Identical Twins Show Survival Gap When Only One Has Parkinson's, Ten-Year Study Finds

Of the 54 pairs of twins enrolled in an Italian study, in which one twin had Parkinson's disease and the other did not, 17 of the affected twins had died by the end of ten years. Only three of their unaffected co-twins had. That gap, 31.5 percent against 5.6 percent, is the central finding of a long-term follow-up published in the journal Brain Sciences.

The design is the point. Twins share an intrauterine environment, early nutrition and much of their socioeconomic background. Identical twins also share all of their genetic material, while fraternal twins share about half. Pairs in which only one twin develops Parkinson's give researchers a way to look at non-genetic influences on the disease. Long-term follow-up of such pairs has been scarce, which is what this study set out to address.

The researchers recruited the pairs in Italy. In each, one twin met the criteria for Parkinson's and the other had no neurodegenerative disease. Zygosity was settled by microsatellite analysis. At baseline, questionnaires covered smoking, disease duration, gastrointestinal symptoms, levodopa dose and other illnesses, and a food frequency questionnaire captured diet. Ten years on, the team determined who had survived and re-checked whether each pair was still discordant. They also ran telephone interviews to update the data and to ask retrospectively about lifetime exposure to herbicides, pesticides, heavy metals and organic solvents. Mortality was the primary endpoint; diet, clinical features and nutrition were secondary.

The cohort totaled 108 people, 26 identical pairs and 28 fraternal pairs, with an average age of 66. At follow-up, 33 pairs were alive, still discordant and reassessed. Those pairs were younger, and their affected members had shorter disease duration and lower baseline levodopa doses than the pairs lost along the way, which may have shaped the later comparisons.

Among identical twins there were nine deaths, and every one was in the twin with Parkinson's. Among fraternal pairs, eight affected twins and three unaffected co-twins died. Causes in affected twins included complications of neurodegenerative disease, cardiovascular events, COVID-19, cancer and other or unspecified causes. Of the three unaffected twins who died, two had unspecified causes and one died of cancer. Survival curves for the two groups diverged significantly over time, more sharply among identical twins, though the small number of deaths leaves the size of that difference uncertain. The authors read the identical-twin result as a sign that shared genes alone cannot explain the excess mortality.

The clinical picture was more mixed. Levodopa doses and disease duration rose over the decade. Constipation was significantly more common in affected twins at baseline and again at follow-up, and regular bowel habits were less common among them, a gap that widened while unaffected twins showed no significant change. Other illnesses did not differ within pairs at baseline. Hypertension looked more frequent in unaffected co-twins at follow-up, but not significantly. Body weight and BMI showed no significant differences at either point, though follow-up weight was self-reported.

Diet differed little. Affected twins ate less fish at both time points, but only the follow-up difference held after correction within the dietary category, and it vanished in identical twins alone. Fruit intake was lower in affected twins at baseline and higher at follow-up. The questionnaire recorded frequency, not quantity, and the switch to telephone assessment may have influenced the reported changes. Lifetime exposure to pollutants and solvents was more common in affected twins, but that finding did not survive correction for multiple comparisons and is vulnerable to recall bias.

Two identical pairs were no longer discordant by follow-up. In one, the originally affected twin had lived with Parkinson's for 15 years while the co-twin had only recently been diagnosed, a 14.5-year gap in onset. The other pair had a 12-year gap. The authors suggest the disease can appear at very different ages even in genetically identical people.

The authors caution that the small sample cannot establish equivalence between groups or rule out other influences on survival. Some secondary findings held up within individual categories, but none remained significant after correction across all 78 comparisons, so they need confirmation in larger studies. Work on the mechanisms linking disease progression to survival is still to come.