Neuropathology of old-age dementia

Transcription

1 Australian Association of Gerontology Adelaide, September Neuropathology of old-age dementia University of Cambridge, Institute of Public Health Suvi R. K. Hokkanen, MD MPH

2 Dementia types Alzheimer s dementia Dementia with Lewy Bodies Vascular Dementia Frontotemporal dementia Dementia in Parkinson s Disease Mixed Other? Alzheimer s and Vascular Dementia 2/2014

3 Estimated increase Dementia in percentage prevalence of the 80+ population Percentage Men (%) Women (%) Age group CFAS I, England and Wales, United Nations, Department of Economic and Social Affairs, Population Division (2011)

4 Challenges of dementia diagnosis in the older old Cognitive decline viewed as normal aging Comorbidities, medications Lack of normative neuropsychological data Limitations of standard diagnostic criteria

5 Dementia in the oldest old Alzheimer s dementia Dementia with Lewy Bodies Vascular Dementia Frontotemporal dementia Dementia in Parkinson s Disease Mixed Other? Alzheimer s and Vascular Dementia 2/2014

6 Nueuropathology of dementia Kril. Nat Rev Neurol 2009; Spillantini et al. Nature 1997; Ferrer. J Neurol Sci 2010; Alafuzoff. Exp Gernotol. 2012

7 Bias in pathological studies???

8 MRC Cognitive Function and Ageing Study (CFAS) - start in year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle

9 MRC Cognitive Function and Ageing Study (CFAS) n= start in year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle

10 MRC Cognitive Function and Ageing Study (CFAS) n= follow-up - start in year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle - interviews - cognitive examinations

11 MRC Cognitive Function and Ageing Study (CFAS) n= follow-up n= start in year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle - interviews - cognitive examinations - fixed / frozen - CERAD protocol

12 Neuropathological Diagnosis Prevalence of diagnosis (%) Normal brain Insufficient plaques and tangles Alzheimer's disease Parkinson's disease Cortical Insufficient Lewy bodies cortical Lewy bodies Vascular disease Others MRC CFAS. Lancet 2001

13 Neuropathological Diagnosis Prevalence of diagnosis (%) Normal brain Insufficient Alzheimer'sParkinson's plaques and tangles disease disease Cortical Lewy bodies Insufficient cortical Lewy bodies Vascular disease Others Dementia No dementia MRC CFAS. Lancet 2001

14 Neocortical AD pathology and age MRC CFAS. Lancet 2001.

15 Case report age: MMSE: medication: antihypertensiva donepezil memantine IADL ADL 12/ /2014

16 Case report AD type pathology expected in autopsy neurofibrillary tangles neuritic plaques Braak stage CERAD score neuropil threads www. translationalscience.msu.edu 12/2014

17 Case report Pathological examination: CERAD neuritic plaque score: 0 Braak stage for neurofibrillary tangles: II No significant vascular pathology

18 Case report Pathological examination: Univ. of British Columbia Neuroanatomy 2/2014 S. Hunter, S. Hokkanen

19 Old-age hippocampal sclerosis is a cause of dementia Normal CA1 Hippocampal sclerosis (HScl) CA2 CA1 CA3 CA4 CA1 Subiculum S. Hunter

20 Characteristics of HScl clinical presentation prevalence pathology genetics

21 Characteristics of HScl Alzheimer s type 46% 27% 9% 9% 9% Alzheimer s type and vascular Vascular Depressive illness prevalence No dementia pathology genetics

22 Characteristics of HScl 46% 27% 9% 9% 9% Alzheimer s type Alzheimer s type and vascular Vascular Depressive illness No dementia pathology genetics

23 Characteristics of HScl 46% 27% 9% 9% 9% Alzheimer s type Alzheimer s type and vascular Vascular Depressive illness No dementia Prevalence of TDP-43 genetics

24 Characteristics of HScl 46% 27% 9% 9% 9% Alzheimer s type Alzheimer s type and vascular Vascular Depressive illness No dementia Prevalence of TDP-43 non-hscl HScl statistic GRN rs5848 genotype, n CC CT TT χ 2 = 8.30 p= allelic frequency C T χ 2 = 6.20 p= 0.013

25 Take-home messages With increasing age, dissociation of clinical and pathological findings With increasing age, more mixed pathology Population-based clinicopathological studies are an invaluable research resource HScl presents clinically similar to AD, but associates pathologically with TDP-43

26 Thank you! University of Cambridge: Prof Carol Brayne Ms Sally Hunter Dr Fiona Matthews Dr Thais Minett University of Sheffield: Prof Paul Ince Prof Stephen Wharton Newcastle University: Dr Tuomo Polvikoski University of South Australia: Dr Hannah Keage University of Helsinki: Dr Liisa Myllykangas Ms Anna Raunio Ms Mia Kero