DEMENTIA DEMENTIA Dr. Ross Alexander Dunne Consultant Old Age - PowerPoint PPT Presentation

DEMENTIA DEMENTIA Dr. Ross Alexander Dunne Consultant Old Age Psychiatrist Dementia Lead, NIHR-CRN:GM Clinical Director GM Dementia Research Centre Honorary Senior Lecturer, University of Manchester Academic Lead Manchester D-TRC 1

WORLD ALZHEIMER WORLD ALZHEIMER REPORT 2018 REPORT 2018 •More people will develop in LMICs •Most research is WEIRD (Western, Educated, Industrialised, Rich, Democracies) •More people are living with dementia than ever, but a smaller proportion of the elderly are developing it in WEIRD countries •50 million people worldwide = Spain / South Korea population 4

5

THE SYNDROME THE SYNDROME THE DISEASES THE DISEASES THE SUBTYPES THE SUBTYPES Classic hippocampal A decline in 2 or more areas of Alzheimer disease Posterior variants cognition below the level Language presentation needed for "normal" (for you) function during everyday living Lewy body disease Movement presentation Cognitive presentation If independence and "normal" function is maintained, but Frontotemporal dementia Language there is objective pen-and- paper impairment then you Behavioural have "Mild Cognitive Vascular dementia Subcortical Impairment" Post stroke 6

DISEASE PROCESSES DISEASE PROCESSES PRIMARY NEURODEGENERATIVE PRIMARY NEURODEGENERATIVE Alzheimer (Amyloid + Tau) Lewy Body (alpha - syn) FTD (Tauopathy) SECONDARY NEURODEGENERATIVE SECONDARY NEURODEGENERATIVE Cerebrovascular disease Infectious (nvCJD) Toxic (Alcohol) - not Korsakoff's 7

DIAGNOSING DEMENTIA DIAGNOSING DEMENTIA Why do people come to clinic? Mandatory stock image of elderly woman staring Symptoms + Insight wistfully out a window Symptoms + problems (for other people) Neuropsychiatric complications of disease Self-neglect Motivation Mood Sleep Mandatory stock image of elderly person’s hands (holding version, note tasteful crochet) 8

https://knightadrc.wustl.edu/cdr/cdr.htm 9 . 1

The CDR is the standard research tool for grading dementia severity. People with a CDR of 0 have no objective cognitive impairment. Those with 0.5 have mild cognitive impairment. What is missing ???? https://knightadrc.wustl.edu/cdr/cdr.htm 9 . 1

Very severe (4) Complete memory loss and poor speech Not oriented to person Unable to speak or only just Bedbound Help eating & toileting Completely physically dependent https://knightadrc.wustl.edu/cdr/cdr.htm 9 . 2

ALZHEIMER DISEASE ALZHEIMER DISEASE 2 PROTEINOPATHIES 2 PROTEINOPATHIES 1. AMYLOIDOSIS AMYLOIDOSIS 2. TAUOPATHY TAUOPATHY 10

ALZHEIMER DISEASE ALZHEIMER DISEASE AMYLOID IMAGING AMYLOID IMAGING 11 . 1

ALZHEIMER DISEASE ALZHEIMER DISEASE TAU IMAGING TAU IMAGING 11 . 2

ALZHEIMER DISEASE ALZHEIMER DISEASE PET - MRI PET - MRI 11 . 3

MILD COGNITIVE IMPAIRMENT MILD COGNITIVE IMPAIRMENT 12 . 1

12 . 2

EARLY DIAGNOSIS IS IMPORTANT EARLY DIAGNOSIS IS IMPORTANT 13

14

MEDIAL TEMPORAL LOBE MEDIAL TEMPORAL LOBE Hippocampus PHG Entorhinal cortex MTA score - marker of neuronal 15 i j

BRAAK AND THE UNITARY HYPOTHESES BRAAK AND THE UNITARY HYPOTHESES Protein folding and aggregation Geographical predeliction Prodromal sequence Protein overlap Gradual Generalisation Mitcohondrial and energy dysfunction Long unmyelinated neurons 16

SURVIVAL SURVIVAL 17

AD V DLB SURVIVAL AD V DLB SURVIVAL 18

PARKINSON'S DISEASE PARKINSON'S DISEASE 19

Coyle-Gilchrist et al 2015 Neurology 20 . 1

Coyle-Gilchrist et al 2015 Neurology 20 . 2

2015 - 2017 PREMATURE DEATHS FROM STROKE 2015 - 2017 PREMATURE DEATHS FROM STROKE 21 . 1

2015 - 2017 PREMATURE DEATHS FROM HEART DISEASE 2015 - 2017 PREMATURE DEATHS FROM HEART DISEASE 21 . 2

DEMENTIA PREVENTION PAR DEMENTIA PREVENTION PAR Prevalence PAR 1000s of cases 21 . 3

22