Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Double-blind placebo-controlled study of velnacrine in Alzheimer's disease.

The present study assessed the safety and efficacy of the cholinesterase inhibitor, velnacrine, for treating the cognitive symptoms of Alzheimer's disease. Patients (N = 236) meeting NINCDS-ADRDA criteria for Alzheimer's disease entered a double-blind, placebo-controlled dose-ranging protocol (30, 75, 150, 225 mg/day each for one week) to identify velnacrine responders (> or = four point improvement on the cognitive subscale of the Alzheimer's Disease Assessment Scale [ADAScog]). After a two week drug washout, velnacrine responders were randomly assigned to their best velnacrine dose or placebo in a six week dose-replication protocol employing the ADAScog and the Clinical Global Improvement scale as primary outcome measures. During dose-replication, intent-to-treat analysis revealed that velnacrine patients scored significantly better than placebo patients on the ADAScog after two (p < 0.004), four (p < 0.025) and six (p < 0.001) weeks of treatment. No significant treatment effect on Clinical Global Improvement scores was observed. The primary adverse event was an asymptomatic elevation of liver transaminases found among 28% of the 236 treated patients. Cholinergic side effects including diarrhea (14%), nausea (11%) and vomiting (5%) were observed and 8% of patients experienced skin rash. The present study identified a subgroup of Alzheimer's patients who demonstrated a significant, but modest, improvement during velnacrine treatment on structured cognitive testing.

Infections other than AIDS.

Neurologic manifestations of severe infectious complications of drug abuse and chronic alcoholism are reviewed in this article. Portals of entry from cutaneous postinjection infections and multiple vascular injection sites may lead to pyomyositis, tetanus, infective endocarditis, meningitis, brain abscesses, and vertebral osteomyelitis. Chronic intranasal abuse of cocaine may be followed by frontal osteomyelitis, botulism, brain abscess, and visual loss. Problems of hepatitis, malaria, and syphilis in drug abusers are discussed also.

The Harlem regional stroke program: an overview.

The Harlem regional stroke program has been a demonstration model designed to detect, treat, and follow up stroke and hypertension patients through collaboration with a municipal teaching hospital, community practitioners, local service organizations and a major medical school. Many aspects of the stroke program appear suitable for replication at the local or regional levels in varied settings. In particular, the program has demonstrated the need to link community outreach programs, stressing early detection and preventive-care education, with sustained treatment and follow-up programs. The stroke program has also suggested ways in which specialized programs can be incorporated into long-term comprehensive health planning and care facilities at local and regional levels.

Frequency and course of pure motor hemiparesis: a clinical study.

A review of 850 acute unselected stroke cases at Harlem Hospital found only 25 (3%) who met a clinical definition of pure motor hemiparesis. Compared to other cerebral infarction survivors, the 23 pure motor syndrome survivors were slightly younger, not much more often hypertensive and did not make a faster recovery. The degree of motor deficit a year later was nearly the same in both groups. Brain scans were positive in one-third of the pure motor patients, which suggests that this clinical picture may be associated with larger brain lesions than had been suspected before, as well as with lacunar infarction.

Neuronal depletion in the globus pallidus of heroin addicts.

Decreased neuronal population densities are described in the globus pallidus of narcotic addicts. Toxicologic studies indicate mixed addiction to be frequent, but exposure to parenteral heroin is the only common factor. This permanent brain damage seems more likely to be caused by recurrent episodes of hypoxia during severe reactions to narcotics than to be related to direct neurotoxic effects of heroin. The lesion may account for some of the long term changes observed in addicts.

Aphasia in acute stroke.

Previous surveys of stroke populations have offered only cursory information on language disturbance, and, conversely, few surveys of aphasic populations have dealth exclusively with stroke or with acute phenomena. This paper describes aphasia in 850 acute stroke patients consecutively registered by the Harlem Regional Stroke Program, of whom 177 (21%) were aphasic; of these, nine were of Broca's type, 24 were of Wernicke's type, 14 were of anomic, ten were conduction, seven were of "isolation" type, and 107 were "mixed." An unexpected finding was a significant over-representation of men among the nonfluent aphasics. During the following four to 12 weeks, 12% of fluent aphasics died, and 12% remained moderately or severely impaired; among survivors, aphasia improved in 74%, and in 44% it cleared completely. During the same period, 32% of nonfluent aphasics died, and 34% remained moderately or severely impaired; among survivors, aphasia improved in 52%, and in only 13% did it clear completely. In both fluent and nonfluent groups, hemiparesis and/or visual field cut were associated with poor prognosis.

Stroke associated with addiction to heroin.

During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke.