Neurology -- Correspondence for Knopman et al., 65 (7) 986-990

Correspondence published:

Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease: Martin M Bednar, MD, PhD, TA Lee, PharmD, PhD, B Wolozin, MD, PhD, KB Weiss, MD, MPH (21 February 2006)

Reply from the Authors: David S. Knopman, Walter A. Rocca (21 February 2006)

Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease 21 February 2006

Martin M Bednar, MD, PhD,
Pfizer Inc.
Eastern Point Road, 8260-2604, Groton, CT 06340,
TA Lee, PharmD, PhD, B Wolozin, MD, PhD, KB Weiss, MD, MPH
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Re: Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease

martin.m.bednar{at}pfizer.com Martin M Bednar, MD, PhD, et al.

We read with interest the recent articles by Knopman, et al [1] and McKhann et al [2] examining the possible relationship of coronary artery bypass surgery (CABG) and the subsequent emergence of Alzheimer Disease (AD). Our group has also recently published on the issue of AD incidence following CABG surgery [3] and see this forum as an opportunity to discuss these results, especially in light of our conclusion that CABG surgery is associated with the early emergence of AD.
In our study, we retrospectively followed a large VA cohort for up to six years after either CABG surgery (N=5,216) or percutaneous transluminal coronary angioplasty (PTCA; N=3,954), noting an adjusted risk of AD associated with CABG versus PTCA of 1.71 (95% CI, 1.02-2.87; p = 0.04). We did not observe separation of the two groups until greater than three years following the procedure. Thus, it is not surprising that the study by McKhann et al, as well as an earlier study by Newman et al [4], did not reveal any evidence for cognitive decline at up to one year of follow- up. However, it is notable that Newman�s study did observe evidence of cognitive decline five years post CABG.
The study by Knopman et al, while well designed and having a longer follow-up period, still represents a relatively small sample size with only 34 cases of AD noted. The wide 95% CIs just barely exclude the OR that we observed in our study (1.56 vs. 1.71), although we acknowledge their point estimate is 0.78. It is likely that the two populations studied differ in baseline co-morbidities, with the VA cohort possibly being a sicker population at the time of their procedure. A difference in the cohorts� health status at baseline could have contributed to the incongruent outcomes observed between our study and Knopman�s study.
As we have discussed in our report, we acknowledge a number of weaknesses in our study design, but we are concerned that the short time frame and low statistical power of the current studies could provide a misleading assessment of the impact of CABG surgery on the emergence of AD.
Disclosures: Dr. Ben Wolozin: Received honoraria from the sponsor during the conduct of the study (< 10,000 per year) Dr. Todd Lee: Received a grant from the same sponsor for other research or activities not reported in this research (research grant for a COPD project, > 10,000/year). Dr. Kevin Weiss: nothing to disclose

Reply from the Authors 21 February 2006

David S. Knopman,
Department of Neurology
Mayo Clinic, 200 First Street SW, Rochester, MN 55905,
Walter A. Rocca
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Re: Reply from the Authors

knopman{at}mayo.edu David S. Knopman, et al.

We appreciate the interest by Bednar et al in our study and we restricted our reply to the comments pertinent to our results. Our study [1] examined the long-term effects of CABG surgery on the brain by identifying incident cases of dementia in a geographically defined population.
We matched our dementia cases to non- demented controls of the same age (� 1 year) and sex drawn from the same community. Our study had a longer time frame compared to that of Lee et al, [3] with a median lag time between CABG and dementia of 5.5 years (range = 0.1 to 15.9). We found no differences between cases and controls in the frequency of preceding CABG surgery.
We acknowledged in our paper that we could not exclude a small association; however, our results showed no trend in the direction of a risk for dementia after CABG.[1] Our case- control methodology avoided the difficulty of identifying a suitable reference group for a cohort study. Short of using a traditional randomized clinical trial, it is impossible to prevent a difference in severity of cardiovascular disease between patients with CABG and referent subjects (confounding by indication). [5]
Lee et al's comparison group included persons who underwent percutaneous transluminal coronary angioplasty (PTCA) because they had a less severe form of vascular disease than the subjects who underwent CABG surgery.[3] For example, their PTCA patients were younger, had far shorter lengths of hospitalization following the surgery (6.5 vs. 11.9 days) and far fewer hospitalization days prior to the surgery (1.4 vs. 4.5 days) than the CABG patients. Five or more diagnoses were associated with the index hospitalization in 59% of the PTCA patients versus 63% of the CABG patients.
Constructing a suitable comparison group for people undergoing CABG surgery has greatly hampered analysis of the long-term effects of CABG. Thus, it can be argued that the difference in rate of dementia observed by Lee et al reflected the severity of the underlying cardiovascular disease in the two arms of the cohort study rather than the effect of CABG surgery itself on the brain.
References
References
1. Knopman DS, Petersen RC, Cha RH, Edland SD, Rocca WA. Coronary Artery Bypass Grafting is not a Risk Factor for Dementia or Alzheimer Disease. Neurology 2005; 65:986-990.
2. McKhann GM, Grega, MA, Borowicz LM et al. Is there Cognitive Decline 1 Year after CABG? Neurology 2005; 65:991-999.
3. Lee TA, Wolozin B, Weiss KB, Bednar MM. Assessment of the Emergence of Alzheimer�s Disease Following Coronary Artery Bypass Graft Surgery or Percutaneous Transluminal Coronary Angioplasty. J. Alzheimer Disease 2005; 7:319-324.
4. Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal Assessment of Neurocognitive Function after Coronary-Artery Bypass Surgery. The New England Journal of Medicine 2001; 344:395-402.
5. Szklo M, Nieto FJ. Epidemiology. Beyond the Basics. Gaithersburg: Aspen Publishers, Inc. 2000.
Disclosure: The authors report no conflicts of interest.