LETTER TO THE EDITOR Continued Concern About Nutritional Supplements and Cognitive Function in the Elderly To the Editor: We were interested to see the continued debate on Dr. Chandra’s article 1 concerning supplementation and cognitive function. We agree with the concerns raised by Roberts and Sternberg. 2 We did not reply to Dr. Chandra’s response 3 to our letter 4 as it is a convention that readers draw their own conclusions from a letter and the author’s reply to it. However, having been prompted to respond, we are still not satisfied that Dr. Chandra has answered our main point regarding the MMSE score. The MMSE reference he cites 5 —a placebo controlled trial in patients with moderately severe dementia— does not explain how his participants with a mean MMSE of 18 (+/- 3) can be con- sidered non-demented. Indeed, population-based norms of Amer- ican adults surveyed between 1980 and 1984 show a median MMSE score for adults aged 70 –74 of 28 if college educated, 27 if attended high school, 25 if reached eighth grade, and 22 if completed only fourth grade. 6 Therefore a mean score of 18 would be uncanny in a cognitively normal group of people aged over 65 from the middle socioeconomic class. It is conventional in medical practice to use a score of 24 as a “cut-off” below which further investigation into the cause of cognitive impairment would be required. 7 Dr. Chandra refers to the test in his letters as an “adapted MMSE” 3 and a “modified MMSE,” 8 but in the original article referenced the standard MMSE by Folstein et al. 9 We hope that this point can be clarified. Between our comments, and those of Roberts and Sternberg, there are unresolved concerns about Dr. Chandra’s data and re- sults. Clarity and explicitness are needed about the precise tests and procedures used in the study. Some of us belong to the American Psychological Association, which requires that authors in their journals make data available for possible re-analysis by fellow researchers for up to five years after publication. In the present case the proper course of action would be for Dr. Chandra to indicate a willingness to submit the data for analysis by other, impartial, researchers. Finally, we should emphasise that the concern expressed here is in part because of the astounding effect size of the results reported by Dr. Chandra. An improvement of 10 points in the MMSE (Table 2) 1 would in effect be a cure for dementia in many people, comparing with a typical mean response of 1.84 MMSE points (95% CI, 0.53 to 3.15) for the best available treatment at present (donepezil, a cholinesterase inhibitor). 10 If his findings are correct, Dr. Chandra has reported one of the most efficacious treatments effects in medicine since the introduction of penicillin; this in turn would suggest that millions of cognitively-impaired patients around the world would achieve huge improvements in cognitive function with a cheap, safe treatment. It therefore behooves the research community to establish whether the reported effect is scientifically valid, and we would urge Dr. Chandra (1) to clarify the cognitive tests and procedures used, and (2) to indicate that the data are available for re-analysis. Susan D. Shenkin, MBChB Martha C. Whiteman, PhD Alison Pattie, BSc Ian J. Deary, PhD Department of Psychology University of Edinburgh Edinburgh, UK REFERENCES 1. Chandra RK. Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects. Nutrition 2001;17:709 2. Roberts S, Sternberg S. Do nutritional supplements improve cognitive function in the elderly? Nutrition 2003;19:976 3. Chandra RK. Response to the comments of Shenkin et al. Nutrition 2002;18:364 4. Shenkin SD, Whiteman MC, Pattie A, Deary IJ. Supplementation and the elderly: dramatic results? Nutrition 2002;18:364 5. Sano M, Ernesto C, Thomas RG. A controlled trial of selegiline, alphatocopherol or both as treatment for Alzheimer’s disease. N Engl J Med 1997;336:1216 6. Crum RM, Anthony JC, BAssett SS, Folstein MF. Population-based norms for the Mini-Mental State Examination by age and education level. JAMA 1993; 269(18):2386 7. Tallis RC, Fillit HM, Brocklehurst JC, eds. Brocklehurst’s textbook of geriatric medicine and gerontology, 5th ed. New York: Churchill Livingstone, 1998 8. Chandra RK. Can nutrient supplements improve functional outcome in the elderly? Nutrition 2003;19:978 9. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189 10. Birks JS, Harvey R. Donepezil for dementia due to Alzheimer’s disease. Coch- rane Database of Systematic Reviews. 2003;3:CD001190 doi:10.1016/j.nut.2003.12.002 Correspondence to: Dr Susan Shenkin, Department of Psychology, Uni- versity of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, United Kingdom. E-mail: Susan.Shenkin@ed.ac.uk 0899-9007/04/$30.00 Nutrition 20:336, 2004 ©Elsevier Inc., 2004. Printed in the United States. All rights reserved.