Etiologies of Parkinsonism in a Century-Long Autopsy-Based Cohort (original) (raw)

Neuropathological correlates of parkinsonian disorders in a large Dutch autopsy series

Acta Neuropathologica Communications, 2020

The clinical diagnosis in patients with parkinsonian disorders can be challenging, and a definite diagnosis requires neuropathological confirmation. The aim of this study was to examine whether a clinical diagnosis of Parkinson’s disease (PD) and atypical parkinsonian disorders predict the presence of Lewy pathology (LP) and concomitant neuropathological lesions.We included 293 donors with a history of parkinsonism without dementia at disease onset, collected by the Netherlands Brain Bank (NBB) from 1989 to 2015. We retrospectively categorized donors according the International Parkinson and Movement Disorder Society clinical diagnostic criteria for PD (MDS-PD criteria) as ‘not PD’, ‘probable PD’ or ‘established PD’. We compared the final clinical diagnosis to presence of neuropathological lesions as defined by BrainNet Europe and National Institute on Aging – Alzheimer's Association guidelines.LP was present in 150 out of 176 donors (85%) with a clinical diagnosis of PD, in 8 out of 101 donors (8%) with atypical parkinsonian disorders and in 4 out of 16 donors (25%) without a definite clinical diagnosis. Independent from age at death, stages of amyloid-β, but not neurofibrillary tau or neuritic plaques, were higher in donors with LP compared to other types of pathology (p = 0.009). The MDS-PD criteria at a certainty level of ‘probable PD’ predicted presence of LP with a diagnostic accuracy of 89.3%. Among donors with LP, ‘established PD’ donors showed similar Braak α-synuclein stages and stages of amyloid-β, neurofibrillary tau and neuritic plaques compared to ‘not PD’ or ‘probable PD’ donors.In conclusion, both a clinical diagnosis of PD as well as MDS-PD criteria accurately predicted presence of LP in NBB donors. LP was associated with more widespread amyloid-β pathology, suggesting a link between amyloid-β accumulation and LP formation.

Parkinsons-Disease-in-the-Very-Old-Clinicopathological-Observations.pdf

Journal of Neuroscience and Neuropsychology, 2017

Background:The incidence of Parkinson syndrome (PS) increases dramatically after age 80 years. As the number of the very old (>80 years) is rising in the population, the number of PS cases would increase. In the general population the most common variant of PS is the Parkinson's disease (PD). PD is characterized by marked loss of substantia nigra neurons and Lewy Body (LB) inclusions. All the pathological variants of PS in the elderly however remain unknown. The objective of this study was to determine the frequency of different PS variants and their course in the elderly individuals. Results:We studied 30 PS cases that had onset age >80 years and came to autopsy between 1968 and 2015. Autopsy study was performed by certified neuropathologists. 21 of 30 cases had PD as the only movement disorder, two more patients had PD plus another movement disorder. Detailed analysis of 21 PD only cases revealed that mode of onset was the upper limb tremor, which is similar to the PD cases of all ages. They all improved on levodopa, as do most PD patients. Compared to younger onset PD cases, there was higher incidence of stroke and dementia in this age group. But stroke was not the cause of PD. The motor disability was more rapid than in the younger onset PD cases. We recommend that all elderly persons that have a clinical diagnosis of PS or PD should be treated with levodopa.

Fortnightly Review: Parkinsonism--recognition and differential diagnosis

BMJ, 1995

At first sight the diagnosis of Parkinson's disease might seem a fairly simple and straightforward affair, and indeed often it is. How many other medical conditions can sometimes be instantaneously recognised from a distance across a crowded street? The diagnosis of Parkinson's disease remains entirely clinical, made with eyes, ears, and hands without recourse to the laboratory. However, in two large recent studies from parkinsonian brain banks, one quarter of cases still carrying, at death, a diagnosis of idiopathic Lewy body Parkinson's disease made by a specialist did not have the disease.2 The rate of misdiagnosis at early stages by non-specialists is probably higher still. These findings at necropsy (that most ultimate of audits, and the quality control of our diagnostic skills) indicate a need for better diagnostic accuracy. In this article I shall consider the diagnostic process, possible pitfalls, and clinical clues (box 1) that may be useful in parkinsonism and Parkinson's disease. The list of conditions that can masquerade as Parkinson's disease is extensive, so I shall concentrate in the text on those that most frequently cause problems (box 2).

Clinical Study of Thirty Patients with Parkinson Disease and Associated Pathology

Journal of Medical Research and Surgery, 2021

We have clinically examined thirty patients with age ranging between 39 to 85 years old. We observed resting Tremor and Brakykinesia in 100% of patients examined and a family history of Parkinson Disease (PD) in 12%. We have found the following comorbidities: arterial hypertension 21%, diabetes 21%, language disorders 21%, neurobehavioral dysfunctions: 12%, neurosensory disorders, (hypoacusia) 12%, dizziness 8%, respiratory diseases 8%, constipation 8% and sleep disorders 8%. The following risks factors environmental conditions, stress, toxics, and previous cerebrovascular accident (1%) were observed. Parkinson disease motor and non-motor symptoms are discussed in details. PD can be associated with nneurobehavioral disorders (depression, anxiety), cognitive impairment (senile dementia), autonomic dysfunction, stress and aggressivity. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. A differential diagnosis of PD with atypical parkisonian syndromes, such as progressive supranuclear palsy, multiple system atrophy, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) is included.

Parkinson Disease Neuropathology

Archives of Neurology, 2002

To investigate the neuropathologic substrate for dementia occurring late in Parkinson disease (PD). Design: We identified 13 patients with a clinical diagnosis of PD who experienced dementia at least 4 years after parkinsonism onset (mean, 10.5 years) and subsequently underwent postmortem examination. Despite levodopa therapy, 9 patients later became severely impaired and nonambulatory, requiring total or near-total care; this included 4 patients treated with 1200 mg/d or more of levodopa (with carbidopa), which was consistent with loss of the levodopa response. These 13 patients were compared with 9 patients clinically diagnosed as having PD, but without dementia, who had undergone autopsies. Results: Twelve of 13 PD patients with dementia had findings of diffuse or transitional Lewy body disease as the primary pathologic substrate for dementia; 1 had progressive supranuclear palsy. This pathology also apparently accounted for the levodopa refractory state. Among the 12 PD patients with dementia, mean and median Lewy body counts were increased nearly 10-fold in neocortex

Parkinson's disease and parkinsonism in a longitudinal study: Two-fold higher incidence in men

Neurology, 2000

al. Stimulation of highaffinity adenosine A 2 receptors decreases the affinity of dopamine D 2 receptors in rat striatal membranes. Proc Natl Acad Sci USA 1991;88:7238 -7241. 37. Ledent C, Vaugeois J-M, Schiffmann SN, et al. Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A sub 2a receptor. Nature 1997;388:674 -678. 38. Hellenbrand W, Boeing H, Robra B-P, et al. Diet and Parkinson's disease II: a possible role for the past intake of specific nutrients: results from a self-administered food-frequency questionnaire in a case-control study. Neurology 1996;47:644 -650. 39. Sackett DL. Bias in analytic research. J Chronic Dis 1979;32: 51-63. 40. Morens DM, Grandinetti A, Davis JW, et al. Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease. Am J Epidemiol 1996;144:400 -404. 41. Ellenberg JH. Differential postmorbidity mortality in observational studies of risk factors for neurologic disorders.

Mortality in patients with Parkinson's disease

Acta Neurologica Scandinavica, 2009

After the introduction of L-dopa the mortality rate in Parkinson's disease (PD) patients has changed, but is still higher than in the background population. Mortality, age at death and cause of death in a group of PD patients compared with the background population were studied. The diagnosis on the death certificate were registered. The material consisted of 458 patients who in a period 1.4.1973-31.10.1991 were registered as having PD. Death in the period amounted to 253 patients. Median age of death was 77.29 years for men and 79.11 years for women. In the background population the median age at death was 80.69 years for men and 84.37 years for women. The SMR for men was 1.92 and for women 2.47. Infections, in particular lung infections, and heart diseases were the most common causes of death. Seventy percent of the death certificates had PD as a diagnosis. It is likely that several factors can influence the changed mortality of PD: more effective treatment, changing diagnostic practice, and inter-disease competition.

The progression of pathology in longitudinally followed patients with Parkinson’s disease

Acta Neuropathologica, 2008

The present study describes the pathological progression of longitudinally followed cases with levodopa-responsive Parkinson's disease who came to autopsy during the Sydney Multicenter Study of Parkinson's disease. Standardised clinical and neuropathological assessments over Wve epochs of time veriWed three diVerent clinicopathological groups. A group of younger onset patients with a typical long duration clinical course of Parkinson's disease. This group of cases had Lewy body distributions consistent with the Braak staging of disease. In this group, brainstem Lewy bodies dominate in those surviving to 5 years; by 13 years, 50% of cases have a limbic distribution of Lewy bodies; and by 18 years, all will have at least this pathological phenotype. Approximately 25% of cases had an early malignant, dementia-dominant syndrome and severe neocortical disease consistent with dementia with Lewy bodies. The last group had an older onset, shorter survival, and a more complex disease course with higher Lewy body loads and a higher proportion with additional neuropathologies. These cases with higher loads of Lewy bodies and shorter survivals suggest that widespread Lewy body pathology either occurs at the onset of clinical disease or rapidly inWltrates the brain. In these cases with shorter survivals, there was more plaque pathology, supporting a more aggressive and linked phenotype. Our data suggest that the selection of similar study cohorts by pathology alone would not be able to diVerentiate the three diVerent phenotypes identiWed. The data are also not consistent with a unitary concept of the pathogenesis of Lewy body disease.

Early predictors of mortality in parkinsonism and Parkinson disease

Neurology

ObjectiveTo examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease.MethodsOne hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality.ResultsThe standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50–2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive su...