Parkinson disease, dementia, and alzheimer disease: Clinicopathological correlations

Boller, Fraņois; Mizutani, Tetsuya; Roessmann, Uros; Gambetti, Pierluigi

doi:10.1002/ana.410070408

Cited by 455 publications

(133 citation statements)

References 37 publications

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“…679 AD pathology is also encountered in patients with PD, who have six times the expected prevalence compared with an agedmatched control population. 680,681 Along these lines, patients diagnosed with AD are more likely than controls to develop parkinsonian motor features during life and to have PD pathology at postmortem. 682,683 Neuroimaging and autopsy studies demonstrate that there are also cholinergic deficits in patients with PD-D, and that these are more profound and occur at an earlier stage of the disease than found in patients with AD.…”

Section: 668mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

771

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Section: 668mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

771

658

View full text Add to dashboard Cite

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“…Neuropathological basis of dementia in the idiopathic PD remains controversial. Many PD patients have substantial load of Alzheimer's histopathological features [15,17,48,49]. There is evidence that dementia in PD is associated more closely with cortical deposition of the hallmark component of Lewy bodies, α-synuclein, than with Alzheimer's pathology [2,43,68], although this conclusion is disputed by some authors [82].…”

Section: Introductionmentioning

confidence: 99%

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

Bychkov

Joyce

et al. 2008

Neurobiology of Aging

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Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors. We investigated changes in the expression of arrestins and GRKs in the striatum of patients with Parkinson's disease without (PD) or with dementia (PDD) at post mortem using Western blotting and ribonuclease protection assay. Both PD and PDD groups had similar degree of dopamine depletion in all striatal regions. Arrestin proteins and mRNAs were increased in the PDD group throughout striatum. Protein and mRNA of GRK5, the major subtype in the human striatum, and GRK3 were also upregulated, whereas GRK2 and 6 were mostly unchanged. The PD group had lower concentration of arrestins and GRKs than the PDD group. There was no statistical link between the load of Alzheimer's pathology and the expression of these signaling proteins. Upregulation of arrestins and GRK in PDD may confer resistance to the therapeutic effects of levodopa often observed in these patients. In addition, increased arrestin and GRK concentrations may lead to dementia via perturbation of multiple signaling mechanisms.

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“…For example, Tau immunoreactive pathology is detected in each of the ␣-synucleinopathies. The incidence of NFTs in PD is much greater than in an age-matched population (35). Tau immunoreactive LBs are detected in the medulla of 80% of individuals with sporadic PD or LB dementia (36,37).…”

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confidence: 99%