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 43% of UK PD Cases Developed PDD 
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Joined: Fri Aug 11, 2006 1:46 pm
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Post 43% of UK PD Cases Developed PDD
This study may be of interest to those dealing with Parkinson's Disease Dementia, which is the name for the disorder when you have parkinsonism symptoms for at least one year prior to developing dementia. Those with Dementia with Lewy Bodies were excluded from the study.

In this study, UK researchers examined the case files of 242 donors with pathologically-confirmed PD. Some of you may know that there is no pathological diagnostic criteria for PD. The criteria used in this Queen Square Brain Bank study was: "depletion of neurons in the substantia nigra pars compacta associated with Lewy bodies in surviving nigral neurones in the context of a compatible clinical picture."

These cases were segregated into earlier disease onset (EDO), tremor dominant (TD), non-tremor dominant (NTD) and rapid disease progression without dementia (RDP). Researchers "found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline."

Researchers found that "of 242 patients, 105 (43%) developed Parkinson's disease-dementia. The mean disease duration to death was 13.8 +/- 5.7 years for those with dementia and 17.0 +/- 7.6 years for those without."

I've copied the abstract below along with some additional excerpts about those who had dementia and the extent to which these cases showed Lewy body pathology.

Robin



Brain. 2009 Sep 16. [Epub ahead of print]

A clinico-pathological study of subtypes in Parkinson's disease.

Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ.
Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College, London, UK.

We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.

PubMed ID#: 19759203 (see pubmed.gov for the abstract only; the full article is available online at a cost of about $50)



Excerpts:

"Forty-six patients had developed dementia within the first 7 years of disease. Patients with the NTD subtype (74%) were significantly over-represented in this group...when compared with TD (24%) and EDO (2%). The mean age at onset of those with early dementia was 68.4 +/- 8.0 years and their mean disease duration was 9.2 +/- 2.9 years. Thirteen (6% of the entire sample) became demented before the age of 65 years. Of these, only one had TD onset, compared with 12 with NTD onset. All four patients with dementia diagnosed before the age of 55 years had the NTD phenotype. Depression was present at the time of diagnosis in 23% of patients with early dementia, which was no different to the percentage in all other cases."

"Alzheimer pathology was significantly more prevalent in the early dementia group. It was present in 71%, though it was of low grade (Braak & Braak Stages I­-II) in more than half; 21% had Braak & Braak Stage III­-IV pathology and two cases (14%) had Braak & Braak Stage V­-VI."

"To examine the extent to which pathology predicts clinical features, we compared pathological grades with clinical groups. We dichotomized patients according to the extent of Lewy body pathology as follows: brainstem/limbic disease (Lewy body score 1­7); and neocortical disease (Lewy body score >7). There was a significant difference in the subtype make-up of these two classes. Patients with brainstem/limbic Lewy body scores were more likely to be EDO or TD and those with neocortical Lewy body disease were more likely to be NTD, while RDP was approximately equally represented in each."

"Although it is recognized that the pathology represents the end stage of disease, and may not be representative of the dynamic processes that evolve during decades of illness, it is instructive that the end-stage Lewy body pathology itself does appear to predict certain clinical characteristics. Most striking were the findings that patients with neocortical Lewy body disease were much more likely to have a NTD phenotype, and those with brainstem/limbic pathology were more likely to have EDO or TD phenotypes. In our study, the main clinical correlations of Lewy body scores were bradykinetic onset and cognitive dysfunction."


Fri Sep 18, 2009 10:29 pm
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Joined: Fri Jun 19, 2009 11:23 am
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Robin
After reading your post I started to wonder if my LO has PDD because he had hand tremors a year before the dementia. I did some more searching and found this on eMedicineHealth.com about Parkinson's Disease Dementia. ( I did a copy/paste)

"The anticholinergic drugs, for example, help balance levels of dopamine and acetylcholine, another neurotransmitter, in the brain. These drugs can improve movement disorders but often make memory loss worse. "

I recently asked the question if Aricept helped tremors because my LO's hand tremors are gone, although he still has the very slow gait and the mask like expression.

Just a thought. We see the neurologist at the end of the this month and maybe that would be a good question for him.

Just wanted to let you know I found that study interesting (the parts I could understand)
Mary


Sat Sep 19, 2009 2:31 pm
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Location: SF Bay Area (Northern CA)
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The key word in what you excerpted is "anticholinergic." Aricept is NOT anticholinergic. I guess you could think of Aricept is PRO-cholinergic.


Sat Sep 19, 2009 4:22 pm
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