Biomedical subjects
Publications and source records attributed to L A Hershey.
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It has been suggested that dietary antioxidants reduce Parkinson's disease (PD) risk by neutralizing free radicals, thus preventing injury to neurons in the substantia nigra. This case-control study examined the possible role of long-term dietary antioxidant intake in PD etiology. Cases (n = 57) were males 45-79 years old with at least two cardinal signs of PD and no evidence of other forms of parkinsonism or dementia. Age-matched friend controls (n = 50) were chosen from lists provided by the cases. Usual dietary intake 20 years ago, including vitamins E and C and carotenoids, was assessed by a 102-item food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression. Antioxidant intake, adjusted for age, education, smoking, rural living, and total energy intake, was not associated with reduced PD risk. Trends toward greater PD risk were associated with higher intakes of vitamin C and carotenoids, especially xanthophylls, reflecting higher intakes by PD cases of fruit and certain vegetables. Intakes of sweet foods, including fruit, were associated with higher PD risk, suggesting that the observed trends may be due to a preference for sweet foods. This study does not provide support for a protective effect of long-term dietary antioxidant intake on PD risk.
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Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.
OBJECTIVE: To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. DESIGN: A 12-week, double-blind, placebo-controlled, parallel-group study. SETTING: Outpatients at 23 centers. PATIENTS: Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. INTERVENTIONS: In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). RESULTS: Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P = .014), clinician-rated CGIC (P = .014), and caregiver-rated CGIC (P = .006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P = .015), clinician-rated CGIC (P = .016), and caregiver-rated CGIC (P = .028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). CONCLUSIONS: These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations.
OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.
We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.
Stroke is the third leading cause of death in North America. Most studies indicate that women are just as likely as men to have an initial stroke but less likely to have a recurrent stroke. Aspirin and ticlopidine are two antiplatelet drugs that reduce the risk of recurrent stroke by 25% to 30%. In some stroke prevention trials, aspirin has been shown to be more effective for men than for women. In contrast, major stroke prevention trials using ticlopidine have demonstrated equal benefit in women and in men. The overall incidence of adverse effects seen with ticlopidine is not significantly different from that observed with aspirin. There are now two effective agents useful in stroke prevention in both men and women.
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Depression and suicide are significant problems in the elderly, both in terms of their severity and their prevalence. It is particularly difficult to distinguish depression from early dementia, since elderly depressed patients often deny mood disorder and focus on their memory problems. This differential diagnostic dilemma is further complicated by the fact that 20 percent of Alzheimer-type dementia patients have moderate to severe depression. An even higher prevalence of depression can be seen in elderly patients with stroke or Parkinson's disease. Most all of the depressive disorders of the elderly are amenable to one form or combination of therapies: pharmacologic, electro-convulsive, or psychotherapy. Tricyclic antidepressants are often associated with adverse drug reactions in the elderly, so alternatives such as MAO inhibitors, alprazolam, bupropion and psychostimulants are currently being explored in this patient population.
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Patients with vascular dementia show distinctive white matter lesions on MRI. We performed MRI on 34 patients with documented ischemic cerebrovascular disease to see whether demented and nondemented patients differ with respect to enlarged CSF spaces or white matter lesions. All eight demented patients had white matter lesions on MRI, just as did many borderline and nondemented patients. Enlargement of central CSF spaces was the only radiographic feature that was seen more commonly in demented than in nondemented patients with ischemic cerebrovascular disease.
Vascular dementia is a common and potentially reversible type of dementing illness. Simple, yet valid, assessment instruments are needed to quantitate the severity of cognitive and functional impairment in vascular dementia patients seen in consultation or studied in therapeutic trails. Among sixty-three patients with known ischemic cerebrovascular disease, we found thirteen who satisfied research criteria for vascular dementia, nineteen who were "borderline" and thirty-one who were not demented. We administered the Cognitive Capacity Screening Examination and the Functional Activities Questionnaire to these patients and found both tests capable of distinguishing demented from nondemented groups with a high degree of sensitivity and specificity. This battery of assessment instruments was especially helpful in evaluating patients who fell into the "borderline" category. Both tests can be easily administered at the bedside or during routine office visits.
The clinical course of vascular dementia has been described as a stepwise deterioration over time. We studied the chronologic course of cognitive performance over 1-4 years in seven patients with known ischemic cerebrovascular disease whose dementia subtype was assigned according to the clinical history and the pattern of white matter lesions seen on magnetic resonance imaging (MRI). One patient had the lacunar state, three had subcortical arteriosclerotic encephalopathy and three had multiple cortical and subcortical strokes. All were being treated with an antiplatelet agent and six received antihypertensive therapy. Four of the seven vascular dementia patients improved cognitively over the first year. A fluctuating course was eventually seen in all patients. None showed stepwise deterioration of cognitive function over time. The MRI was useful in subclassifying vascular dementia patients, but the clinical course did not appear to vary as a function of the dementia subtype.
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Explore the source record for details and available documents.