Comparison of neurologic changes in 'successfully aging' persons vs the total aging population.

OBJECTIVE: To determine age-related changes in neurologic function in the general population. DESIGN: To administer a neurologic examination to participants in such a way that it is possible to calculate the proportion of elderly persons in the population with each abnormal finding and the proportion of persons with each finding but without evidence of the medical and neurologic diseases likely to produce neurologic abnormalities (eg, stroke and diabetes). SETTING: Individuals were selected from a community-dwelling population. PARTICIPANTS: A stratified random sample of 467 persons aged 65 years and older were evaluated. RESULTS: Many neurologic abnormalities are increasingly common with advancing age and are present in a substantial portion of the elderly population. The prevalence of abnormal neurologic findings not attributable to disease, however, is substantially lower, typically one half to one third the total prevalence. Moreover, the increase with age in the prevalence of abnormal neurologic findings not attributable to major disease varies substantially among the different measures. CONCLUSIONS: Primitive reflexes and measures of gait show statistically significant increases with age in multiple measurement domains, suggesting a selective age-related vulnerability.

Correlates of headache in a population-based cohort of elderly.

Data from a community-based study of 3811 persons aged 65 years and older were used to describe the characteristics of headache in the elderly. Subjects were asked whether they experienced headache in the past year, the frequency and severity of their headaches, and whether they experienced three symptoms of migraine: unilaterality, nausea or vomiting, an aura preceding the headache. Prevalence of headache in those aged more than 65 years declined with age in both men and women; women had a higher prevalence in each age group. The same was true for frequent, severe, and migrainous headache. We examined age- and sex-adjusted correlations of headache with several medical and social factors. Prevalence of any headache was strongly associated with joint pain, depression, bereavement, waking during the night, use of eyeglasses, symptoms of temporomandibular joint dysfunction, and self-assessment of health. Similar variables were associated with frequency, severity, and migrainous symptoms, and thus could not be distinguished among these various types.

Extrapyramidal signs and other neurologic findings in clinically diagnosed Alzheimer's disease. A community-based study.

The association between findings on the neurologic examination and the clinical diagnosis of Alzheimer's disease was investigated among 467 individuals from a geographically defined community population. Participants were selected by stratified random sampling based on their memory performance in a population survey of community residents 65 years of age and older. Each participant underwent a structured medical, psychiatric, neurologic, and neuropsychologic examination. Of the 467 persons examined there were 134 cases of probable Alzheimer's disease and 167 control subjects. Multiple logistic regression analysis was used to estimate the degree to which the presence of each of several neurologic examination findings affected the age- and sex-adjusted relative odds of having clinically diagnosed Alzheimer's disease. The most striking associations with the diagnosis of Alzheimer's disease were seen with various measures of extrapyramidal dysfunction. These increased relative odds were not markedly affected by excluding from the analysis cases with severe cognitive impairment. The results suggest that involvement of the extrapyramidal system is a common finding in Alzheimer's disease.

Adaptation to lateral displacement of vision in patients with lesions of the central nervous system.

The visual-motor adaptation to lateral displacement of vision by prism glasses was studied in normal individuals and patients with cerebellar dysfunction, Parkinson's disease, right or left cerebral hemisphere lesions, Alzheimer's disease, or Korsakoff's syndrome. Adaptation was analyzed in two phases, the return to normal pointing with prism glasses in place (the "error reduction portion") and the mispointing in the opposite direction after the glasses were removed (the "negative aftereffect portion"). Negative aftereffect, which seems to be the best measure of true adaptation, was significantly reduced only for the cerebellar patients. This poor performance supports the involvement of the cerebellum in motor learning.

Broca aphasia: pathologic and clinical.

The speech disturbance resulting from infarction limited to the Broca area has been delineated; it differs from the speech disorder called Broca aphasia, which results from damage extending far outside the Broca area. Nor does Broca area infarction cause Broca aphasia. The lesions in 20 cases observed since 1972 were documented by autopsy, computerized tomography, or arteriogram; the autopsy records from the Massachusetts General hospital for the past 20 years and the published cases since 1820 were also reviewed. The findings suggest that infarction affecting the Broca area and its immediate environs, even deep into the brain, causes a mutism that is replaced by rapidly improving dyspraxic and effortful articulation, but that no significant distrubance in language function persists. The more complex syndrome traditionally referred to as Broca aphasia, including Broca's original case, is characterized by protracted mutism, verbal stereotypes, and agrammatism. It is associated with a considerably larger infarct which encompasses the operculum, including the Broca area, insula, and adjacent cerebrum, in the territory supplied by the upper division of the left middle cerebral artery.

Abnormal cisternogram associated with Diamox therapy.

A cisternogram characteristic of normal-pressure hydrocephalus was obtained from a patient on Diamox who was being evaluated for rapid mental deterioration. A repeat cisternogram after Diamox was discontinued was nearly normal. We hypothesize that the initial abnormality resulted from reduced cerebrospinal fluid production caused by carbonic anhydrase inhibition; this defect (reduced flow) led to a net reflux of tracer into the ventricles. The reflux is believed to be due to the reduction of bulk cerebrospinal fluid from the ventricles.

Level of education and change in cognitive function in a community population of older persons.

In a community population of persons over the age of 65, cognitive function was assessed using brief performance tests on two occasions 3 years apart. Those with fewer years of formal education consistently had greater declines in cognitive function, independently of age, birthplace, language of interview, occupation, and income. These prospective findings suggest that low educational attainment or a correlate predicts cognitive decline. It is not clear, however, whether this relation represents a direct effect of education on future cognition, whether education might be related to occurrence of a disease leading to cognitive decline in older persons, or whether education might be a surrogate for some variable not included in the study.

Methodology for the differential diagnosis of a complex data set. A case study using data from routine CT scan examinations.

Data from routine CT scan examinations are employed to illustrate the use of the polychotomous logistic regression model as a statistical diagnostic tool. The assumptions of the model, the interpretation of its parameters, and its capabilities are described in detail. In carrying out the analysis on the CT data, a large, relatively sparse data set, many technical difficulties were encountered. Modifications to the methodology that were necessary to permit its implementation are described, and it is demonstrated that an unbiased analysis of T + 1 diagnostic categories can be implemented by separately performing T individual simple logistic analyses. The limitations of the methodology are discussed. It is hoped that this paper may serve as a basis for the practical implementation of the polychotomous logistic model in similar diagnostic settings.

Paired receiver operating characteristic curves and the effect of history on radiographic interpretation. CT of the head as a case study.

The use of a statistical technique for paired comparisons using receiver operating characteristic (ROC) curves is illustrated by studying the extent to which clinical history altered the interpretation of computed tomographic (CT) examinations of the head. Eighty-nine CT examinations of the head were presented in random order to four readers, first with minimum history (age and sex) and then several weeks later with complete neurological history as of the time the CT examination had been obtained. Using a paired ROC analysis, a small but significant (p less than .05) improvement was detected for the interpretations in the presence of complete history; for readings without history the average area was 94.4% and for readings with history it was 97.7%.

The clinical spectrum of hemorrhagic infarction.

The hospital records and head CT scans of 44 patients with hemorrhagic infarction were retrospectively analyzed. The majority of cases (73%) were embolic or possibly embolic in etiology, and 55% were not associated with anticoagulant therapy. Adverse prognosis was most clearly related to infarct size, underlying systemic illness, and symptomatic hemorrhage. Of the nineteen patients in whom serial CT scans documented conversion from bland to hemorrhagic infarction, 12 exhibited no clinical worsening at the time that hemorrhagic infarction was observed; the remaining seven, all of whom worsened, were receiving anticoagulant therapy at the time of documented conversion. Fourteen patients in whom anticoagulant therapy was used despite the findings of hemorrhagic infarction remained stable or improved during hospitalization.

Utilization of computed tomography of the head in a tertiary care hospital.

Data were prospectively collected on the signs, symptoms, and physical findings in 2,225 patients who underwent computed tomography (CT) of the head in a tertiary care teaching hospital. These data were correlated with the results of CT in an attempt to identify evidence of inappropriate utilization of diagnostic cranial CT. If only those patients had been examined whose presenting complaints were statistically more often seen in patients with abnormal CT studies than in those with normal CT studies, 26% of all examinations would have been eliminated, but 18% of all abnormal patients would have been missed. Similarly, if only those patients who were thought by their physicians to have a high likelihood of intracranial disease or to be diagnostic dilemmas had been examined, 34% of all examinations and 26% of all abnormal CT studies would have been eliminated. It is concluded that, in the setting studied here, there is no evidence of inappropriate utilization of cranial CT for diagnostic purposes.

Risk of death from Alzheimer's disease in a community population of older persons.

A random sample of 467 persons over age 65 years from the population of an urban US community, stratified by age, sex, and performance on a brief memory test, underwent clinical evaluation for dementing illness in 1982-1984. Of these persons, 134 had probable Alzheimer's disease, 166 had possible Alzheimer's disease, and 167 had no evidence of Alzheimer's disease. Over a median follow-up period of 4.9 years following evaluation, 165 (35%) died. Overall, persons with probable Alzheimer's disease had a relative risk of death 1.44 (95% confidence interval (Cl) 1.05-1.96) times that of the unaffected. Level of cognitive impairment and the presence of cachexia upon physical examination both strongly and independently modified risk of death. Among those with probable Alzheimer's disease, mortality for those with mild or moderate cognitive impairment and no evidence of cachexia was comparable to that of the unaffected. However, among those with probable Alzheimer's disease and either severe cognitive impairment or cachexia, the risk of death was substantially higher. Persons with probable Alzheimer's disease who had both severe cognitive impairment and clear cachexia had a risk of death 4.60 (95% Cl 1.63-13.1) times that of unaffected persons.

Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease.

Two brief screening tests, the Short Portable Mental Status Questionnaire (SPMSQ) and the East Boston Memory Test (EBMT), were included in a population questionnaire administered to 3,811 persons 65 years of age and older. A detailed clinical evaluation was then administered to 467 persons (drawn from high, medium and low performers on the EBMT) to determine who was cognitively impaired and the disorders that were responsible for that cognitive impairment. The results showed that the EBMT was better at enriching the population of the poor performance group with persons who had Alzheimer's disease (AD). It had a lower refusal rate among non-proxy respondents: 2% for the EMBT versus 9% for the SPMSQ. The sensitivity and positive predictive value were also higher for the EBMT than the SPMSQ when the diagnosis of interest was AD. However, there were persons with AD in all strata of performance on both the EBMT and the SPMSQ, emphasizing the importance of selecting persons from all performance strata in multistage community studies of AD.

Computed tomographic studies of the head in a teaching hospital and a community hospital: a comparison.

This investigation compared the use of computed tomography (CT) of the head at a large primary medical-school-affiliated hospital and at a large community hospital. There were two aims: first, to study the intrinsic characteristics of the patients in an attempt to determine the potential for developing accurate discrimination algorithms; and second, to study the patterns of neurodiagnostic tests used at these facilities. The results indicated that separability of patients into normal and abnormal categories at both institutions was extremely small. In addition, there was no significant difference in the numbers of types of ancillary tests used at both institutions. Overall, these data once more confirm the difficulty of altering CT usage patterns in primary or secondary hospitals without significantly affecting the number of abnormal patients identified.

Relation of smoking and alcohol consumption to incident Alzheimer's disease.

The authors examined the effects of smoking and alcohol use in a prospective community-based study of incident Alzheimer's disease. Two in-home interviews of the total elderly population of East Boston, Massachusetts, conducted in 1982 and 1985 were used to sample individuals for clinical evaluation for Alzheimer's disease. A total of 513 persons underwent detailed clinical evaluation including neurologic, neuropsychologic, and psychiatric evaluation to diagnose Alzheimer's disease. In weighted logistic regression controlled for age, sex, and education, the estimated odds ratio of Alzheimer's disease was 0.7 (95% confidence interval 0.3-1.4) for ever smokers compared with never smokers. For 40 pack-years of smoking, the odds ratio of Alzheimer's disease was 0.8 (95% confidence interval 0.6-1.1). Consumption of 1 oz (30 ml) of alcohol per day was associated with an odds ratio of 1.1 (95% confidence interval 0.8-1.5). These results suggest that recent mild-to-moderate consumption of alcohol is not substantially related to incidence of Alzheimer's disease and that smoking does not increase risk of the disease.

Age-specific incidence of Alzheimer's disease in a community population.

OBJECTIVE: To determine age-specific incidence rates of clinically diagnosed Alzheimer's disease. DESIGN: Cohort, followed a mean of 4.3 years. SETTING: East Boston, Mass. PARTICIPANTS: Of 2313 persons aged 65 years and older who were initially free of Alzheimer's disease, 1601 participated in the ascertainment of incident disease (80% of survivors), 409 declined participation, and 303 died before the end of the follow-up period. A stratified sample of 642 persons received detailed clinical evaluation. OUTCOME MEASURE: Diagnosis of new probable Alzheimer's disease through structured clinical evaluation including neurologic, neuropsychological, and psychiatric examination. Community incidence rates were computed by 5-year age groups, adjusted for gender, single year of age, length of follow-up interval, and sampling design. RESULTS: The estimated annual incidence of Alzheimer's disease in the population was 0.6% (95% confidence interval [CI], 0.3% to 0.9%) for persons aged 65 to 69 years, 1.0% (95% CI, 0.6% to 1.4%) for persons aged 70 to 74 years, 2.0% (95% CI, 1.3% to 2.7%) for persons aged 75 to 79 years, 3.3% (95% CI, 2.2% to 4.4%) for persons aged 80 to 84 years, and 8.4% (95% CI, 3.7% to 13.1%) for persons aged 85 years and older. CONCLUSIONS: The incidence of Alzheimer's disease is substantial and is approximately 14 times higher among persons older than 85 years compared with those between 65 and 69 years of age.

Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported.

Clinically diagnosed Alzheimer's disease and other dementing illnesses were assessed in a geographically defined US community. Of 3623 persons (80.8% of all community residents over 65 years of age) who had brief memory testing in their homes, a stratified sample of 467 persons underwent neurological, neuropsychological, and laboratory examination. Prevalence rates of Alzheimer's disease were calculated for the community population from the sample undergoing clinical evaluation. Of those over the age of 65 years, an estimated 10.3% (95% confidence limits, 8.1% and 12.5%) had probable Alzheimer's disease. This prevalence rate was strongly associated with age. Of those 65 to 74 years old, 3.0% (95% confidence limits, 0.8 and 5.2) had probable Alzheimer's disease, compared with 18.7% (95% confidence limits, 13.2 and 24.2) of those 75 to 84 years old and 47.2% (95% confidence limits, 37.0 and 63.2) of those over 85 years. Other dementing conditions were uncommon. Of community residents with moderate or severe cognitive impairment, 84.1% had clinically diagnosed Alzheimer's disease as the only probable diagnosis. These data suggest that clinically diagnosed Alzheimer's disease is a common condition and that its public health impact will continue to increase with increasing longevity of the population.

The effects of piracetam in children with dyslexia.

Following previous research which suggests that piracetam improves performance on tasks associated with the left hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in reading performance. Children were of at least normal intelligence, had normal findings on audiologic, ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor memory at baseline. It is suggested that longer term treatment with piracetam may result in additional improvements.