Clinical Briefs
By Louis Kuritzky, MD
Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment
Mild cognitive impairment (mci) is a term used to designate a level of cognitive change in between normalcy and dementia. Alzheimer’s disease (ALZ) continues to be an individually and epidemiologically compelling disorder, with only modest therapeutic advances in the previous decade. ALZ might be preventable, and an appropriate high-risk population to study would be subjects with MCI, amongst whom as many as 10-15% per year progress to ALZ.
Based upon the hypothesis that oxidative damage might contribute to ALZ, and that cholinesterase inhibition has shown some symptomatic improvement in ALZ, both agents were considered of merit for intervention in MCI patients. In a randomized, double blind fashion, subjects (n = 769) were assigned to vitamin E (2000 IU/d), donepezil 10 mg/d, or placebo. The primary end point, assessed by intention-to-treat analysis, was development of ALZ (possible or probable).
Over the 3-year study period, there was no demonstrable difference between either Vitamin E, donepezil, or placebo. At an early assessment point (12 months) the donepezil group demonstrated reduced ALZ development, but this improvement was not sustained to the end of the trial. Neither Vitamin E nor donepezil appears effective over the long term (3 years) in forestalling ALZ amongst individuals with MCI.
Petersen RC, et al N Engl J Med. 2005;352:2379-2388.
Foot Small Muscle Atrophy Before the Detection of Clinical Neuropathy
Diabetic peripheral neuropathy (DPN) is costly to diabetics in that it is associated with subsequent disability and limb loss, not to mention the frequently problematic neuropathic pain. Small muscle atrophy (SMA) is felt to be a primary contributor to derangements in musculoligamentous foot mechanics which foster structural changes (eg, clawing of the toes. Ultimately, the combination of insensitivity from sensory neuropathy, SMA, and alteration of foot mechanics conspire to induce foot ulcers.
MRI scanning can be used to quantify phosphorus metabolism in muscle. Healthy muscles subjected to ischemia quickly restore phosphorus metabolism to normal, whereas unhealthy muscle does not. Greenman and colleagues studied a population of non-diabetics, diabetics with DPN, and diabetics without DPN to evaluate the use of MRI-phosphorus scanning.
Subjects with DPN were identified using typical tools such as a biothesiometer for vibration perception threshold and Semmes-Weinstein monofilament testing.
MRI-phosphorus testing indicated a statistically significant lower level of viable muscle tissue in the feet of DPN patients than diabetics without DPN. However, even diabetics without DPN demonstrated reductions in muscle tissue compared with normal controls. These data indicate that SMA is occurring prior to the advent of overt DPN in diabetics, and becomes more progressive as DPN becomes evident.
Greenman RL, et al. Diabetes Care. 2005;28:1425-1430.
Statins and the Risk of Colorectal Cancer
Nsaids have shown convincing benefits for prevention of colon cancer (CCA) in high-risk populations. The toxicity of NSAIDs, including GI bleeding and cardiovascular events, has recently been highlighted and includes the here-to-fore-considered safer’ COXIBs. Hence the search for additional CCA chemopreventive agents continues. Statins have theoretic potential benefits for CCA since HMG-CoA reductase (the enzyme upon which statins impact) is overexpressed by CCA cells, and in vitro data support increased CCA cell apoptosis stimulation by statins.
To evaluate potential benefits from statin therapy, a population from the Molecular Epidemiology of Colorectal Cancer study (n = 1,953) was studied using a case-control method. Participants had received a diagnosis of CCA between 1998-2004, vs their case controls, who did not have a diagnosis of CCA.
Use of statins for at least 5 years was associated with a 0.5 odds ratio for CCA risk (approximately 47% relative risk reduction). Contributing to the evidence that the statin effect is class specific, use of fibrates in this same population was not associated with reduced risk. Poynter et al suggest that the role of statins in CCA chemoprevention is worthy of further study. A large prospective interventional trial would be ideal.
Poynter JN, et al. N Engl J Med. 2005;352:2184-2192.
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