Neurology -- Correspondence for Abbott et al., 57 (3) 456-462

Correspondence published:

Reply to Dr. Lesser's letter: R D Abbott, "H Petrovitch, L R White, G W Ross" (6 November 2001)

Frequency of bowel movements and the future risk of Parkinson’s disease: Gerson T Lesser (6 November 2001)

Reply to Dr. Lesser's letter 6 November 2001

R D Abbott
University of Virginia School of Medicine Charlottesville VA,
"H Petrovitch, L R White, G W Ross"
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Re: Reply to Dr. Lesser's letter

rda3e{at}virginia.edu R D Abbott, et al.

While further explanation is needed, the long interval between reported constipation and the diagnosis of Parkinson’s disease (PD) in our study may provide some insights into the pathogenesis of PD and related histologic changes beginning as early as age 25. [2] Dr. Lesser speculates that infrequent bowel movements might allow neurotoxins greater access to the central nervous system, and that cumulative exposure to certain neurotoxins at low levels over many years might explain the association we observed. While this is an important possibility, one argument against this is that rates of PD seem to be slightly lower in women, even though bowel movement frequency is greater in men. [3].
We favor the idea that some persons may be at increased risk for the development of PD by virtue of a life-long paucity of sympathetic and dopaminergic neural reserves, manifested by constipation as a constitutional gastrointestinal characteristic, and by a lowering of thresholds for the appearance of PD as neurons are lost from the substantia nigra, regardless of the cause of such losses.
We agree with the second observation of Dr. Lesser, as we also note in our paper [1], that there may be underlying environmental factors that can impact the risk of PD. Like many chronic diseases that appear in later life, it is likely that both constitutional and environmental factors contribute to an increased risk of disease. While this may be discouraging to persons hoping to prevent disease with a single intervention, the more realistic view is that strategy for prevention (such as avoiding exogenous neurotoxins) may ultimately be most important and most effective in persons whose risk begins at a high level because of a genetic or constitutional susceptibility.
References:
1. Abbott RD, Petrovitch H, White LR, et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001;57:456-462.
2. Gibb WRG, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1988;51:745-752.
3. Everhart JE, Go VLW, Johannes RS, Fitzsimmons SC, Roth HP, White LR. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989;34:1153-1162.

Frequency of bowel movements and the future risk of Parkinson’s disease 6 November 2001

Gerson T Lesser
The Jewish Home and Hospital New York
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Re: Frequency of bowel movements and the future risk of Parkinson’s disease

glesser{at}jhha.org Gerson T Lesser

Abbott et al. [1] have collected unique longitudinal information relating a less frequent bowel habit to greater risk for future Parkinson’s disease (PD). However, it is difficult to accept the conclusion that this manifestation of PD (constipation) predates the motor symptoms by so many years. Furthermore, since a particular individual’s bowel habit tends to remain nearly constant through adult life, one must assume that the bowel habits of the great majority of those recorded in 1971-1974 had already been “in place” for many years, probably decades. The present findings support this assumption, as intra-individual bowel movements were significantly correlated 20+ years apart. [1] Using this assumption, one can extend the average 12-year interval (observed from 1971-74) from “onset” of constipation to the clinical diagnosis of PD by perhaps two decades and, more reasonably, estimate this interval to be some 25-35 years. From various sources of information, the latency period of presymptomatic PD neurodegeneration has been projected to be as long as 20 years, or as short as <5 years. [2] Even if one accepts and extends the longest of these estimates, an average interval of 25-35 years between an early manifestation of PD (constipation) and the appearance of clinical motor disease seems highly unlikely.
However, a more plausible hypothesis can be advanced to explain the important observations of Abbott et al. [1] It has always been considered that some environmental offender, alone or in various combinations, and perhaps only in susceptible individuals, may damage nigral cells; among those more recently advanced have been manganese or other heavy metals, combinations of metals, herbicides and organochlorine insecticides, [3] and various isoquinoline derivatives structurally related to MPTP. [4] Although enteral absorption and handling of various substances is exceedingly complex, [5] it seems logical that, over years, ingested substances with limited absorption would enter the bloodstream to a greater extent in those with slower intestinal transit. With such an hypothesis, the longer the existence of an infrequent bowel habit the more likely would a susceptible individual absorb sufficient “toxin” to effect the major neruodegeneration leading to full-blown PD.
Another observation of the present authors lends some support to underlying environmental factors in development of PD. [1] It appears that, in their Asian homelands, Orientals have lower prevalence of PD than European or U.S. Caucasians. However, the present report found the prevalence of PD in this cohort of Japanese ancestry living in the U.S. to be approximately the same as that of European or U.S. Caucasians.
References:
1. Abbott RD, Petrovitch H, White LR, et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001;57:456-462.
2. Veldman BAJ, Wijn AM, Knoers N, Praamstra P, Horstink MWIM. Genetic and environmental risk factors in Parkinson’s disease. Clin Neurol Neurosurg 1998;100:15-26.
3. Corrigan FM, Wienburg CL, Shore RF, Daniel SE, Mann D. Organochlorine insecticides in substantia nigra in Parkinson’s disease. J Toxicol Env Health Part A 2000;59:229-234.
4. McNaught KS, Carrupt PA, Altomare C, et al. Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson’s disease. Biochem Pharmacol 1998;56:921-933.
5. Diamond GL, Goodrum PE, Felter SP, Ruoff WL. Gastrointestinal absorption of metals. Drug & Chemical Toxicology 1998;21:223-251.