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Lewy pathology occurs in 8-17% of neurologically normal people age >60, termed incidental Lewy body disease (iLBD). It is often assumed to represent preclinical Parkinson disease (PD). However, some iLBD cases have diffuse pathology inconsistent with preclinical PD. We analyzed iLBD cases (α-synuclein immunohistochemistry) using the Braak PD staging scheme and determined if some had a neuropathological pattern suggestive of preclinical dementia with Lewy bodies (DLB). Of the 235 brains examined, 34 had iLBD (14.5%) and all but one could be assigned a Braak PD stage. The distribution of α-synuclein pathology in the 33 cases fell into three patterns: (1) diffuse cortical and subcortical α-synuclein pathology; (2) no cortical α-synuclein pathology, but a caudal-to-rostral ascending pattern, primarily involving brainstem; and (3) intermediate between these two categories. Also, 6/33 cases failed to follow the pattern of contiguous spread proposed by Braak. These findings suggest dichotomy in the distribution of iLBD: some cases fit the Braak ascending scheme, conceptually consistent with preclinical PD, whereas others displayed prominent cortical involvement that might represent preclinical DLB., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Background: The evidence for increased risk of dementia in relatives of patients with Parkinson disease (PD) remains conflicting., Objective: To study the risk of cognitive impairment or dementia in first-degree relatives of patients with PD., Design, Setting, and Participants: We conducted a historical cohort study of 1019 first-degree relatives of 162 patients with PD and of 858 relatives of 147 matched controls representative of the population of Olmsted County, Minnesota. In addition, we studied 2716 first-degree relatives of 411 patients with PD referred to Mayo Clinic., Main Outcome Measures: We administered via telephone a cognitive test directly to relatives or a dementia questionnaire to proxies. For relatives reported by proxies to have dementia, we obtained copies of their medical records to confirm the diagnosis. We also obtained dementia information from a medical records-linkage system., Results: In the overall population-based sample, the risk of cognitive impairment or dementia was increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.37; 95% confidence interval, 1.03-1.81; P = .03) and was particularly increased in relatives of patients with onset of PD at age 66 years or younger (youngest tertile; hazard ratio, 1.73; 95% confidence interval, 1.21-2.46; P = .003). The findings were consistent in several sensitivity analyses. In the referral-based sample, the risk of cognitive impairment or dementia in relatives increased with younger age at onset of PD but did not vary by other clinical characteristics., Conclusion: Cognitive impairment or dementia may share familial susceptibility factors with PD (genetic or nongenetic).

Objective: There is increasing laboratory evidence for a neuroprotective effect of estrogen; however, the clinical and epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent cognitive impairment or dementia., Methods: We included all women who underwent unilateral or bilateral oophorectomy before the onset of menopause for a non-cancer indication while residing in Olmsted County, MN, from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 813 women with unilateral oophorectomy, 676 women with bilateral oophorectomy, and 1,472 referent women. Women were followed through death or end of study using either direct or proxy interviews., Results: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of cognitive impairment or dementia compared to referent women (hazard ratio [HR] = 1.46; 95% CI 1.13 to 1.90; adjusted for education, type of interview, and history of depression). The risk increased with younger age at oophorectomy (test for linear trend; adjusted p < 0.0001). These associations were similar regardless of the indication for the oophorectomy, and for women who underwent unilateral or bilateral oophorectomy considered separately., Conclusions: Both unilateral and bilateral oophorectomy preceding the onset of menopause are associated with an increased risk of cognitive impairment or dementia. The effect is age-dependent and suggests a critical age window for neuroprotection.

In an inception cohort of 196 Olmsted County, Minnesota, residents with Parkinson's disease (PD) first recognized in 1976 to 1995, we tested whether the increased risk of bone fractures is associated with concomitant dementia. Using the data resources of the Rochester Epidemiology Project, information about PD, dementia, other clinical risk factors for fracture and fracture events was obtained from review of complete inpatient and outpatient medical records spanning each subject's residence in the community. Compared to an equal number of age- and sex-matched non-PD referent subjects from the community, PD patients were at a 2.2-fold increased risk of fractures generally and a 3.2-fold greater risk of hip fractures specifically. Adjusting for age, the independent predictors of overall fracture risk in the PD subjects included female sex (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.1-2.3), dementia (HR, 1.6; 95% CI, 1.1-2.4) and chronic depression, which was associated with a reduced risk (HR, 0.4; 95% CI, 0.2-0.8). Hip fractures were predicted by dementia (HR, 2.2; 95% CI, 1.2-4.1). The increased fracture risk in patients with PD is not entirely explained by concomitant dementia, and additional study is needed to determine the relative contributions to fracture risk of falls versus bone loss in these patients., ((c) 2006 Movement Disorder Society.)

We report the clinical, neuropsychological, electroencephalographic and radiologic findings in a kindred with varying clinical presentations of a neurodegenerative disorder. Postmortem examination of one member with clinically suspected corticobasal degeneration (CBD) revealed nonspecific histopathology maximally involving the frontoparietal cortex with negligible degenerative changes in the basal ganglia and substantia nigra. The findings in this and other kindreds demonstrate that (1) similar findings on ancillary testing can occur in relatives presumably suffering from the same pathophysiologic process despite dissimilar clinical presentations, (2) the 'CBD syndrome' is not specific for CBD, (3) extrapyramidal dysfunction can exist in the absence of appreciable basal ganglia and nigral degeneration, (4) nonspecific histopathology can underlie familial focal/asymmetric cortical degeneration syndromes and (5) many of the findings in CBD are comparable to those reported in frontotemporal dementia., (Copyright 2002 S. Karger AG, Basel)

We studied the influence of three sets of diagnostic criteria on the age- and sex-specific incidence of Parkinson's disease (PD) among residents of Olmsted County, Minnesota, for the period 1976 to 1990. Incidence cases of parkinsonism were detected using the medical records-linkage system of the Rochester Epidemiology Project. PD was separated from other types of parkinsonism using strict, intermediate, and broad criteria. We found 154 incident cases of PD using the strict criteria, 215 using the intermediate criteria, and 266 using the broad criteria. The incidence rate was consistently higher for men across all ages with all three sets of criteria; however, sex differences were more striking at older ages when using the broad criteria. In men above age 79 years, the incidence rate of PD declined with strict criteria, remained stable with intermediate criteria, and increased with broad criteria. The impact of diagnostic criteria on the age-specific incidence curve was less striking for women. When using the broad criteria, the risk of PD increased constantly with age in both sexes, suggesting that PD is an aging-related disease. Our findings suggest that the diagnostic criteria used to separate PD from other types of parkinsonism influence the magnitude of PD incidence and its distribution by age and sex.

In four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa-responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.