention by rats. Female rats were fed diets treated to contain 1 ppm dieldrin. The drugs were administered as feed additives or by i.p. injections. The rats were sacrificed after 10 days of treatment and abdominal adipose tissue was analyzed for dieldrin using electron capture gas chromatography.Heptabarbital (40 and 225 mg/kg rat/day), aminopyrine (75 and 350 mg/kg rat/day), tolbutamide (60 and 290 mg/kg rat/day), and phenylbutazone (90 mg/kg rat/day) were effective as feed additives in reducing tissue dieldrin. Heptabarbital was the most effective and reduced the concentration of tissue dieldrin by 80 per cent at the higher dose level. In comparison, DDT (4 mg/kg rat/day) effected a 72 per cent reduction. A contrast with DDT was also observed in trials with i.p. administration of drugs and DDT. In those trials, the duration of the DDT action was apparently greater than that of the drugs.We suggest that suitable drugs might be used to reduce insecticide accumulation in the tissues of animals and man, and for treatment of individuals after over exposure to insecticides.
RESUMO
Transneuronal degeneration (TND) of neurons in the substantia nigra reticulata (SNR) occurs after initial ischemic or neurotoxin damage to the striatum. The mechanism is incompletely understood. In rats ibotenic acid (IBO) lesion of the caudate nucleus (CN) and the globus pallidus (GP) caused, 3 weeks later, a 47% loss of neurons (P < 0.001) in the SNR. Rats with IBO lesion confined to either the CN or the GP had SNR neuron numbers comparable to control. The volume of the SNR was decreased, as expected, in all groups with striatal lesions. To test whether the subthalamic nucleus (STN) played a role in the demise of SNR neurons, the STN was lesioned 1 week before animals were exposed to CN and GP injury. STN ablation prevented the expected SNR neuron loss. Based on the current information about basal ganglia anatomy, an imbalance between GABAergic and glutamatergic afferents may have caused TND in the SNR. These results suggest that the potential for the release of intrinsic excitotoxicity exists within certain anatomic networks.
Assuntos
Degeneração Neural , Neurônios/fisiologia , Substância Negra/patologia , Substância Negra/fisiopatologia , Núcleos Talâmicos/fisiopatologia , Animais , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/patologia , Globo Pálido/efeitos dos fármacos , Globo Pálido/patologia , Ácido Ibotênico/farmacologia , Masculino , Neurônios/patologia , Ratos , Ratos WistarRESUMO
In a prospective study of dementia in initially normal functioning elderly, a brief form of the Fuld Object-Memory Evaluation (OM) was administered to 474 cognitively normal community-residing volunteers aged 75-85 at baseline and annually thereafter. Seventy-two subjects later became demented. Memory test data from the last annual evaluation before cognitive change was noted were available for 56. Although the entire population recalled 7.28 (SD = 1.33) of the 10 objects on Trial 1 of the test at baseline, these 56 subjects recalled only 5.96 (SD = 1.85). When recall of 6 or fewer objects was used as a predictor, the OM test identified 32 of the 56 who subsequently became demented. Compared to an estimated base rate of 15% for dementia, the predictive value of a positive test (PV+) was 39%, and that of a negative test (PV-) was 89%. With a cutoff of 5 or fewer items recalled, the PV+ rose to 59% and the PV- was 94%. Although the OM test was only moderately sensitive to incipient dementia (.57), it was fairly specific (.84), and lowering the cutoff to 5 increased the specificity to .96. Memory testing would therefore seem to hold promise as a predictor of dementia in cognitively normal elderly.
Assuntos
Doença de Alzheimer/diagnóstico , Percepção de Forma , Rememoração Mental , Testes Neuropsicológicos , Retenção Psicológica , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Valores de ReferênciaRESUMO
The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia.
Assuntos
Doença de Alzheimer/diagnóstico , Rememoração Mental , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo , Estudos Prospectivos , Retenção Psicológica , Aprendizagem VerbalRESUMO
Neurones in the rat substantia nigra compacta (SNC) are initially resistant to transient forebrain ischaemia in contrast to vulnerable neurones in the striatum that die within 24 h. Animals were exposed to 20 min of four vessel occlusion and killed 1 and 3 weeks after reperfusion. All ischaemic animals had striatal neurone loss. Analysis of the number of tyrosine hydroxylase immunoreactive neurones (THir) in the SNC was comparable between controls and ischaemic animals killed 1 week after reperfusion. However, there was a significant reduction in THir neurone number (24%), SNC volume (17%), and THir dendritic arborization in the substantia nigra reticulata (SNR) that occurred 3 weeks after reperfusion, despite the persistence of THir axons in the striatum. Detailed morphological analysis of areas distant from the initial ischaemic injury suggest delayed degeneration may play an important role in the brain's response to ischaemia, and may provide insights for clinical stroke treatment and management.
Assuntos
Ataque Isquêmico Transitório/patologia , Neurônios/patologia , Prosencéfalo/irrigação sanguínea , Substância Negra/patologia , Análise de Variância , Animais , Ratos , Fatores de TempoRESUMO
The selective reminding (SR) procedure, a popular technique for the study of verbal memory, was used to investigate aspects of memory functioning in a large group of normal elderly and in a smaller group of elderly subjects with Alzheimer Type Dementia (ATD). One hundred thirty-four normal elderly (mean age = 79.53 years) subjects and 21 ATD subjects (mean age = 68.3 years) were administered four versions of the SR test as part of a longitudinal study of risk factors in the development of dementia. Normative data were obtained for multiple components of memory functioning within the elderly sample. Test-retest reliability was .84 for long-term retrieval (LTR), .89 for sum of recall, and .92 for consistent retrieval. Clinical validity studies revealed that the components of sum of recall, storage estimate, LTR, and consistent long-term storage (CLTS) were most valuable in distinguishing mild ATD from normal aging. Positive predictive values ranged from 86% for CLTS, 89% for LTR, 91% for sum of recall, and 100% for storage estimate. These findings suggest that the SR test has considerable clinical utility in differentiating normal aging from dementia, and has promise as a useful tool in the preclinical detection of ATA.