Australian Association of Gerontology Adelaide, September 22 2015 Neuropathology of old-age dementia University of Cambridge, Institute of Public Health Suvi R. K. Hokkanen, MD MPH srkh2@medschl.cam.ac.uk
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 www.melbournereview.com.au 2/2014
Estimated increase Dementia in percentage prevalence of the 80+ population 30 25 Percentage 20 15 10 Men (%) Women (%) 5 0 65-69 70-74 75-79 80-84 85+ Age group CFAS I, England and Wales, 1989-1993 United Nations, Department of Economic and Social Affairs, Population Division (2011)
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
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 www.melbournereview.com.au 2/2014
Nueuropathology of dementia Kril. Nat Rev Neurol 2009; Spillantini et al. Nature 1997; Ferrer. J Neurol Sci 2010; Alafuzoff. Exp Gernotol. 2012
Bias in pathological studies???
MRC Cognitive Function and Ageing Study (CFAS) - start in 1989-65+ year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle
MRC Cognitive Function and Ageing Study (CFAS) n= 18226 - start in 1989-65+ year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle
MRC Cognitive Function and Ageing Study (CFAS) n= 18226 follow-up - start in 1989-65+ year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle - interviews - cognitive examinations
MRC Cognitive Function and Ageing Study (CFAS) n= 18226 follow-up n= 565 - start in 1989-65+ year olds - Oxford, Ely, Nottingham, Gwynedd, Liverpool, Newcastle - interviews - cognitive examinations - fixed / frozen - CERAD protocol
Neuropathological Diagnosis Prevalence of diagnosis (%) 60 50 40 30 20 10 5 38 38 3 3 4 52 12 0 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
Neuropathological Diagnosis 100 90 13 Prevalence of diagnosis (%) 80 70 60 50 40 30 20 10 0 87 Normal brain 38 62 82 18 87 83 13 17 Insufficient Alzheimer'sParkinson's plaques and tangles disease disease Cortical Lewy bodies 72 28 Insufficient cortical Lewy bodies 58 42 Vascular disease 64 36 Others Dementia No dementia MRC CFAS. Lancet 2001
Neocortical AD pathology and age MRC CFAS. Lancet 2001.
Case report age: 75 80 85 90 95 100 102 MMSE: 29 28 28 25 21 14 medication: antihypertensiva donepezil memantine IADL ADL www.gazettenet.com 12/2014 www.zelmalaceyhouse.com 12/2014
Case report AD type pathology expected in autopsy neurofibrillary tangles neuritic plaques Braak stage CERAD score neuropil threads www. translationalscience.msu.edu 12/2014
Case report Pathological examination: CERAD neuritic plaque score: 0 Braak stage for neurofibrillary tangles: II No significant vascular pathology
Case report Pathological examination: Univ. of British Columbia Neuroanatomy 2/2014 S. Hunter, S. Hokkanen
Old-age hippocampal sclerosis is a cause of dementia Normal CA1 Hippocampal sclerosis (HScl) CA2 CA1 CA3 CA4 CA1 Subiculum S. Hunter
Characteristics of HScl clinical presentation prevalence pathology genetics
Characteristics of HScl Alzheimer s type 46% 27% 9% 9% 9% Alzheimer s type and vascular Vascular Depressive illness prevalence No dementia pathology genetics
Characteristics of HScl 46% 27% 9% 9% 9% Alzheimer s type Alzheimer s type and vascular Vascular Depressive illness No dementia pathology genetics
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
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 214 157 35 8 9 6 χ 2 = 8.30 p= 0.016 allelic frequency C T 0.72 0.28 0.54 0.46 χ 2 = 6.20 p= 0.013
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
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