Cognitive Function Improvement info from Edge

Here is an excerpt from an email I received from Constantine/Edge on behalf of another patient just starting chemo and worried about losing cognitive function. They have just begun taking the supplement (not the prescription drugs) so I don't even have anecdotal results to present. For anyone who's interested: 

Cholinesterase inhibitors (ChEIs)

(Acetyl)cholinesterase inhibitor agents are primarily used in treating Alzheimer's Disease (AD) and various forms of dementia, and include donepezil (Aricept), rivastigmine (Exelon), and galantamine (the prescription agent Razadyne, formerly Reminyl). Tim Ahles with Center for Psycho-Oncology Research at Dartmouth has provided preliminary evidence that individuals who carry the mutation represented by the e4 allele of the apolipoprotein E (APOE) gene implicated in Alzheimer's disease may be more vulnerable to chemo-related cognitive decline as well as increased vulnerability for cognitive problems from other types of trauma (his earlier study in 2003 had already shown that about 21 percent of breast cancer or lymphoma survivors carry at least one e4 allele). These insights have led Eduardo Bruera and his MD Anderson team to evaluate donepezil's anti-fatigue benefits in cancer patients, with positive results from the open-label pilot study reported at ASCO 2003.
[I note here that his later negative results just reported at ASCO 2007 claiming to find that donepezil was not superior to placebo in the treatment of cancer-related fatigue are not to be taken as counter-evidence: in my own critical appraisal of the ASCO 2007 study, I exposed the two fatal methodological compromises of the study, namely (1) that donepezil was dosed at 5 mg daily, almost certainly a sub-therapeutic level and against the standard 10mg/d schedule, and (2) assessments were made after only 1 week on the active agent - it is patently unreasonable to expect a persistent/chronic symptom such as fatigue to respond after a mere week of any therapy, and this is in contrast to what was already established by Edward Shaw at the Brain Tumor Center of Excellence at Wake Forest University, who found significant improvement in cognitive functioning (and also in mood, and health-related QoL) in irradiated brain tumor patients using donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks, followed by a washout period of 6 weeks offdrug, thus deploying the motivated therapeutic 10mg dose for an 18 week duration.]

And although the available studies have used the prescription cholinesterase inhibitor agent donepezil (Aricept), one would expect, given the shared underlying mechanisms, that efficacy would incur also to another ChEI agent like galantamine, which is also available as a nonprescription standardized herbal product). Hence a trial of
the pharmaceutical grade of the over-the-counter form Galantamind, available from iHerb.com at:
http://www.iherb.com/store/ProductDetails.aspx?c=Herbs&pid=LEM-01680
may be worthwhile, starting at 8mg. once day for one week, then escalating to two daily (16mg) thereafter (best taken towards end of a meal, preferably as late as possible in the day, with last meal).

Saluki, here's the abstract from that paper.  The washout period at the end enabled the scientists to get a final data point. After seeing improvement at baseline, 12 weeks and 24 weeks, the final data point might indicate whether the improvement persisted or declined without the drug. The authors indicate there was a decline in the measured functions, but that the amount of decline was not statistically significant. 

This was a prospective study and a control group was not used. This would have  shown whether the improvement was related to the Aricept or would have occurred naturally. The conclusion in the abstract indicates a double blind, placebo-controlled phase III trial is being planned. 

http://www.ncbi.nlm.nih.gov/sites/entrez

Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life.

Shaw EG, Rosdhal R, D'Agostino RB Jr, Lovato J, Naughton MJ, Robbins ME, Rapp SR.

Department of Radiation Oncology, Wake Forest University School of Medicine, Brain Tumor Center of Excellence of WFU, Winston-Salem, NC 27157-1030, USA. eshaw@wfubmc.edu

PURPOSE: A prospective, open-label phase II study was conducted to determine whether donepezil, a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer's type dementia, improved cognitive functioning, mood, and quality of life (QOL) in irradiated brain tumor patients. PATIENTS AND METHODS: Thirty-four patients received donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks, followed by a washout period of 6 weeks off drug. Outcomes were assessed at baseline, 12, 24 (end of treatment), and 30 weeks (end of wash-out). All tests were administered by a trained research nurse. RESULTS: Of 35 patients who initiated the study, 24 patients (mean age, 45 years) remained on study for 24 weeks and completed all outcome assessments. All 24 patients had a primary brain tumor, mostly low-grade glioma. Scores significantly improved between baseline (pretreatment) and week 24 on measures of attention/concentration, verbal memory, and figural memory and a trend for verbal fluency (all P < .05). Confused mood also improved from baseline to 24 weeks (P = .004), with a trend for fatigue and anger (all P < .05). Health-related QOL improved significantly from baseline to 24 weeks, particularly, for brain specific concerns with a trend for improvement in emotional and social functioning (all P < .05). CONCLUSION: Cognitive functioning, mood, and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil. Toxicities were minimal. We are planning a double blinded, placebo-controlled, phase III trial of donepezil to confirm these favorable results.

PMID: 16549835 [PubMed - indexed for MEDLINE]