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Kognitiva störningar vid Lewy-kroppsjukdommar

Kognitiva störningar vid Lewy-kroppsjukdommar

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Kognitiva störningar vid Lewy-kroppsjukdommar

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  1. Kognitiva störningar vid Lewy-kroppsjukdommar Dag Aarsland Alzheimer’s Disease Research Centre, NVS, Karolinska Institutet Sentrum för åldersrelaterade sjukdommer, Stavanger Universitetssjukhus

  2. Översikt • Kogitiva störningar vid Parkinson: • Epidemiologi • Mekanismer • Behandling • Lewykroppsjukdom • Klinik • Diagnostik • Behandling

  3. Point-prevalence: 25-30% Frequency of dementia in PD Cumulative prevalence 80% The Sydney Study. Hely et al. 2008 Mov Disord 2005; Arch Neurol 2003; Neurol 2008

  4. Mild cognitive impairment (MCI) in PD

  5. Not if, but when! Wide variation in time from onset of PD to dementia N=576 Proportion without dementia Years after onset PD Aarsland; Marder et al. J Neurol 2007 Time to «inflexion point» Mov Disord 2011

  6. PD- MCI predicts dementia C. Janvin et al. Mov Disord. 2006 Sep;21(9):1343-9

  7. Predictors of cognitive decline in the CamPaign study Variation in rate of decline: Williams-Gray 2007

  8. Potential Brain changes underlying cognitive decline in PD • Structural: • Limbic and neocortical Lewy bodies • Amyloid plaques • Synaptic / neuronal loss • Cerebrovascular disease • Inflammation • Neurotrophic factors • Neurotransmitters: • Noradrenaline (attention, vigilance) • Dopamine (working memory, executive f) • Acetylcholine (attention, memory, etc) • Glutamate?

  9. Lewy bodies Plaques

  10. Brain changes associated with PD-MCI • PET-VBM: Reduced metabolism in prefrontal/parietal cortex (Pappata Neurol 2011) • pET: CHolinergic deficit (Shimada 2009) • MRI: Cortical atrophy (Beyer 2006) • CSF: Low abeta42 (Alves 2010)

  11. Behandling

  12. Cholinesterase inhibitors in PD: Systematic review Cholinesterase inhibitors Memantine Some case series 3 RCT • 20 studies identified: • Donepezil 11 • Rivastimine 6 • Galantamine 2 • Tacrine 2 • Design: • Open label 11 • Case series 2 • RCT 6 • 4 small < 40 • 2 large > 500 Van Laar et al. 2010.

  13. Cochrane meta-analysis: Effect of ChEIs on MMSE in PDD/DLB Rolinski M, Fox C, Maidment I, McShane R. Pubished Online March 14, 2012

  14. Drop-out: Riv 27.3% vs Pla 17.9%

  15. Memantin for PDD/DLB: Meta-analyse Ballard, Emre, Aarsland. Work in progress