Approach to dementia

Dementia is defined as an acquired deterioration in cognitive abilities that impairs the successful performance of activities of daily living (ADL).

1. Approach to Dementia Dr. Aminur Rahman FCPS (Med), MD( Neuro ) ,FINR (Switzerland), FACP (USA) Fellow Interventional Neuroradiology (Thailand) Assistant Professor Department of Neurology Sir Salimullah Medical College

2. Dementia Definition: Dementia is defined as an acquired deterioration in cognitive abilities that impairs the successful performance of activities of daily living (ADL).

3. Mild cognitive impairment (MCI) MCI  is a state intermediate between normal cognition and dementia, with essentially preserved functional abilities.

4. Domain of impairment Neuropsychological Behavioural Activities of daily living (ADL) Quality of life (QOL)

5. Neuropsychological problems- 80 % General intelligence (verbal & nonverbal) Memory (verbal and visual) Language Orientation Visuospatial perception Frontal lobe (executive) function

6. Behavioral disturbances Agitation Personality changes Abnormal eating behaviours Wandering Affective disorders/mood disorders Incontinence Anxiety, phobias, fears Delusions Restlessness Demanding/critical behaviour hallucinations Illusions Shouting/screaming Rage/violence Disinhibition Sleep-wake disturbances Sexual behabiours Compulsive/ritualistic behaviours

7. ADL Baseline self-care abilities Eating, drinking Toileting, washing Walking Dressing Complex everyday activities Shopping Food preparation House keeping Finances responsibilities

8. In Dementia, there is - Neuropsychological problems Behavioural disturbances Impaired ADL Leading to- Reduced QOL

9. Approach to Dementia Determine presence of Dementia -Decision is solely & essentially clinical Determine primary degenerative/other potential treatable causes of dementia Co-morbid medical illness. Treatment of an intervening illness may reverse a worsening of dementia Key points:

10. History of Present illness :Obtain a meticulous history (with temporal profile) Rate of intellectual decline Impairment of social function General health & relevant disorders-stroke, head injury History of past illness Nutritional status Drug history Personal history Family history of dementia Occupational history - toxins Approach to Dementia- History

11. History of present illness: Age - Younger: Secondary cases -Older: AD/other primary dementi a Sex: More women are affected by dementia than men. Worldwide, women with dementia outnumber men 2 to 1. Approach to Dementia - History (Contd.) Evaluation:

12. Approach to Dementia - History (Contd.) Meticulous history from - Patient -Independent informate -Spouse Patient difficulties: Difficulties patient having Family member notice

13. EN MID CZD NPH, AD Approach to Dementia - History (Contd.) 2. Time course & progression Weeks Months Years

14. Approach to Dementia - History (Contd.) Onset : i) Early onset e.g.. CADASIL Deficiency states Postencephalitic SSPE Wilson’s Disease Leukodystrophy ii) Late onset e.g.. Alzheimer’s disease (AD)

15. Approach to Dementia - History (Contd.) Duration : i) Long duration – AD ii) Short duration – Chronic subdural haematoma, Creutzfeldt-Jakob disease (CJD ) Temporal progression: i) Slowly progressive – AD ii) Relentlessly progressive – CJD, Huntington’s disease, other infections

16. 3. Function of the patient At work At home Performance of basic activities of daily life 4. Issue of safety Driving - accident, traffic violation, lost in driving Danger - to patient/others Approach to Dementia - History (Contd.)

17. 5. Etiologically directed history: Vascular disease-Risk factors Infections/toxic/metabolic/trauma Psychiatric-depression, insomnia, agitation Approach to Dementia - History (Contd.)

18. Approach to Dementia – History (Contd .) B. Past illness: Gastric surgery – vit . B12 deficiency Chancre – Neurosyphilis C. Nutritional status : Malnutrition has been associated with more severe symptoms of dementia D. Drugs – sedatives, tranquilizers E. Personal history: Alcohol – thiamine deficiency I.V. drug users – HIV infection

19. Approach to Dementia - History (Contd.) F. Occupational history: Working in chemical factory – lead, mercury etc. G. Family history : HD AD Frontotemporal Dementia (FTD) Wilson’s Disease CADASIL Some Hereditary Ataxias etc.

20. Problem with intellect- Memory impairment & judgment Abstract thinking Orientation problem- Time (Day) Place (Where) Person (Who ) Difficulties with language Change in personality Anxiety Agitation irritability Approach to Dementia – clinical features

21. Approach to Dementia – clinical features Poor memory : Persistent complaint(recent > remote ) Disturbed behaviour : Personality Mood PerceptioN Attention and Concentration C. As dementia worsens: Less able to self care Neglect social connection Disoriented Slowing of thought Behaviour aimless, stereotypic mannerism Persecutory delusion Mute

22. Table: Dementia associated prominent behavioral features Major Types Dementias Associated behavioral disturbances Alzheimer disease Depression, Irritability & Anxiety, Apathy, Delusions, Paranoia &Psychosis Lewy body dementia Fluctuating confusion, Hallucinations, Delusions, Depression & Rapid eye movement behavior disorder (RBD) Vascular dementia Depression, Apathy, Psychosis Frontotemporal dementia Early impaired judgment, Disinhibition, Apathy, Depression, Delusions & Psychosis. Parkinson’s disease Depression, Anxiety, Drug associated hallucinations and Psychosis & RBD. Corticobasal degeneration Depression, Irritability, RBD and Alien hand syndrome.

23. Neurological examination: Mental state: Difficulties in assessing in Lethargic Inattentive Aphasic Agitation: Evening disorientation & agitation is called Sun downing occurs in Primary Dementia a. Alertness/ attentiveness: Depends on education level Serial 7s Count back words Approach to Dementia – Physical Examination

24. b. Memory: Immediate recall Short term/long term memory c. Aphasia: Fluency -Non fluent speech -Loss of grammar/syntax -Word finding difficulties Naming - Anomia - Non specific Auditory comprehension of single & multi step commends -Single step: Show two fingers -Multi step: With your eyes closed tap your right knee with two fingers of your left hand Approach to Dementia – Examination

25. Repetition of unfamiliar phrases Reading aloud Writing -Name -Directed sentences -Spontaneous sentences Listen for paraphasic error -Phonemic: tadle for table -Semantic: door for window d. Calculations : Educational level -Two digit addition/multiplication Approach to Dementia – Examination Contd.

26. e. Hemineglect: Target cancellation - Circle all letters - Look for left right asymmetry - Bisect horizontal line f. Apraxia: Impairment of the execution of a learned/ imitated movement in absence of weakness/sensory loss/ Incoordination Opening a look with key Ideometer ideational g. Drawing Copy a complex figures Approach to Dementia – Examination Contd.

27. Approach to Dementia - examinations (contd.) So “ A thorough examination is essential ” is mandatory AD: Does not affect motor system untill late stage VaD : Hemiparesis, pseudobulbar palsy or other deficits. FTD: Axial rigidity, supranuclear gaze palsy Dementia with Lewy body (DLB): Parkinsonian features PSP: Unexplained falls, Axial rigidity CBD: Dystonia, asymmetric motor deficit, alien hand, myoclonus

28. Approach to Dementia - examinations ( contd.) B12 deficiency: Myelopathy, peripheral neuropathy Other vit . Deficiency and heavy metal poisoning: Peripheral neuropathy Hypothyroidism: Dry cool skin, hair loss, bradycardia HD: Chorea CRF: Anemia, HTN CLD: Features of portal hypertension, palmar erythema , gynaecomastia etc. Paraneoplastic eg Carcinoma bronchus – clubbing

29. Korsakoff’s syndrome: ophthalmoplegia, confabulation, Neurosyphilis: Argyll Robertson pupil HIV infection: Opportunistic infections, Kaposi's sarcoma Chronic lead poisoning: Blue lines in gums Arsenicosis: Mee’s lines Wilson’s disease: K. F. Ring Approach to Dementia - examinations (contd.)

30. Assessment Scales Mini mental scale (MMS) Clinical dementia rating ( CDR) Geriatric mental state ( GMS) Cambridge evaluation for mental disorders (CAMDEX) Community screening instrument for dementia (CISD)

31. Assessment Scales of Cognitive and Neuropsychiatric examinations Mini – Mental Status Examination (MMSE) is important for : Diagnosis Prognosis Treatment

32. Assessment Scales of Cognitive and Neuropsychiatric examinations (contd .) Mini – Mental Status Examination (MMSE): Points Orientation: Name – season/date/day/month/year – 5 (1 for each) Name – hospital/floor/town/state/country – ` 5 (do) Registration: Identify three objects by name and ask patient to repeat – 3 (do) Attention and calculation : Serial 7s, substract from 100 –------- 5 (do) Recall: Recall the three objects presented – 3 (do) Earlier

33. Assessment Scales of Cognitive and Neuropsychiatric examinations(contd .) Mini – Mental Status Examination (MMSE-contd.): Points Language : Name pencil and watch – 2 (1 for each) Repeat “no ifs, ands or buts – 1 Follow a 3 step command ( eg . Take this paper, fold it in half and place it on the table) – 3 (1 for each) Write “ close your eyes” and ask patient to obey written command – 1 Ask patient to write a sentence – 1 Ask patient to copy a design - 1 Total 30 Note: score 24 or below indicates cognitive impairment

34. Stages of the disease by MMS 27-30 = Normal 25-26 = Possible 10-24 = Mild-moderate 6-9 =Mod-severe <6 = Severe

35. Motor: a . Focal weakness/neurological sign: Structure brain disease - MID, SDH, ICSOL b. Adventitial movements : Tremor, chorea, myoclonus - degenerative dementia, sub cortical c. Co-ordination & gait: Slow settling- PD/PD plus Ataxia- Wernick-korsakoff NPH Approach to Dementia – Examination Contd.

36. d . Primitive reflexes / Frontal release signs: Palmar grasp : Baby naturally grabs objects placed in palm. Palmomental reflex: stroking on the thenar eminence of the hand causes contraction of sub mental muscles . Rooting reflex: Baby finds breast to suckle. Sucking reflex: Baby sucks breast / bottle / teat to get milk. Snout reflex: Involved in suckling. Glabellar reflex: May protect eyes in certain situations. Selected physical examination Secondary reversible cause Factors for deteriorating, Intercurrent infection, Electrolyte imbalance Approach to Dementia – Examination Contd.

37. Primitive reflexes / Frontal release signs

38. Primitive reflexes / Frontal release signs

39. Clinical differentiation of Major Dementias Disease Initial symptom Mental status Neuropsy-chiatry Neurology Imaging AD Memory loss Episodic memory loss Initially normal Initially normal Entorhinal & hippocam-pal atrophy Vascular (VaD) Often sudden, variable initial symptoms, focal lesions Frontal/exec- utive cognitive slowing, can spare memory Apathy, delusions, anxiety Usually motor slowing, spasticity, can be normal Cortical or subcortical infarctions etc. FTD Apathy, reduced judgment,/insight/speech/ language, hyperorality Frontal/ executive, language,spare drawing Apathy, euphoria, depression Vertical gaze palsy,axial rigidity, dystonia Frontal & or temporal lobe atrophy

40. Disease Initial symptom Mental status Neuropsyc-hiatry Neurol-ogy Imaging DLB Visual hallucination, REM sleep disorder, delirium,Parkins-onism, Capgras syndrome Frontal/ executive, spares memory Visual hallucinations, depression, delusions Parkins-onism Posterior parietal , hippocampus -- larger than in AD PRION Dementia, mood change, anxiety, movement disorder Variable, frontal/ex-ecutive, memory Depression, anxiety Myoclon-us, rigidity, Parkins-onism Cortical ribboning, basal ganglia hyperintensities on FLAIR MRI Clinical differentiation of Major Dementias( Contd.)

41. Investigations for Dementia Objectives: To arrive to a confirmed diagnosis in collaboration with history and clinical findings To find out the reversible types of Dementia.

42. Investigations for Dementia (contd.) Routine: Thyroid function test: eg . Hypothyroidism Serum Vit. B 12 Assay- Pernicious Anaemia Complete blood count (may give a clue): Vitamin deficiency states Organ failure Endocrinopathies neoplastic conditions Toxic causes. eg , Basophilic Stippling of RBC in lead poisoning Vacuolated lymphocytes in Niemann -Pick disease 4. Electrolytes: Eg . Increased K + in CRF, Addison’s Disease

43. Investigations in Dementia (contd.) A. Routine (contd.): 5. VDRL: Neurosyphilis, False positive in SLE 6. CT/MRI of brain (MRI preferable in most cases) Brain atrophy in different topography in different conditions Stroke, Binswanger’s disease CNS infections ICSOL Hydrocephalus Leukodystrophies Wilson’s Disease Hallervorden-Spatz Disease

44. Neuroimaging findings in different Dementia s

45. F ig: Vascular dementia- Infract Neuroimaging findings in different Dementias

46. F ig: FTD Neuroimaging findings in different Dementia s

47. F ig: DLB/ AD Neuroimaging findings in different Dementias

48. Investigations for Dementia (contd.) B. Optional Focused Tests: Chest Skiagram :- Cardiomegaly - Stroke, Hypothyroidism, Anaemia, Alcoholism, Etc. Ca- Bronchus Pulmonary Tuberculosis Vasculitis- SLE, Wegener’s Granulomatosis Sarcoidosis 2. CSF Study: CNS INFECTIONS. Eg . HIV, Neurosyphilis Decreased A ß 42 - Amyloid & increased tau protein in AD- Not diagnostic

49. Investigations for Dementia (contd.) B. Optional Focused Tests (contd.) : 3. Liver Function tests 4. Renal function tests 5. Urine toxin screen. Eg . Lead, Arsenic, Mercury 6. Apolipoprotein - E genotyping- in “AD ” 7. DNA testing for Presenilin -1 (ps-1)-in “AD”

50. Alzheimer's disease

51. Alzheimer's disease is the commonest form of dementia. In this brain, the gross appearance of the brain reveals marked atrophy. The brain weighs lighter and there is atrophy of the gyral convolutions with widening of the sulcal spaces. Alzheimer's disease

52. Alzheimer's disease

53. Alzheimer's disease

54. Alzheimer's disease

55. Neurofibrillary tangles are twisted, disfigured cytoplasmic filaments found in cortical neurons. They contains altered intermediate filaments. They can be demonstrated by special silver staining methods. Together with neuritic plaques, they constitute the histological substrates of Alzheimer's disease. Neurofibrillary tangles in Alzheimer's disease

56. Investigations for Dementia (contd.) B. Optional Focused Tests (contd.): 8. DNA repeat expansion (CAG) OF Gene encoding Huntingtin on chromosome-4 Diagnostic for HD . 9. Decreased transkeltolase activity in Korsakoff’s syndrome 10. Measurement of P r P sc in CJD------------ Diagnostic

57. Investigations in Dementia (contd.) C. Occasionally helpful: EEG:- Repetitive bursts of diffuse high voltage sharp waves in CJD Non-convulsive seizure Encephalopathies 2.Parathyroid function 3. Adrenocortical function 4 . ESR: Vasculitis, CNS infections, Malignancy

58. Investigations in Dementia (contd.) C . Occasionally helpful (contd.): 5. Angiogram: Specially isolated CNS vasculitis 6. Brain & Meningeal biopsy: Not routine Isolated CNS vasculitis Potentially treatable neoplasm Young persons where diagnosis is uncertain 7.SPECT: Not routine In atypical “AD”- Hypometabolism & hypoperfusion in posterior temporo -parietal cortex 8.PET:- Almost exclusively a research tool

59. Conclusion Proper diagnosis of Dementia is essential for therapeutic & prognostic purposes. Thorough history & clinical examination are indispensable. In many situations, these two can produce the confirmed diagnosis even without laboratory investigations. A patient of Alzheimer’s disease may have stroke without Dementia & vice- versa. In many situations, laboratory investigations are adjunctive, not diagnostic. In some situations, laboratory investigations are confirmatory. Eg . CNS infections, ICSOL, Wilson’s disease, toxic conditions, HD, etc.

60. Thank you