Degenerative Dementias: MRCPsych Course Dr Chris Davison, Consultant Old Age Psychiatrist Content • Dementia • Cases • Exams • Images 2 Aims • Describe the clinical presentation and course of the common degenerative dementias of late life, particularly AD and DLB • Introduce the concept of mild cognitive impairment as a possible early presentation of dementia • Encourage the use of operationalised diagnostic criteria for these disorders • Raise awareness of less common causes of degenerative dementia that may be encountered in the practice of old age psychiatry 3 Learning Outcomes • Be able to diagnose the dementia syndrome and aetiological subtypes, using systematic methods and with an awareness of the probable diagnostic accuracy • Understand the issues around diagnosing dementia at an early stage and to know the approach to assessment that will best assist in this. • Understand the specific importance of accurate diagnosis for optimal management of each of the common disorders 4 What is dementia? 5 What is dementia? Clinical syndrome with multiple and persisting cognitive impairments Memory plus other cognitive functions affected Impairment lasting 6 months Functional impairment in daily living e.g. repetitive questions, inability to make a cup of tea, putting clothes on wrong Exclusion of other conditions interfering with cognitive function Depression Delirium Hypothyroid etc. 6 What is dementia? Executive function Impaired decision making, apathy Memory plus other cognitive visuo neglect,Spatial functions affected Space perception impairment, agnosia impairment, Memory - Functional constructive impairment or Language & motor Aphasia, Alexia, Apraxia, Apraxia, Alexia, Aphasia, decline from premorbid function Visual function Agnosia, Prosopagnosia 7 What is dementia? Can be progressive e.g. Alzheimer's dementia Can be static e.g. secondary to head injury 8 What is dementia? Degenerative Dementia in old age is huge problem Risk doubles every five years over age of 65 800,000 people in UK affected by dementia Numbers set to grow significantly – 1 million by 2021 Costs 17 billion pounds 9 DSM 5 DSM 5: Dementia = Major Neurocognitive Disorder 10 Dementia prevalence Dementia prevalence in the UK 11 Causes of Dementias Parkinsons Disease Fronto-temporal dementia dementia Dementia with Lewy Bodies Alzheimer’s Huntingtons disease disease Mixed dementia Vascular dementia Rare causes 12 Progressive Dementias Alzheimer's Disease 50% Mixed Other Causes Alzheimer's/ 10% Vascular Disease 10% Vascular Disease Dementia with 10% Lewy Bodies 20% 13 Case study • 69 year old lady • 3 year history of progressive worsening of short term memory • On a couple of occasions put electric kettle on gas hob • Keeping out of date food in fridge and missing appointments • On clinical assessment: • MMSE 22/30. Mood apathetic and some depression • Experienced musical hallucinations. Doesn’t think memory is that bad. • Physically well otherwise 14 Case study • 81 year gentleman • 1 year history of progressive worsening of short term memory • Nominal aphasia - mild • On clinical assessment: • MMSE 19/30. Reduced verbal fluency. • High BP – but treated • Mild MI when 74 • History of prostate cancer • Physically slightly stooped. No focal neurological signs. • At research clinic has CSF sample – high tau and low beta amyloid 15 16 AD: NINCDS-ADRDA criteria Dementia established by clinical examination and cognitive examination e.g. MMSE Deficits in two or more areas of cognition Progressive worsening of memory / other cognitive functions No disturbance of consciousness Onset between 45 and 90 (most often >65) No systemic or other brain disorders which could account for progressive cognitive deficits McKhann et al. Neurology 1984;34:939-944. AD: NINCDS-ADRDA criteria Supported by Impaired activities of daily living or altered behaviours Family history of Alzheimer’s Cerebral atrophy on CT head scan and progressive atrophy noted with serial scans or normal CT McKhann et al. Neurology 1984;34:939-944. AD: NINCDS-ADRDA criteria Other clinical features Plateaus in course of progression Associated behavioural and psychological symptoms Depression Insomnia Incontinence Delusions Hallucinations Verbal, emotional or physical outbursts Weight loss Neurological signs (especially advanced AD) Increased muscle tone, myoclonus, gait disorder, seizures McKhann et al. Neurology 1984;34:939-944. Timeline of neuropathology and symptoms in AD Alzheimer’s Dementia Brain changes in Alzheimer’s dementia Normal Alzheimer’s Widened sulci Alzheimer’s Dementia Brain changes in Alzheimer’s dementia Hippocampus – memory function Normal Alzheimer’s Biomarkers in AD Biomarkers in AD Brain changes in Alzheimer’s dementia Normal Mild Increasing hippocampal atrophy Moderate Severe Biomarkers in AD Neuroimaging Structural PET – metabolism (FDG) and amyloid load (PIB) Biomarkers in AD CSF sampling High total tau High phosphorylated tau Low beta amyloid (A-Beta40 and A-Beta42) Predictive of Alzheimer’s Biomarkers in AD Proposed new diagnostic criteria for AD ADD Workgroup, McKhann et al, Alzheimer’s and Dementia, 2011 • Probable AD: • Dementia (amnestic or non-amnestic presentation) • Gradual onset • Evidence decline/ progression • No related stroke/ CVD on imaging/ presence of DLB/FTD etc • Probable AD with evidence of AD pathological process: • Evidence neuronal injury (MRI, FDG PET, CSF tau) • Alterations in A-beta (Amyloid PET or CSF) • AD like profile (history and course) • Possible AD with evidence of AD pathological process: • Meet criteria for another dementia but AD biomarker positive • Pathophysiologically proved AD: • Meet clinical criteria and autopsy positive Case study 2 • 69 year old lady • 1 year history of subjective worsening of short term memory • Forgetting appointments and needs to write things down to remember. • On clinical assessment: • MMSE 27/30 • Intact activities of daily living • Physically well otherwise Research amyloid scan Research PET FDG scan Mild Cognitive Impairment Petersen et al. 1999,2004 Mild Cognitive Impairment • Definition – Memory complaint by patient, family or physician – Normal activities of daily living – Essentially preserved general cognitive abilities – Objective impairment of cognitive function (> 1.5 or 1.0 SD of age mean i.e. 7% or 16% of normal population) – Clinical dementia rating score of 0.5 – Not clinically demented Petersen et al. 1999,2004 Mild Cognitive Impairment • Yet another in a long line of attempts to define a subclinical syndrome • However gained much wider acceptance Petersen et al. 1999,2004 Strengths of MCI concept – Significant research evidence supporting it as a syndrome – Requires objective element to assessment – Relies on a holistic and in-depth clinical assessment and not just a cognitive cut-off – Other criteria been applied loosely – Provided basis for predicting progression to dementia – Focus of major randomised controlled trials Areas of controversy • Normal or abnormal aging – absent minded or in the early stages of dementia • Definition • Validity • Reliability • Prognosis • Pathological basis Limitations with the MCI concept Farias et al 2009; Petersen et al. 2009 Limitations with the MCI concept Instability of diagnosis over time E.g. Ritchie et al 50% of MCI return to normal after 1 year. But likely related to education, psychiatric co-morbidity (depression), medications, hormonal changes and genetics Reliability varies with setting & retrospective surveys However prospective studies provided more stable estimates Farias et al 2009; Petersen et al. 2009 Progression In Memory Clinic/Hospital samples Progression to dementia: 10 – 15 % / year Stable over time, few recover Higher prior probability of having underlying disorder In population Progression to dementia: 6 – 10 % / year More unstable with people becoming “cognitively normal” again Broader spectrum of MCI severity and more heterogeneity Farias et al 2009; Petersen et al. 2009 MCI Subtypes People with MCI are probably at greater risk of progressing to Alzheimer’s disease if: • they are older • they have a family history of dementia • they have had high blood pressure • they have high cholesterol • they have a risk gene (ApoE4) Biomarkers in AD Case study • 63 year old retired physics teacher • Complaining of blurring of vision and seeing lights, with a normal ophthalmic examination • CT head was normal • She re-attended one year later complaining of subjective short term memory difficulties and “bumping into things”. Struggling to dress herself and gets easily confused • On examination, no neurological signs • MMSE 22/30. Deficits in visuo-spatial, writing, calculation and following command. Memory intact • Has finger agnosia, left-right disorientation Posterior cortical atrophy • Atypical variant of AD • Also called Benson's syndrome • Characterised by posterior atrophy • Affects occiptial and parietal lobe areas • Tend to have well preserved memory and language • However often progressive, dramatic and relatively selective decline in vision and/or literacy skills such as spelling, writing and arithmetic • Can present with Gerstmann’s syndrome • Dysgraphia/agraphia: deficiency in the ability to write • Dyscalculia/acalculia: difficulty in learning or comprehending mathematics • Finger agnosia: inability to distinguish the fingers on the hand • Left-right disorientation • Can also present with Prosopagnosia • Also Balint’s syndrome • inability to perceive the visual field as a whole