A family member with Parkinson’s disease confers the strongest risk for developing the disease, according to findings from the largest and most comprehensive systematic review and meta-analysis of Parkinson’s disease risk factors suitable for screening in primary care.

People with a first-degree relative with PD had a more than threefold higher odds for developing PD themselves, compared with those without an affected first-degree relative, based on a meta-analysis of data from 26 case-control studies, and people with any relative with PD had a 4.5-fold greater odds, according to data collected in 19 case-control studies, Dr. Alastair J. Noyce and his associates reported (Ann. Neurol. 2012 July 10 [doi: 10.1002/ana.23687]).

Dr. Noyce, a researcher in the Institute of Neurology, University College London, and his colleagues identified 202 English-language articles published during 1966-March 2011, of which 173 made it into the meta-analysis. Included studies involved several hundred thousand patients in cohort studies, and several tens of thousands in case-control studies. The new review and analysis used “an extensive search of observational studies to calculate effect sizes of multiple risk factors for PD,” the study authors wrote.

The meta-analysis found 19 risk factors that significantly linked with an altered risk – increased or decreased – for future development of PD, and assessed 11 additional factors that did not show a statistically significant link to PD. Following family history of PD, other strong associations identified in the meta-analysis included:

• Family history of tremor, which boosted the odds for development of PD 2.7-fold, based on results from 10 case-control studies.

• Constipation, considered an early symptom, which was associated with a 2.3-fold greater odds for PD, based on data from one case-control and one cohort study.

• Mood disorder, another early symptom, which was linked to an 86% higher odds of PD, based on data from 11 case-control and 2 cohort studies.

• Pesticide exposure, a risk factor that was linked to a 78% higher odds, according to data from 36 case-control and 2 cohort studies.

• Head injury, a risk factor associated with a 58% greater odds in 19 case-control studies.

Both constipation and mood disorders may correlate with brainstem involvement, an early effect of PD, the authors wrote.

The analysis identified four other risk factors that were linked to an increase in the odds of developing PD of less than 50% but still reached statistical significance: rural residence (43% greater), beta-blocker use (28%), farming or agricultural work (26%), and well water use (21%).

The remaining eight significant risk factors were all associated with reduced odds for PD. Leading this category was smoking. Current smokers had 56% lower odds, compared with never-smokers, based on data from 26 case-control studies and 7 cohort studies. People who had ever smoked had a 36% reduced odds compared with never smokers, and past smokers had a 22% reduced odds. Other protective factors were coffee drinking, linked to a 33% drop in odds; hypertension, linked to a 26% reduction in odds; use of nonsteroidal anti-inflammatory drugs, associated with 17% lower odds; and use of calcium channel blockers and alcohol, each of which was linked to 10% reduced odds.

The analyses failed to find significant links between development of PD and other proposed risk factors or protective agents, including oral contraceptives, surgical menopause, hormone-replacement therapy, aspirin, acetaminophen, statins, or a history of diabetes.

Dr. Noyce and his associates said that they had no disclosures.