Malattia di Alzheimer: L importanza della Diagnosi e del Trattamento Precoce: la Collaborazione MMG-Specialista

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1 55 Congresso Nazionale SIG Firenze Auditorium Palazzo dei Congressi 2 Dicembre 2010 Invecchiamento e Longevità: più Geni o più Ambiente Malattia di Alzheimer: L importanza della Diagnosi e del Trattamento Precoce: la Collaborazione MMG-Specialista Giancarlo Logroscino MD, PhD Dipartimento di Scienze Neurologiche e Psichiatriche Facoltà di Medicina e Chirurgia Università di Bari

2 The Clinical Problem Mayeux R. NEJM 2010; 362: A 72-year-old man who is still managing investments at a brokerage firm seeks consultation at the urging of his wife for increasing difficulty with memory over the past 2 years. Clients have expressed concern about his occasional lapses in memory. His wife reports that he frequently repeats questions about social appointments and becomes angry when she points this out. The physical examination is normal, but the patient has difficulty remembering elements of a brief story and adding a small amount of change. MMSE: 28/ 30

3 Dementia Diagnosis: A Three-Step Process 1. Identification of a Dementia Syndrome 2. Exclusion of Other Etiologies 3. Classification

4 Sequence of Pathological, Clinical, and Radiologic Changes from Normal Aging to Early AD Mayeux R. NEJM 2010; 362:

5 Classically only half of patients with chronic disease are identified, only half of those identified receive treatment, and only half of those treated are adequately, meaning that seven eigths are not being optimally managed. Editor Note BMJ April 24; 318(7191).

6 UK: Report by the Controller and Auditor General-2007 https// official-documents.gov.uk/hc0607.pdf Only 49% diagnosed Mostly in advanced stage of disease NO YES

7 Time To AD Diagnoses in Europe House of Commons:Improving Support and Services httpp// // months

8 Primary Care And Dementia Early diagnosis Best Management

9 The Health Improvement Network (THIN) UK 5 million patients in primary care Age,sex medical diagnosis, symptoms, health promotion activities, referral to secondary care, prescriptions, Townsend deprivation score Risk factors Recognition of a problem with diagnosis Entry of diagnosis in medical records 358 Practices Rait G et al BMJ ;341:c3584

10 Diagnosis of Dementia in UK GP Practices Rait G et al BMJ ;341:c3584 AD VAD Non Specific Dementia 82.2 years 68% Female

11 Survival of People with Dementia in Primary Care Rait G et al BMJ ;341:c ys 1.9 ys

12 Incidence of Dementia by Age and Sex ( ) Rait G et al BMJ ;341:c3584 Incidence= 3-4/1000 persons-year at risk

13 Incidence across 3 Studies: GP do not diagnose Dementia Rait G et al BMJ ;341:c3584

14 Dementia is underdiagnosed in Primary Care 1. Lack of simple test 2. Difficulties in disclosing the diagnosis 3. No training 4. Lack of time 5. No knowledge of available service

15 General Practitioner View on the Early Diagnosis Renshaw J et al BR J Gen Pract 2001: 51: GP: 55% response Early diagnosis useful only for 51% dementia is untreatable so why diagnose? early diagnosis will lead to wasteful plans and miseries.

16 GPs attitudes and practice: early diagnosis of dementia Ahmad S. Et al British Journal of General Practice,

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18 What Situations need Attention in Primary Care? Patients who spontaneously consult for a memory complaint The patients who is brought by his family who finds that they are not like they used to be ( behavioral change or functional decline) Patients with psychomotor slowing Emergency call for an elderly who is agitated, delirious, or confused

19 the German Study on Aging Cognition and Dementia in Primary Care Patients Bonn, Düsseldorf, Hamburg, Leipzig, Mannheim, and Munich medical record registry of general practitioners (GPs). Inclusion criteria age 75 years or older, absence of dementia according to judgment of GP at least 1 contact with the GP within the last 12 months

20 Assessment Structured interview for the diagnosis of Dementia Neuropsycho assessment Memory Orientation Language, perception, praxis Reasoning and problem solving ADL Geriatric Depression Scale

21 Do you Feel Like your Memory is Becoming Worse? No Yes, but this does not worry me Yes, this worries me

22 Baseline of 2075 Subjects in 4 Temporal Sequences Jessen, F. et al. Arch Gen Psychiatry 2010;67:

23 Subjective Memory Impairment with or without Worry at baseline: Conversion to AD Jessen, F. et al. Arch Gen Psychiatry 2010;67:

24 Second Analysis Among 2075 Subjects

25 Conclusions SMI is associated with the onset of dementia The risk is doubled in dementia with worry The risk is increased for AD but not for vascular dementia SMI with impairment were excluded from this study The risk is high in subjects with MCI at followup SMI is a pre MCI condition

26 What Situations need Attention in Primary Care? Patients who spontaneously consult for a memory complaint The patients who is brought by his family who finds that they are not like they used to be ( behavioral change or functional decline) Patients with psychomotor slowing Emergency call for an elderly who is agitated, delirious, or confused

27 Evolution of Instrumental Activities of Daily Living (IADL) before the AD diagnosis: 14 years Amieva H et al Ann Neurol 2008;64: years

28 What Situations need Attention in Primary Care? Patients who spontaneously consult for a memory complaint The patients who is brought by his family who finds that they are not like they used to be ( behavioral change or functional decline) Patients with psychomotor slowing Emergency call for an elderly who is agitated, delirious, or confused

29 Monzino 80+ Study prospective door-to-door populationbased survey among all eighty years or older residents eight municipalities in the province of Varese, Italy. Diagnosis of dementia was based on DSM-IV criteria. BDs presence in the month preceding the interview was assessed using the Spontaneous Behavior Interview-BD

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32 What Situations need Attention in Primary Care? Patients who spontaneously consult for a memory complaint The patients who is brought by his family who finds that they are not like they used to be ( behavioral change or functional decline) Patients with psychomotor slowing Emergency call for an elderly who is agitated, delirious, or confused

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34 Role of GP in the Diagnosis Villars et al NutritionHealth aging Early clinical diagnosis of typical cases 2. Lab and Imaging exams 3. Referral to specialty clinic

35 Early Referral to Tertiary Care Villars et al NutritionHealth aging 2010 Young patients Focal neurological signs Rapid progression Major BPSD Atypical clinical picture

36 The course of cognitive decline during disease-modifying or symptomatic treatment Hampel H et al. Nature Reviews Drug Discovery 9,

37 Two Approaches of Therapy with Cholinesterase-Inhibitors Smart G et al Alzheimer s & Dementia -(2010) 1 8 Rescue Early High Dose

38 AD Follow-Up: 1 or 3 or 6 Months? Villars et al NutritionHealth aging 2010 Prevention and treatment of complications Falls Malnutrition BPSD Admissions Hospital Nursing home

39 Dementia: Course and Preventive Strategies Intervention Primary Intervention Secondary Intervention Treatment Clinical State Normal Aging Subjective Memory Compalints Mild Cognitive Impairment Dementia Brain Pathologic State No Disease Early Brain Changes AD Brain Changes Disease Progression

40 PAQUID 3,777 individuals aged 65 years or older From different areas of Southwestern France University of Bordeaux

41 Assessing Cognition, Mood, Performances over Time Amieva H et al Ann Neurol 2008;64: MMSE: test of global cognitive performance Isaacs set Test semantic verbal fluency Generating words across semantic categories in 15 sec Wechsler Similarities Tests: Conceptual knowledge What way two things are alike Cognitive complaints Requiring subjects to trate their own perception of Word finding/ forgetfulness in daily living/difficulties in learning new info: Instrumental Activities of Daily living (IADL) Telephone use, transportation, finances, medication

42 Evolution of NP Test before the AD diagnosis: 14 years Amieva H et al Ann Neurol 2008;64: years Isaacs Set Test (IST) 10 years Wechsler Similarities 8 years MMSE 8 years Benton Visual Retention Test

43 Evolution of Depression (CES-D) before the AD diagnosis: 14 years Amieva H et al Ann Neurol 2008;64: years

44 Evolution of Memory Complaints before the AD diagnosis: 14 years Amieva H et al Ann Neurol 2008;64: years

45 the insidious accumulation of neurofibrillary pathology in the temporal areas, occurring about 12 years before the exteriorization of clinically defined AD

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47 Biomarkers in clinical research and development Hampel H et al. Nature Reviews Drug Discovery 9,

48 Individuals and Populations

49 Active Role of GP in Early Diagnosis Villars et al NutritionHealth aging 2010 Anmnestic interview Search for Episodic Memory Impairment Clinical Examination First Investigations Referral to Dementia Specialist

50 Short-term memory

51 Biomarkers in Clinical decision-making Hampel H et al. Nature Reviews Drug Discovery 9,

52 Time is Brain