Dementia & Primary Care

1. Dementia & Primary Care Dr. Robert Tobiansky (Barnet Consultant) Dr Jonathan Hare (Enfield Consultant) Dr. Michael Payne (Haringey Consultant) Barnet, Enfield & Haringey Mental Health Trust

2. Overview of clinical aspects of Dementia • Definition & prevalence of Dementia • Differential Diagnosis • Management & investigations • the role of medication, including ACHEIs • Management as a GP • Community services • Medico-legal issuesConsent & Capacity

3. National Dementia Strategy Published 2 Feb 2009 • Five year plan • 17 interlinked objectives • £150 million extra funding Four key themes • Improving awareness • Early better diagnosis • Improved quality of care • Delivering the Strategy

4. Objectives of the National Dementia Strategy

5. Dementia care pathway Primary care Social care Specialist older people’s mental health services Help seeking DIAGNOSIS specialist care Social care community & care homes Primary Care Acute Trusts Peer & Vol. Sector Support 1. Encourage help seeking and referral 2. Locate responsibility for early diagnosis and care 3. Enable good quality care tailored to dementia

6. DEMENTIA: DEFINITION

7. Dementia A syndrome due to disease of the brain usually of a chronic or progressive nature • Multiple disturbances of higher cortical function • Global impairment: intellect, memory, personality • Changes in emotional control, social behaviour, motivation • In clear consciousness • Decline in usual functional abilities

8. EPIDEMIOLOGY OF DEMENTIA: • Nature Reviews Neurology • Reitz et al 2011

9. Epidemiology of Dementia: • Global prevalence 24 million predicted to double every 20 years to 2040 • 5% over 65 years • 20% over 80 years • Over 65 years - prevalence doubles every 5 yrs • Annual incidence c. 9 / 1000 population

10. Dementia: key points • Prevalence increases with older age • rare in < 65, if suspect in younger patient refer to neurologist • diagnosis based on History, Physical & mental state examination & routine investigations

11. DEMENTIA: COMMONEST TYPES

12. Dementia Many causes but commonest are: • Alzheimer’s Disease • Vascular Dementia • Lewy Body Dementia • Alcohol related dementia • Frontotemporal dementia

15. Alzheimer’s Disease: Neuropathology • Atrophy, widened sulci, shrunken gyri • Amyloid plaques: extracellular, swollen neuronal processes with core of amyloid-b(Ab) • Neurofibrillary tangles (NFTs): intracellular, hyperphosphorylated Tau (microtubule assembly protein) forms insoluble aggregates = PHF • Widespread loss of neurones & synapses • Granulovacuolar degeneration • Gliosis, loss of dendrites • Hirano bodies (eosinophilic, cigar shaped)

16. AD: Neurochemical changes • Best described: diminished Acetyl-Choline, CAT, cholinergic neurones (Basal n. Meynert) • Also reduction in GABA, NA, 5HT etc

17. Risk Factors for AD: • Age • Family History (genes on chromosome 21, 14, 1, 19) • Down’s Syndrome • Head injury • Limited education • Risk factors for Vascular Dementia (Diabetes, hypertension, obesity, AF, lipids etc)

18. AD Genetics 1: Young-onset • Familial Alzheimer’s Disease - autosomal dominant, small minority, young onset, APP mutations • Ch21: beta amyloid precursor protein gene • Ch14: presenilin 1 gene • Ch1: presenilin 2 gene • All lead to Ab aggregation (increased Ab42) imbalance between Ab production & clearance

19. AD Genetics 2: late onset • Non-Mendelian AD • great majority of cases • genetic + environmental factors • first degree relatives of late-onset AD patients have 2x expected lifetime risk • Ch19: apolipoproteinE; lipid binding protein in 3 isoforms e2; e3; e4 1x e4 = 2-3 fold increase in AD risk 2 x e4 = 5 fold increase in AD risk Lowers age of onset by 7 years

20. AD Genetics 2: late onset • Various other genes implicated with weaker effects, all thought to involve increased Ab42 e.g: • Sortilin-related receptor 1 gene (SORL1) • Clusterin gene (CLU) • Complement receptor type 1 gene (CR1) • Phosphatidylinositol-binding clathrin assembly protein (PICALM) gene

21. Biomarkers for AD • Contribute to increased specificity of diagnosis • In AD CSF levels of Ab42 lower (less soluble) • CSF elevated total TAU & Phosphorylated Tau • Total Tau levels increase with AD progression • Structural MRI: medial temporal lobe atrophy

22. Vascular Dementias • Includes Multi Infarct Dementia • Single strategic infarct • Subcortical VAD (Binswangers) / SVD • Hypoperfusion Dementia • Specific Arteriopathies (eg CADASIL)

23. NINDS-AIREN Criteria for VaD(Roman et al, 1993) • Dementia (memory and 2 or more domains) • Cerebrovascular disease (focal neurology and CVD on brain imaging) • Link between the 2 (3 months or abrupt/fluctuating clinical course) • PossibleVaD if brain imaging negative or relationship (3/12) not clear

24. NINDS Neuroimaging Criteria for VaD • Topography • Large vessel strokes • Extensive white matter change • Lacunes (frontal/basal ganglia) • Bilateral thalamic lesions • Severity • Large vessel lesion of dominant hemisphere • Bilateral strokes • WML affecting >25% white matter (Price et al, 2005)

25. VAD: Neuropathology: • Micro – infarcts • Cystic necrosis of infarcted areas • Reactive gliosis • Patches of demyelination of white matter

26. Risk Factors for VAD: • Old Age • Family history • Male sex • Geography & race • Hypertension • Smoking • Diabetes • Cardiac arrhythmia • Hyperlipidaemia •  Increased homocysteine

27. Hachinski Ischaemic Score: • Abrupt onset (2) • Stepwise deterioration (1) • Fluctuating course (1) • Nocturnal confusion (1) • relative preservation of personality (1) • Depression (1) • Somatic complaints (1) • Emotional incontinence (1) • History of hypertension (1) • History of strokes (2) • Evidence of atherosclerosis (1) • Focal neurological symptoms (2) • Focal neurological signs (2) • < 4 suggests AD > 7 suggests VAD

28. Dementia with Lewy Bodies • a progressive degenerative brain disease • shares symptoms - and sometimes overlaps - with Alzheimer’s and Parkinson’s

29. Dementia with Lewy Bodies • Lewy Body = smooth round intraneuronal inclusion bodies • LBs throughout cortex, midbrain or brainstem • “abnormal protein structures” first described in 1912 by Frederich Heinrich Lewy

30. Criteria for Probable DLB McKeith et al, Neurology, 2005 • Cognitive decline sufficient to interfere with social/occupational function • CORE features (at least one core + one suggestive or 2 core features must be present): - Fluctuation - Recurrent visual hallucinations - Spontaneous parkinsonism • Suggestive features: - REM sleep behaviour disorder - Neuroleptic sensitivity - Dopaminergic abnormalities in basal ganglia on SPECT/PET

31. Features supportive of the Dx of DLB are: • Repeated falls • Syncope • Transient loss of consciousness • Neuroleptic sensitivity • Systematized delusion • Hallucinations in other modalities auditory, olfactory or tactile

32. DEMENTIA: GENERAL SIGNS & SYMPTOMS

33. Dementia: general signs & symptoms • Early stages: • memory impairment, loss of planning, judgement, difficulty with administrative tasks etc • Intermediate • impaired basic ADL can’t learn new information, increasing disorientation time & place • increased risk of falls and accidents due to confusion and poor judgment

34. Dementia: signs & symptoms • Severe dementia: no ADL skills, totally dependent for feeding, toileting, & mobilising. Severe global cognitive impairment • risk of malnutrition and aspiration • poor mobility & malnutrition increases risk of pressure sores • Seizures, dehydration, malnutrition, aspiration, pressure sores • death from infection (resp., skin, UTI etc)

35. Dementia: signs & symptoms • Behavioural problems (BPSD): • Persecutory delusions, suspiciousness in c. 25% • wandering, aggression, agitation • Depressive symptoms in c. 60% • Depression in c. 25%

36. Dementia: Diagnosis & Investigations • A clinical diagnosis • History from an informant • Physical examination • Medication review • Mental state examination & cognitive assessment (AMT or MMSE) • Bloods: FBC / ESR / U+E / LFT / TFT / Glucose / Ca + Po / B12 + Folate / +/-Treponema serology • CXR, ECG

37. Additional investigations: • If indicated from history & examination: • CT: cortical atrophy, widened ventricles in AD. Evidence of vascular disease in VAD. Exclude SOL • MRI: v. sensitive for VAD • SPECT valuable in differentiating AD, VAD, FTD (DAT scan for suspected DLB) • EEG (non-specific diffuse slowing of alpha rhythm. Delta & theta activity • psychometric testing if unusual presentation or uncertain

38. NICE/SCIE Guidelines for Dementia 2006 • MRI is preferred modality, CT can be used • Structural imaging should be used to exclude other cerebral pathologies & help establish subtype • HMPAO SPECT can be used to help differentiate between AD, VaD and FTD if diagnosis is in doubt • FP-CIT SPECT should be used to help establish • The diagnosis of DLB if the diagnosis is in doubt

39. Additional investigations • Increasing recognition of value of CSF biomarkers CSF-tau & CSF-Aß42 as Diagnostic Markers for Alzheimer Disease • thesebiomarkers may have a role in the clinical workup of patientswith cognitive impairment, especially to differentiate earlyAD from normal ageing • low CSF β-amyloid 1-42, high total tau protein, and elevated phosphorylated tau181P predict AD

40. Management of Dementia: • Treat medical disorders & any causes of disability (mobility, vision, hearing etc ) • Treat BPSD: depression, psychosis, behaviour disturbance • Assess ADLs and maximise function, assess risk (occupational therapist) • Finances: LPOA, COP, testamentary capacity, benefits (attendance allowance), council tax exemption (social worker), • Early referral to social services (do not wait for secondary care)

41. Management of BPSD in Dementia: (Iliffe) • P: Physical: pain, infection, constipation • A: Activities of others: misinterpretation • I: Intrinsic to dementia: walking, pacing activity • D: Depression or delusions

42. Management of dementia: • Home alone with support from social services: • Home with care package eg. carer for personal & domestic care, meal preparation, shopping, cleaning, etc. supervise medication • Meals on wheels • Day centre to increase socialisation & stimulation

43. Management of Dementia: • Support for carers:Alzheimer’s Society / Age Concern / BCAS advice & support groups • Respite care • DHTT if acute severe behavioural problems • Higher prevalence of depression & anxiety in carers • Alternatives to home care (dependency & risk): extra care sheltered housing, residential & nursing homes • NHS continuing care funding

44. Management of Dementia: Medication • Medication for cognitive impairment (cognitive enhancing drugs) • Medication for BPSD

45. Management of Dementia: Medication • Anti-dementia drugs: - Cholinesterase inhibitors: (Approved by NICE) Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Reminyl) - Memantine (Ebixa) (approved by NICE for severe Dementia March 2011)

46. Cholinesterase Inhibitors: • Cholinesterase inhibitors for Alzheimer's disease  Birks Cochrane Database of Systematic ReviewsThe three cholinesterase inhibitors are efficacious for mild to moderate Alzheimer's disease. Despite the slight variations in the mode of action of the three cholinesterase inhibitors there is no evidence of any differences between them with respect to efficacy.

47. Memantine (Ebixa) • Memantine for dementiaCochrane Database of Systematic Reviews • Authors' conclusions: Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

48. Future developments: • Disease modifying drugs: • 2 proteases beta and gamma- secretase • cleave the APP into A-beta fragments which form amyloid plaques •  APP Beta secretase Gamma secretase Abeta • Beta secretase (BACE= beta site APP clearing enzyme) • Future development of BACE inhibitors? • Inhibitors of tangle formation?

49. Management of Dementia: Medication for BPSD • Antidepressants • Antipsychotics • Anxiolytics • Hypnotics

50. Defensible prescribing of antipsychotics in Dementia • Consider non-pharmacological alternatives • Address vascular risk factors • Consent / capacity / best interests • Discuss risks & benefits with patients or carers • Identify target symptoms (psychosis, hostility, aggression) • Choose effective drug & dose • Choose time-frame during which to assess benefits (discontinue if no evidence or if harm) • If good response review need & aim to withdraw in c 3/12 if possible