A Trial of Lipotropic Enzymes in Atheromatous ("Arteriosclerotic") Dementia

Abstract

&dquo;Strokes&dquo; due to cerebrovascular disease account for nearly one-fifth of all present deaths, compared with 9 per cent of all deaths in 1935,~ and the mortality and morbidity continue to rise.The etiology of atheroma is in dispute, but it has been suggested that ischemia of the middle zone of the arterial walls caused by intimal thickening leads to loss of oxidative enzymes, with consequent accumulation of cholesterol and other fats in the inner zone of the arterial ~=a11.2 Abnormally low values of various enzymes, principally dehydrogenases, have been found in atheromatous artery walls,3 whereas the activity of aldolase is apparently decreased in sclerotic parts of the aortic wall and increased in normal parts of the same aorta.4 Diminution of adenosine triphosphatase activity is said to precede the development of any observable anatomic change.5 There have therefore been several attempts to treat atheroma with various enzymes including j3glueuronidase,&dquo; cytochrome c7 and hepatic catalases as well as with such substances as nicotinic acid,9 metal ionsl° and estrogens, which may well act enzymatically.ll The subject is well reviewed by Kask.11 The enzyme preparation used here has been reported to be successful in atheroma by many authors, some listed here.~2-2o Although these trials were uncontrolled, large numbers (e.g., Forster21 had 2187) of patients were used and often objective criteria of improvement, e.g., skin reddening time, 22 the elasticity coefficient of vascular walls23 and pulse wave velocity.l2 Cerebral atheroma patients may do particularly well.19, 24, 25 Animal studies indicate the prevention and remission of experimental atheroma in rats and dogs26 and in rabbits27 under controlled conditions as well as successful veterinary use28 and we felt that a controlled trial in human cerebral atheroma would be of interest. METHODA. Case selection, grading and randomization. Patients were considered to have clinical atheromatous dementia if they showed objective signs of dementia for at least 6 months plus at least three of the following eight clinical criteria, which are generally regarded as constituting the clinical syndrome.29-31 Hypertension (180/100 mm Hg or over) ; focal neurologic signs; a history of stroke or recent fits; emotional lability or depression; preservation of basic personality ; confusion worse at night; a fluctuating course; retinal or brachial arterial sclerosis.Forty-nine patients meeting these criteria were collected from our hospital at The University of Iowa Libraries on May 31, 2015 ang.sagepub.com Downloaded from 288 practice, an average of about 5.5 criteria being present in each case. (We were able to perform a postmortem examination in 9 of the 12 patients who died during or since the trial, and the diagnosis was confirmed in 8 of the 9.) The trial was explained to each patient and their nearest relative as much as possible ; they also consented to the use of placebo. All mentally accessible patients and relatives consented, but the relatives of one severel...