Dementia: from prevention to cure

1. Dementia: from prevention to cure Christopher Patterson McMaster University, Hamilton, Ontario Canada

2. Objectives • Define dementia • Describe epidemiology of dementia in India • Distinguish the common types of dementia • Describe “standard” investigation of suspected dementia • Introduce principles of management • Touch on future trends

3. Dementia: A syndrome • An acquired disorder • Diffuse cognitive deficits: memory (usually) aphasia, apraxia, agnosia, executive dysfunction • Deficits sufficient to interfere with daily function • Not occurring solely in delirium or depression CMAJ 1999;160 (12 suppl)

4. Prevalence of dementia in India • Low estimate 1.9% over age 65(Ferri C et al Lancet 2005; 366: 2112) • Higher estimate 2.7% over age 65 (Kalaria R et al Lancet Neurology 2008; 7:812)

5. Highest estimate of prevalence: Kerala India • Door to door survey • Screen with MMSE • Full assessment if < 23 Shaji S et al Br J Psychiatr 2005; 186: 136

6. Global burden of Dementia10/66 Dementia Research Group

7. Risk Factors for Alzheimer’s disease • Age • Family history • Lifestyle Physical exercise Mental exercise Diet Tobacco Head injury • Hypertension • Elevated serum cholesterol • Elevated serum homocysteine

8. Risk Factors for Alzheimer’s disease

9. Risk Factors for Alzheimer’s disease

10. Can we predict who will develop dementia? Knowing the following risk factors in middle age a calculation of future likelihood of dementia: • Age • Level of permits education • Systolic BP • BMI • Total serum cholesterol • Degree of physical activity Patterson C et al CMAJ 2008; 178:548

12. Calculating future riskPatterson C et al CMAJ 2008; 178:548

13. Types of Dementia • Alzheimer’s • Mixed • Lewy-body • Frontotemporal • Vascular • Other neurodegenerations (e.g.Huntingdon’s) • Infections (e.g. HIV,Jakob-Creutzfeld)

14. Types of Dementia • Alzheimer’s • Mixed ► 80% of all dementias • Lewy-body • Frontotemporal • Vascular • Other neurodegenerations (e.g.Huntingdon’s) • Infections (e.g. HIV,Jakob-Creutzfeld)

15. Interactions Between Vascular Dementia and Alzheimer’s Disease AD Mixed VaD 80% of all Dementias

17. The Nun Study • Longitudinal study of the Teaching Sisters of Notre Dame (USA) • 678 enrolled since 1991 aged 75-102 • Written autobiographies within 2 years of entry • Annual cognitive testing • Brain autopsies • 400 deceased by 2003 Snowdon DA Ann Intern Med 2003;139: 450

18. The Nun Study • Early linguistic ability predicts later dementia • Severity of Alzheimer changes (amyloid plaques, neurofibrillary tangles) did not always correlate with cognitive changes • Presence of stroke (especially small WM) increased clinical dementia (RR=20)

19. The Nun Study: pathology of those with dementia Alzheimers alone 43% Mixed (AD + strokes) 34% Other types of pathology 20% Vascular alone 2.5%

20. Pure vascular dementia is relatively rare • Several clinicopathological studies • Vascular dementias suspected commonly in life • At autopsy, vascular pathology alone rarely explained clinical features • Mixed pathology common • BUT may be more common in Asian counties

21. Functional Autonomy Cognitive Function Motricity (Motor Function) Behaviour Problems Mood Symptomatic Domains of AD Over Time Deterioration Time Adapted from Gauthier et al. Clinical Diagnosis and Management of Alzheimer’s Disease, 1999.

23. Natural History of AD Severe Early diagnosis Mild-to-moderate 30 Symptoms 25 Diagnosis 20 Loss of functional independence 15 Mini-Mental State Examination (MMSE) Behavioural problems 10 Nursing home placemen t 5 Death 0 1 2 3 4 5 6 7 8 9 Time (years) Reproduced with permission from Feldman and Gracon, 1996.

24. Alzheimer’s Disease Progresses Through Distinct Stages Average duration 7-10 years Mild Moderate Severe Stage Symptoms • Memory loss • Language problems • Mood swings • Personality changes • Diminished judgment • Behavioural, personality changes • Unable to learn/recall new information • Long-term memory affected • Wandering, agitation, aggression, confusion • Require assistance w/ADL • Gait, incontinence, motor disturbances • Bedridden • Unable to perform ADL • Placement in LTC needed

25. Alzheimer’s disease anatomical correlates: 3 phases of illness • Limbic system: memory • Parietal: spatial organization, function • Frontal: behaviour

26. Cholinergic Pathways From theBasal Forebrain PC FC BF OC H

27. Frontotemporal Dementia

28. Frontotemporal dementia 3 clusters of features: (a) Behavioural (disinhibition, apathy, poor insight and judgement) (b) Language (progressive expressive type aphasia, contraction of language) (c) Self neglect First described by Arnold Pick

29. Frontotemporal dementia • Familial in 50% • Serotoninergic (vs. cholinergic) deficit • Memory not a prominent feature until late • Often difficult to manage

30. Lewy (or Lewey) body dementia Also known as: • Dementia with Lewy bodies • Lewy body dementia

31. Lewy body dementia Core features (2 probable, 1 possible): • Fluctuating cognition • Recurrent well formed detailed visual hallucinations • Spontaneous Parkinsonism Suggestive features (1 possible, 1 plus above, probable: • REM sleep disorder • Severe neuroleptic sensitivity McKeith I, et al Neurology 2005; 65: 1863

32. Lewy body dementia Supportive features: • Repeated falls • Systematized delusions • Dementia occurs before or concurrently with Parkinsonism • Early visuospatial dysfunction • May progress more rapidly than AD

33. Lewy body dementia • Severe cholinergic deficit • Anti Parkinsonian medications may worsen psychosis • Antipsychotic agents may worsen Parkinsonism • Cholinesterase inhibitors often work well

34. Vascular dementia • Dementia follows in wake of stroke • Presentation will depend upon location and size of stroke • Clear history of stroke not always present • Large overlap with Alzheimer’s disease (i.e. mixed dementia)

35. Brain Imaging of Vascular dementia 3 Types of VaD Multiple large vessel infarcts Bilateral strategic thalamic infarcts Binswanger’s disease Source: Stephen Salloway, MD

36. Assessment of Dementia: domains • Cognitive • Functional • Behavioural • Affective

37. 80 year old lady • Brought to you by only daughter • Forgot daughter’s birthday this year • Missed payment of several bills • Housework and personal hygiene slipping slightly

38. 80 year old lady: history

39. 80 year old lady: history • Onset and duration • Focal neurological symptoms • Precipitating events • Past history and risk factors • Social history and risks (fire, wandering, summoning help, low TI medications) • Medications (all of them) • Order lab tests?

40. 80 year old lady: examination

41. 80 year old lady: examination • Overall appearance (e.g. cleanliness, grooming, trauma, clothing) • General physical ( e.g. HF, hypoxia, thyroid, tumours) • Focal neurological signs • Gait, balance

42. 80 year old lady: mental status

43. 80 year old lady: mental status • MMSE or equivalent • Clock drawing • Montreal Cognitive Assessment (MoCA) • Measures of insight & judgement

44. 80 year old lady: laboratory

45. 80 year old lady: laboratory • CBC • Blood sugar • Electrolytes • TSH • B12 • Calcium

46. 80 year old lady: neuroimaging

47. 80 year old lady: neuroimaging • Age under 65 • Focal neurological symptoms • Focal neurological signs • Short history • Head trauma • Anticoagulants or bleeding • Malignancy that might metastasize • Atypical features i.e. not suggesting AD

48. 80 year old lady: management

49. 80 year old lady: management • Disclosure • POA, advance directives • Risk assessment (consider OT) • Transport • Education and support • Alzheimer’s Society or other support organization • Case manager • Education sessions • Medications

50. AD Caregiver Time by Disease Severity Hux et al. CMAJ, 1998.