James H. Bower

Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990.

Objective: Limited information is available on the frequency and distribution of parkinsonism as a syndrome. We studied the incidence of parkinsonism and its specific types among residents of Olmsted County, MN, for the period from 1976 through 1990. Methods: We used the medical records linkage-system of the Rochester Epidemiology Project to identify all individuals whose records contained documentation of any form of parkinsonism, related neurodegenerative diseases, or tremor of any type. A nurse abstractor screened the records, and, when applicable, a neurologist reviewed them to determine the presence of parkinsonism using specified diagnostic criteria and to define the year of onset. Results: We found 364 incident cases of parkinsonism: 154 with PD (42%), 72 with drug-induced parkinsonism (20%), 61 unspecified (17%), 51 with parkinsonism in dementia (14%), and 26 with other causes (7%). The average annual incidence rate of parkinsonism (per 100,000 person-years) in the age group 50 to 99 years was 114.7; incidence increased steeply with age from 0.8 in the age group 0 to 29 years to 304.8 in the age group 80 to 99 years. The cumulative incidence of parkinsonism assuming no competing causes of death was 7.5% to age 90 years. PD was the most common type of parkinsonism, followed by parkinsonism in dementia in men and drug-induced parkinsonism in women. Men had higher incidence than women at all ages for all types of parkinsonism except drug-induced. Conclusions: Parkinsonism is a common disease among the elderly; its incidence increases steeply with advancing age and is consistently higher in men. The distribution by type changes with age and gender.

Anxiety disorders and depressive disorders preceding Parkinson's disease: a case-control study.

We studied the association between preceding psychiatric disorders and Parkinsons disease (PD) using a case‐control design. We used the medical records‐linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, during the years 1976–1995. Each case was matched by age (±1 yr) and sex to a general population control. We reviewed the complete medical records of cases and control subjects to detect preceding psychiatric disorders. The frequency of psychiatric disorders was higher in cases than in control subjects; the odds ratio was 2.2 for anxiety disorders (95% confidence interval [95% CI] = 1.4–3.4; p = 0.0003), 1.9 for depressive disorders (95% CI = 1.1–3.2; p = 0.02), and 2.4 for both anxiety disorders and depressive disorders occurring in the same individual (95% CI = 1.2–4.8; p = 0.02). When we restricted analyses to disorders present 5 years or more before the onset of motor symptoms of PD, the association with depressive disorders lost statistical significance. However, the association with anxiety disorders remained significant for disorders present 5, 10, or 20 years before onset of motor symptoms. Our results suggest that anxiety disorders and depressive disorders are associated with PD and that the causative process or the risk factors underlying PD are present many years before the appearance of motor symptoms.

Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990

Information on the incidence of progressive supranuclear palsy (PSP) is limited; incidence rates for multiple system atrophy (MSA) are not available. We studied the incidence of PSP and MSA in Olmsted County, Minnesota, for the years 1976 to 1990. This study was part of a larger investigation of all forms of parkinsonism. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects whose records contained documentation of any form of parkinsonism, related neurodegenerative diseases, or tremor of any type. A nurse abstractor screened the records and, when applicable, a neurologist reviewed them to determine the presence or absence of parkinsonism. Cases of parkinsonism were classified using specified diagnostic criteria. Population denominators were derived from census data and were corrected by removing prevalent cases of parkinsonism. Over the 15 years of the study, we found 16 incident cases of PSP and nine incident cases of MSA. No cases of PSP or MSA had onset before age 50 years. The average annual incidence rate (new cases per 100,000 person-years) for ages 50 to 99 years was 5.3 for PSP and 3.0 for MSA. The incidence of PSP increased steeply with age from 1.7 at 50 to 59 years to 14.7 at 80 to 99 years, and was consistently higher in men. Median survival time from symptom onset was 5.3 years for PSP and 8.5 years for MSA. The incidence of PSP increases with age and is consistently higher in men at all ages. PSP and MSA are more common than previously recognized.

Risk tables for parkinsonism and Parkinson's disease

We applied the incidence rates of parkinsonism and Parkinsons disease (PD) from Olmsted County, MN (1976-1990) to a hypothetical cohort undergoing the mortality rates observed in Minnesota, and computed the lifetime risk and the remaining lifetime risk of developing parkinsonism and PD. These risks were compared to cumulative incidences that do not take competing risks of death into account. The lifetime risk of developing parkinsonism from birth was 4.4% for men and 3.7% for women (ratio = 1.2). The corresponding risk of developing PD was 2.0% for men and 1.3% for women (ratio = 1.5). Because of the opposite effect of higher incidence and higher mortality rates in men, the lifetime risks were only slightly higher in men than in women. Lifetime cumulative incidences were consistently higher than lifetime risks; this difference was more pronounced in men and in older subjects. Lifetime risk estimates are useful in clinical practice, epidemiologic research, and public health.

Human Brain Derived Neurotrophic Factor (BDNF) Genes, Splicing Patterns, and Assessments of Associations with Substance Abuse and Parkinson's Disease

Potential roles for variants in the human BDNF gene in human brain disorders are supported by findings that include: (a) influences that this trophic factor can exert on important neurons, brain regions, and neurotransmitter systems, (b) changes in BDNF expression that follow altered neuronal activity and drug treatments, and (c) linkages or associations between genetic markers in or near BDNF and human traits and disorders that include depression, schizophrenia, addictions, and Parkinsons disease. We now report assembly of more than 70 kb of BDNF genomic sequence, delineation of 7 noncoding and 1 coding human BDNF exons, elucidation of BDNF transcripts that are initiated at several alternative promoters, identification of BDNF mRNA splicing patterns, elucidation of novel sequences that could contribute to activity‐dependent BDNF mRNA transcription, targeting and/or translation, elucidation of tissue‐specific and brain‐region‐specific use of the alternative human BDNF promoters and splicing patterns, identification of single nucleotide polymorphism (SNP), and simple sequence length polymorphism (SSLP) BDNF genomic variants and identification of patterns of restricted haplotype diversity at the BDNF locus. We also identified type 2 BDNF‐locus transcripts that are coded by a novel gene that is overlapped with type 1 BDNF gene and transcribed in reverse orientation with several alternative splicing isoforms. Association studies of BDNF variants reveal no associations with Parkinsons disease. Comparisons between substance abusers and controls reveal modest associations. These findings increase interest in this diverse human gene. Published 2005 Wiley‐Liss, Inc.

Smoking, alcohol, and coffee consumption preceding Parkinson’s disease A case-control study

Objective: To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. Methods: The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (±1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. Results: For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose–effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age <72 years and to men. The OR for cigarette smoking was 0.69 (95% CI = 0.45 to 1.08, p = 0.1). The authors found no association between PD and alcohol consumption. Extreme or unusual behaviors such as tobacco chewing or snuff use and a diagnosis of alcoholism were significantly more common in control subjects than cases. Conclusions: These findings suggest an inverse association between coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

Increased risk of parkinsonism in women who underwent oophorectomy before menopause

Objective: There is increasing laboratory evidence for a neuroprotective effect of estrogen on the nigrostriatal pathway; however, the epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent parkinsonism. Methods: We included all women who underwent either unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987 while residing in Olmsted County, MN. Each member of the oophorectomy cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed through death or end of study using a combination of direct or proxy interviews, neurologic examinations, medical records in a records-linkage system, and death certificates. Results: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with referent women (HR 1.68; 95% CI 1.06 to 2.67; p = 0.03), and the risk increased with younger age at oophorectomy (test for linear trend; p = 0.01). The findings were similar regardless of the indication for the oophorectomy, and for unilateral or bilateral oophorectomy considered separately. The findings were also consistent for Parkinson disease alone, but did not reach significance. Conclusions: Both unilateral and bilateral oophorectomy performed prior to menopause may be associated with an increased risk of parkinsonism and the effect may be age-dependent. However, our findings await independent replication.

Hysterectomy, menopause, and estrogen use preceding Parkinson's disease: An exploratory case‐control study

We studied the association of Parkinsons disease (PD) with type of menopause (natural or surgical), age at menopause, and postmenopausal estrogen replacement therapy using a case‐control design. We used the medical records‐linkage system of the Rochester Epidemiology Project to identify 72 women who developed PD in Olmsted County, MN, during the twenty years 1976–1995. Each incident case was matched by age (± 1 year) to a general population control subject. We collected exposure data through review of the complete medical records of cases and control subjects in the system. PD cases had undergone hysterectomy (with or without unilateral oophorectomy) significantly more often than control subjects (odds ratio [OR] = 3.36; 95% confidence interval [CI] = 1.05–10.77). In addition, PD cases had experienced early menopause (≤ 46 years) more commonly than control subjects (OR = 2.18; 95% CI = 0.88–5.39). Finally, PD cases had used estrogens orally or parenterally for at least 6 months after menopause less frequently (8%) than control subjects (14%; OR = 0.47; 95% CI = 0.12–1.85). However, the findings for early menopause and estrogen replacement therapy were not statistically significant. Despite the limited sample size of this exploratory study, we hypothesize that there is an increased risk of PD in conditions causing an early reduction in endogenous estrogen. This hypothesis needs to be confirmed in a larger study.

Head trauma preceding PD: A case-control study

Objective: To investigate the association of PD with preceding head trauma using a case-control study design. Methods: The medical records-linkage system of the Rochester Epidemiology Project was used to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. The complete medical records of cases and controls in the system were reviewed to detect preceding episodes of head trauma. Results: The frequency of head trauma overall was significantly higher in cases than in controls (odds ratio [OR] = 4.3; 95% CI = 1.2 to 15.2). Compared with subjects who never experienced a trauma, subjects who experienced a mild head trauma with only amnesia had no increased risk; however, subjects who experienced a mild head trauma with loss of consciousness or a more severe trauma had an OR of 11.0 (95% CI = 1.4 to 85.2). Although not significant, head trauma resulting in hospitalization was more frequent in cases than in control subjects (OR = 8.0; 95% CI = 1.0 to 64.0). Whereas the OR was higher for men than women and for patients with later onset of PD than for patients with earlier onset, these differences were not significant. Conclusions: These results suggest an association between head trauma and the later development of PD that varies with severity. Although the OR is high (4.3), the population attributable risk is only 5% because head trauma is a relatively rare event.

Medical records documentation of constipation preceding Parkinson disease: A case-control study

Objective: Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Methods: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, 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 ascertain the occurrence of constipation preceding the onset of PD (or index year). Results: Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Conclusions: Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.