Pathophysiology of Parkinsons disease Jeremy Cosgrove Consultant - PowerPoint PPT Presentation

Pathophysiology of Parkinson’s disease Jeremy Cosgrove Consultant Neurologist, Leeds Teaching Hospitals

Outline • Who gets Parkinson’s and why? • What is Parkinson’s? • How can we link changes in the brain with the symptoms of Parkinson’s? • What is Parkinson’s disease dementia and how is that different to dementia with Lewy bodies?

Epidemiology Population Incidence Prevalence England 55,997,686 15,465 121,927 UK 66,465,641 18,461 145,519 Population Incidence Prevalence 2025 68,929,547 21,451 168,582 https://www.parkinsons.org.uk/professionals/resources/inci dence-and-prevalence-parkinsons-uk-report 2065 76,898,078 32,303 256,609

Epidemiology • 0.2% of all UK population • 1% of 65 year olds • 4% of 80 year olds • 22 people in a GP practice of 10,000

Risk factors • Advancing age • Male > female 3:2 • Caucasians > Asians and Africans • Family history Kalia and Lang, 2015

Deng et al, 2018

What is Parkinson’s? - Clinical Diagnosis ‘Easy’ Prodrome – before diagnosis ‘Hard’ Kalia and Lang, 2015

Mechanisms causing cell dysfunction Pathological hallmarks: 1) Early degeneration and death of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia 2) α-syn - Lewy body (cell body) and Lewy neurite (axons)

Mechanisms causing cell dysfunction Irwin et al., 2013 Dexter & Jenner, 2013

What is Parkinson’s - Pathological • Stage 1: Medulla • Stage 2: Pontine tegmentum • Stage 3: Midbrain • Stage 4: Prosencephalon and mesocortex • Stage 5 & 6: Neocortex Braak et al, 2003

“Gut-brain axis” Houser & Tansey, 2017

Neurotransmitter pathways Dopaminergic Noradrenergic Serotonergic Cholinergic Haliday at al., 2014

Linking pathology with symptoms Parietal cortex Mild cognitive impairment (MCI) Motor symptoms Frontal Dementia cortex Hallucinations Occipital cortex Prodrome ? Cerebellum Mid-brain Constipation? ? RBD, EDS, Low mood Pons Increased heart rate? ? Medulla Loss of smell Autonomic changes?

Age, hallucination and dementia Reid et al., 2011 Hely et al., 2008

Events heralding the palliative stage Residen&al)care) Visual)hallucina&ons) Falls) Cogni&ve)impairment) Number)of)cases) Age)at)onset) Kempster et al., 2010

Dual syndrome hypothesis Kehagia et al. 2013 Williams-Gray et al., 2009

Complexity of cognitive change in PD Aarsland et al., 2017 Cosgrove et al., 2015

What is PDD and what is DLB? PDD DLB • Impairment in more than one cognitive domain • Representing a decline from premorbid level • Deficits severe enough to impair daily life (social, occupational, or personal care), independent of the impairment ascribable to motor or autonomic symptoms Emre et al., 2007 https://www.lbda.org/go/lbd-spectrum

Pathological spectrum of PDD and DLB Berg et al,. 2014

Conclusions • Alpha-syn is the major pathological driver of PD • Braak model of caudo-rostral spread can link pathology to symptoms • Neurotransmitter dysfunction is common in PD and relates to non- motor symptoms • DLB and PDD are similar entities clinically and part of a disease spectrum

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