Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease

Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men.     

Meta‐analysis of early nonmotor features and risk factors for Parkinson disease

Objective:

To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population‐based screening.

Methods:

A systematic review and meta‐analysis of risk factors for PD.

Results:

The strongest associations with later diagnosis of PD were found for having a first‐degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10–3.57), constipation (relative risk [RR], 2.34; 95% CI, 1.55–3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39–0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta‐blockers, farming occupation, and well‐water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti‐inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results.

Interpretation:

The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them. ANN NEUROL 2012     

Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease.

Inflammation and oxidative stress have been implicated as pathogenic mechanisms in Parkinson's disease (PD). Evidence from in vitro and animal studies suggests a possible protective role of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. We investigated the risk of PD associated with use of aspirin and nonaspirin NSAIDs in a population-based case-control study among enrollees of Group Health Cooperative, a health maintenance organization in the Seattle area. Subjects included 206 cases between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 randomly selected controls frequency-matched by age, sex, duration of enrollment, and clinic. We obtained information on participants' age, smoking, and medical history from interview. Exposure to NSAIDs was ascertained from an automated pharmacy database. Medications filled within 5 years of the interview were excluded. After adjusting for age, sex, smoking, duration of enrollment, and clinic, the risk of PD among individuals who received nonaspirin NSAIDs between 1977 and 1992 was 0.90 (95% CI: 0.59-1.35) and 1.67 (95% CI: 0.60-4.60) between 1993 and 2002. Use of ibuprofen was not associated with PD (OR: 0.89; 95% CI: 0.60-1.32). The risk of PD associated with aspirin or aspirin-containing medications was 0.74 (95% CI: 0.49-1.12). We observed no trend in risk according to number of fills for these drugs. Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs.     

Comorbid cancer in Parkinson's disease

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age‐ and sex‐matched control subjects identified during two periods (1994–1995 and 2000–2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD–cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD–cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non‐PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54–1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70–1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40–5.2; after PD, RR = 1.6; 95% CI 0.71–3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking. © 2010 Movement Disorder Society.     

Metabolic markers or conditions preceding Parkinson's disease: A case‐control study

Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson's disease (PD); however, results remain conflicting. We further investigated these associations using a case–control study design. We used the medical records–linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records–linkage system to abstract information about body mass index (BMI), cholesterol level, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cutoffs for BMI level (BMI ≥ 25 or BMI ≥ 30 kg/m²) and 3 cutoffs for cholesterol levels (>200, >250, or >300 mg/dL). Neither a diagnosis of hypertension or the documented use of antihypertensive medications was significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65–1.54; P = .99) nor was a diagnosis of diabetes mellitus or the use of glucose‐lowering medications (OR, 0.77; 95% CI, 0.37–1.57; P = .47). Our study, based on historical information from a records‐linkage system, does not support an association between BMI, cholesterol level, hypertension, or diabetes mellitus with later development of PD. © 2012 Movement Disorder Society     

Familial aggregation of Parkinson's disease in a multiethnic community‐based case‐control study

To assess the familial aggregation of Parkinson's disease (PD), we compared the cumulative incidence of PD among first‐degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n = 573) during 1994 to 1995 within Kaiser Permanente Medical Care Program of Northern California and recruited 496 cases (87%) for the case‐control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in‐person structured interview. We used the reconstructed cohort approach that provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared with relatives of controls (2.0 vs. 0.7%; relative risk (RR) = 3.4, 95% confidence interval (CI) 1.9–5.9; P = 0.0001). The degree of familial aggregation was higher among first‐degree relatives of Hispanic PD cases compared with Hispanic controls (3.7% vs. 0.4%; RR = 8.5, 95% CI 1.0–68.9) than it was among non‐Hispanic Caucasian cases and controls (2.0% vs. 0.8%; RR = 2.7, 95% CI 1.5–5.1; P = 0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR = 5.4, 95% CI 1.8–16.0) than among parents (RR = 2.7, 95% CI 1.3–5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population. © 2010 Movement Disorder Society     

Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study

Purpose: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture. Methods: We performed a case‐control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals with a hip fracture during the period 1996–2004. Controls (n = 27,575) were frequency matched by age and gender. Information on use of AEDs, other drugs, and hospital contacts was available from local registers. Odds ratios (ORs) with 95% confidence intervals (CI) for hip fracture were estimated by unconditional logistic regression. Results: Fracture risk was increased with ever use of any AED (OR: 1.31; 95% CI: 1.16–1.48). The risk was also increased with use of only enzyme inducing (OR: 1.31; 95% CI: 1.14–1.51), but not with use of only noninducing AEDs (OR: 1.03; 95% CI: 0.77–1.37). Current (OR: 1.92; 95% CI: 1.58–2.33) and recent use, as well as high daily (OR: 1.50; 95% CI: 1.24–1.82) and cumulative dose increased fracture risk, but long treatment duration or previous use did not. The risk was modified by the presence of an epilepsy diagnosis. Conclusion: Use of AEDs modestly increases the risk of hip fracture. The risk increase is probably associated to a higher degree with a dose dependent effect on CNS with current and recent use, than with an effect on bone tissue.     

A case–control study of multiple system atrophy in Korean patients

A few case–control studies of multiple system atrophy (MSA) have been reported in Western populations. In this study, we included various epidemiological factors to evaluate whether the risk factors for MSA differed in Korean and Western populations. A total of 100 consecutive MSA patients and 104 controls at two referral hospitals participated. Information was obtained through face‐to‐face interviews using a structured questionnaire: history of living area, occupational history, food habits, alcohol and tobacco consumption, and use of drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using logistic regression. The multivariate logistic regression analysis revealed that use of antihypertensive medication (OR = 0.30 [0.12–0.78]) and vitamins (OR = 0.30 [0.14–0.64]) and consumption of meat and poultry (OR = 0.27 [0.13–0.56]) were associated with decreasing risk for MSA, whereas use of herbal medications (OR = 3.17 [1.28–7.84]) was associated with increasing risk for MSA. In univariate analysis adjusted for age, sex, education level, and recruitment center, use of aspirin (OR = 0.21 [0.07–0.61]) and coffee consumption (OR = 0.44 [0.23–0.84]) were significantly less frequent in MSA patients than in controls, whereas heavy smoking (≥40 pack‐years) was significantly more prevalent in MSA patients than in controls (OR = 3.44 [1.05–11.23]). There was no difference in living area, participation in farming, or exposure to agrichemicals and solvents between groups. This study showed that MSA in Korea is characterized by risk factors that are both similar to and different from those affecting Western populations and that herbal medicines constitute a new MSA risk factor for the Korean population. © 2010 Movement Disorders Society     

Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested,matched case‐control study

Gau C‐S, Chang C‐J, Tsai F‐J, Chao P‐F, Gau SS‐F. Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case‐control study.
Bipolar Disord 2010: 12: 253–263. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwan’s National Health Insurance Dataset. Methods: The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex‐, age‐, and index date‐matched bipolar disorder patients without hypothyroidism from 1996–2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model. Results: Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07–2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70–3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10–2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68–3.25). There was a dose‐response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21–1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020). Conclusions: Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.     

Major life events and risk of Parkinson's disease

Major life events such as divorce, death of a spouse or a child, or long‐term unemployment are stressful to most people and animal models have suggested a link between stress and onset of parkinsonian symptoms. In a large case‐control study based on nationwide registries, we aim to address whether major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose‐response manner (P < 0.0001). Compared to no events, three or more events were associated with a 42% lower risk of PD (OR = 0.58; 95 % CI: 0.34–0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04–1.29) and among men (1.47; 1.18–1.82) and women (1.30; 1.05–1.61) who have never been employees. The lower risk of Parkinson's disease among men who had experienced life events was unexpected but might suggest a general “risk avoidance behavior” in Parkinson's patients. © 2010 Movement Disorder Society     

Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study

Matinolli M, Korpelainen JT, Sotaniemi KA, Myllylä VV, Korpelainen R. Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study.
Acta Neurol Scand: 2011: 123: 193–200.
© 2010 John Wiley & Sons A/S. Objectives – To evaluate the risk factors for recurrent falling and mortality in Parkinson’s disease (PD) in a prospective study design. Materials and methods – One hundred and twenty‐five PD patients were included in the study. Baseline medical data were collected, and patients were clinically tested for mobility and balance. Falls were prospectively recorded for 2 years. Mortality was documented 4 years after the baseline. Results – Seventy‐nine patients reported altogether 3125 falls during the follow‐up, and 59 patients were classified as recurrent fallers. Altogether 126 fall injuries including six fractures were reported. Eighteen patients had died by the time of the hospital chart review. History of falling (OR 3.02, 95% CI 1.23–7.44) and the Unified Parkinson’s Disease Rating Scale activities of daily living score (OR 1.13, 95% CI 1.04–1.22) were independent risk factors for recurrent falling in PD, whereas slow walking speed (OR 16.28, 95% CI 1.85–142.97) was an independent risk factor for mortality in PD. Conclusions – History of falling and disease severity indicate increased risk of recurrent falls in PD, while patients with slow walking speed may have an increased risk of mortality. Recurrent falling was not associated with increased risk of mortality in PD in this study.     

Depression and the subsequent risk of Parkinson's disease in the NIH‐AARP Diet and Health Study

We conducted a case‐control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH‐AARP Diet and Health Study follow‐up survey. Physician‐diagnosed depression and PD were self‐reported with information on the year of diagnosis in the following categories: before 1985, 1985–1994, 1995–1999, and 2000–present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995–1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985–1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% CI = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD. © 2010 Movement Disorder Society     

Risk of incident depression in patients with Parkinson disease in the UK

Background: Non‐motor symptoms are not widely recognized in patients with Parkinson disease (PD). We sought to assess the incidence rate as well as the risk of depression in newly diagnosed patients with PD and to compare it to PD‐free controls. Methods: We conducted a population‐based follow‐up study with a nested case–control analysis based on data from the UK‐based General Practice Research Database (GPRD). We included PD patients ≥ aged 40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed incidence rates (IRs) and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]). Results: The IR of depression in newly diagnosed PD in the UK community was 26.0 (95% CI 22.9–29.5) per 1000 person‐years. The risk of developing depression was increased almost twofold in patients with PD when compared to patients without PD (adj. OR 1.89; 95% CI 1.49–2.40). The increased relative risk was most pronounced in women and in individuals 40–69 years of age. Long‐term users of levodopa had an increased depression risk when compared to short‐term users. Conclusions: Patients with PD are at an approximately twofold increased risk of being diagnosed with depression compared to the PD‐free population.     

Confirmation of LRRK2 S1647T variant as a risk factor for Parkinson’s disease in Southern China

Background: Leucine‐rich repeat kinase 2 (LRRK2) S1647T has been identified as a risk variant for Parkinson’s disease (PD) in Han Chinese. Methods: To replicate the association of LRRK2 S1647T with risk of PD, we conducted a case–control study of this variant involving 406 PD subjects and 412 controls from southern mainland China. Results: The results showed that the frequency of A allele was higher in patients with PD (OR = 1.238, 95% CI: 1.015–1.510, P = 0.035) compared to controls. In a multivariate logistic regression analysis with the disease group (patients with PD vs. controls) as the dependent variable and genotype as an independent factor adjusting for the effect of age and gender, the homozygous S1647T genotype (AA) was associated with an increased risk of PD (OR = 1.815, 95% CI:1.270–2.594, P = 0.001). The pooled analysis of present data and the data from the previous work demonstrated that the frequency of A allele was higher in patients with PD (OR = 1.2, 95% CI: 1.09–1.32, P < 0.0001). Conclusions: LRRK2 S1647T increases the risk of Parkinson’s disease in southern China.     

Combined effects of smoking,coffee, and NSAIDs on Parkinson's disease risk

Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti‐inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two‐way and three‐way combinations of these factors, a case–control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking, coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two‐way and three‐way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose–response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06–0.29). Whether this finding reflects true biologic protection needs to be investigated. © 2007 Movement Disorder Society     

Association of Parkinson's disease with infections and occupational exposure to possible vectors

The ultimate causes of idiopathic Parkinson's disease (PD) are not fully known, but environmental and occupational causes are suspected. Postencephalitic parkinsonism has been linked to influenza, and other viral infections have also been suspected to relate to PD. We estimated the relationship between PD and both infections and possible vectors of infection (i.e., animal and human) in a population-based, case-control study in British Columbia, Canada. We recruited 403 cases detected by their use of antiparkinsonian medications and 405 controls from the registrants of the provincial universal health insurance plan. Severe influenza was associated with PD (odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.16-3.48), although this effect was attenuated when reports were restricted to those occurring 10 or more years before diagnosis. Childhood illnesses were inversely associated with PD, particularly red measles (OR: 0.65; 95% CI: 0.48-0.90). Several animal exposures were associated with PD, with statistically significant effects for cats (OR: 2.06; 95% CI: 1.09-3.92) and cattle (OR: 2.23; 95% CI: 1.22-4.09). Influenza infection may be associated with PD. The inverse relationships with childhood infections may suggest an increased risk with subclinical or asymptomatic childhood infections. Occupational exposure to animals may increase risk through transmission of infections or may indicate exposure to another agent of interest (e.g., bacterial endotoxin). ? 2012 Movement Disorder Society.     

Synergistic effect of two oxidative stress‐related genes (heme oxygenase‐1 and GSK3β) on the risk of Parkinson’s disease

Background: Oxidative stress is a central factor in the pathogenesis of Parkinson’s disease (PD). Heme oxygenase‐1 (HO‐1) is an antioxidant protein expressed in response to oxidative challenge, and its expression levels are inversely correlated with glycogen synthase kinase‐3β (GSK3β) activity. Underexpression of HO‐1 in concert with an upregulation of GSK3β would result in a less effective antioxidant response and might increase the risk of PD. Methods: We examined two functional polymorphism in the promoter regions of HO‐1 (?413, rs2071746) and GSK3β (?157, rs6438552) in a group of 251 Spanish patients with PD and 234 controls. Results: Subjects carrying both the HO‐1 (?413, rs2071746) TT genotype and the GSK3β (?157, rs6438552) TT genotype had a four times higher risk of developing PD than subjects without these genotypes (adjusted by age and sex OR = 4.12; 95% CI = 1.45–11.71; Bonferroni corrected P = 0.024). Conclusions: Considering synergistic effects between polymorphisms in oxidative stress‐related genes may help in determining the risk profile for PD.     

Parkinson's disease and risk of mortality: meta‐analysis and systematic review

To evaluate the existing prospective observational studies on the morality risk among Parkinson's disease (PD) patients and determine the overall risk ratio (RR) of mortality by conducting a meta‐analysis and systematic review. Original articles published in English were searched in PubMed and Embase databases prior to March 2013. Only prospective observational studies providing adjusted risk estimates related to PD and future mortality were considered eligible. Pooled adjusted RR and 95% confidence interval (CI) were computed either by fixed‐effects models or by random‐effects models. Eight studies with 72,833 participants were identified and analysed. In the pooled analyses, patients with PD had a greater risk of all‐cause mortality (RR = 2.22; 95% CI: 1.78–2.77). Subgroup analyses based on the design, gender, follow‐up duration and sample size showed that a consistent positive association between PD and the mortality risk in each subgroup. However, no statistical significance was found for the baseline age <65 years (RR = 1.42; 95% CI: 0.72–2.77). PD patients with dementia had particularly high mortality risks (RR = 3.78; 95% CI: 2.06–6.92). This meta‐analysis indicated that among patients with PD, the all‐cause mortality increased by 2.22‐fold compared with the general population. PD patients with dementia particularly had higher risks of mortality.     

Long‐term employment of adults with childhood‐onset epilepsy: A prospective population‐based study

Purpose: Our aim was to determine the long‐term employment and predictive factors in adults with childhood‐onset epilepsy living in the community. Methods: A population‐based incidence cohort of 144 children prospectively followed since their first unprovoked seizure before the age of 16 years up to a mean age of 48. Results: At a mean age of 23 years (range 18–35 years) 85 (71%) of 119 patients living in the community were employed. Predictive of employment at a mean age of 23 were normal intelligence [odds ratio (OR) 14.5, 95% confidence interval (CI) 4.5–46.8, p < 0.01], vocational education (OR 15.2, 95% CI 2.9–79.9, p < 0.01), and age at onset of epilepsy older than 6 years (OR 4.9, 95% CI 1.3–19.2, p = 0.02). At the mean age of 48 years (range 43–59 years), 45 (59%) of 76 patients living in the community were employed, as were 63 (78%) of 81 controls (patients vs. controls, p = 0.01). In 40 (53%) of 76 surviving patients employed between age 23 and 48, four factors were found to predict employment: normal intelligence (OR 15.8; 95% CI 2.4–102.4, p < 0.01), having offspring (OR 6.1; 1.5–25.0, p = 0.01), uninterrupted 5‐year terminal remission (5YTR) from age 23 to age 48 (OR 4.8; 1.1–19.9, p = 0.03), and no history of status epilepticus (OR 12.8; 1.8–90.9, p = 0.01). Conclusions: Normal intelligence, onset of epilepsy at age older than 6, and good vocational education appear to predict employment in early adulthood. Normal intelligence, having offspring, uninterrupted remission, and no history of status epilepticus appear to predict lasting employment into middle age.