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Differential diagnosis of dementia


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  • 1. Differential diagnosis of DementiaPROF.A.V.SRINIVASAN, MD, DM, Ph.D,DSc(HON), F.A.A.N, F.I.A. Emeritus Prof of Neurology and Former Professor of Neurology Head Institute of Neurology
  • 2. Senescence – a second childhood ! Whatever the Mind can conceive and Believe, the mind can Achieve Napoleon Hill
  • 3. Memory Memory holds together past and present , gives continuity and dignity to human life …. The companion…the tutor , the poet, the library with which you travel . Every discovery contains an irrational element or 4 creative intuition Khrl Popper
  • 4. Dementia – as a concept Mental disorder – accompaniment of senescence ? Alzheimer-1906- Amyloid plaques, neurofibrillary tangles Dementia : concept / a symptom/ a sign ,not a disease - decline in cognitive and intellectual functions compared to previous statusOne is the most independent, unconventional and individualistic of all numbers
  • 5. Case burden of DementiaIncidence: Vas et al . 2001 – 0.2& in males 0.3 & in females Chandra et al - 4.7 per 1000 person years in age 65 or above Reputation is made in a moment; character is built in a life time
  • 6. Reversible dementias Common causes; Alcohol, Medication related Metabolic – Hypothyroidism / parathyr. B 12 def. CNS infections – HIV , syphilis Surgical causes – NPH, chronic SDH tumour Improves with treatment Experience can be defined as yesterday’s answer to today’s problems
  • 7. Features suggesting reversibility Shorter duration of illness Subcortical type of dementia Moderately severe disturbance Younger age of onset Prominent gait disturbance Urinary dysfunction Focal neurological signs “Anger Begins In Folly And Ends In Repentance”
  • 8. Reversible dementias … Lab – CBC , PS,ESR, blood glucose LFT , RFT, Thyroid function tests Serum electrolytes incl. Calcium Serum B 12, VDRL, HIV Neuropsychological evaluation MRI ,CT CSF examination incl. VDRL EEGTwo is the most gentle of all numbers and represents, diplomacy and tact
  • 9. Conditions akin to dementia Depression - onset precisely dated , rapid progression , pervasive affective changes , unwilling to attempt cognitive testing No risk factors for dementia Can be a co-morbid condition “Social Isolation is in itself a pathogenic Factor for disease production”
  • 10. Akin To Dementia … Delirium – Acute onset – Fluctuating course – Autonomic disturbances – Precipitating factors like infection, metabolic and drugs The Truth is Fear & Immorality are two of the greatest inhibitors of Performance to progress
  • 11. Benign syndrome of MI Emil Kraeplin – OBS Consider when symptoms not progress Normal ageing >> Border zone << AD related to systemic neurological diseases, alcoholism, CCF, COPD Science is below the mind;
  • 12. AGE ASSOCIATED COGNITIVE DECLINE Decline of more than one SD in area of cognitive functioning in comparision with age matched controls When they tell you to grow up, they mean stop growing
  • 13. AssessmentNeuropychological instruments are useful in diagnosing and classifying the type of dementia Judging the severity of dementia following progress Assess efficacy of Rx In any field, find the strangest thing and explore it
  • 14. Assessment of dementia• Criterias used for identification• NINCDS-ADRDA ( AD)• VaD diagnostic criteria• FTD diag. criteria• DSM IV• Diagnosis of presence and extent assessed with MMSE , CDR Of a burning and unremitting character - F.W.PAVY
  • 15. Rx of dementia …• Treat potentially reversible primary and concomitant conditions• Multidisciplinary activity consists of neurologist, psychiatrist neurophysiologist and social worker• A concerned general practitioner knowing the patient & family Three is the most playful of all numbers and also creative, inspirational and motivating
  • 16. Dementia with lewy body Prominent attention deficit, fluctuating cognition, visual hallucins, parkinsonism Dopaminergic drugs useful Aypical antipsychotic drugs are used because marked sensitivity to neuroleptics Rivastigmine improves cognition and some behavioural disturbances Nine is the most humanitarian of all numbers. It is effort and sacrifice without the need for reward.
  • 17. Rx … ______________________________________________ Non-Pharmacological measures Minimise sensory deprivation Oral hygiene / Nutrition Maintain daily routines, reminders, diaries Flooring/clothing Foot-wears, walking aids NATURE, TIME AND PATIENCE are the 3 great physicians
  • 18. Care giver supports Acceptance , measures to counter physical, psychological, financial burden No denial or guilt Forming groups Education or providing recent treatment options Instituionalisation if necessary Number four is the most practical of all numbers, with attention and a sharp eye for details
  • 19. Rx - a team work Together Everyone Achives MoreIt is a great misfortune not to possess sufficient wit to speak well nor sufficient judgment to keep silent -La Broyers character
  • 20. Is there an answer for DementiaDiscipline Weighs ounces Regret weighs Tons
  • 21. General principles in Pharmacotherapy One agent at a time Increase dose at 5-7 days interval Sedative side effects used to advantage Improving cognition not the only goal Treat ass. behavioural disorders High CNS side effects can occur in very old patients Five is the most dynamic of all numbers. It is persuasive, versatile and adaptable
  • 22. Pharmacological Treatment of Dementia Cholinesterase inhibitors ( ChE-I) NMDA receptors antagonists Anti-oxidant drugs Anti-psychotic drugs “Men of Genius Admired: Men of Wealth envied women of power feared but only women of character are trusted” A- Friedman
  • 23. ChE-I Inhibits acetyl cholinesterase  Increases synaptic residue time of Ach. Increased signal in post synaptic cholinergic neuron Enhances cognition, improves behaviour, improves global function Knowledge without action is useless; Action without knowledge is foolish
  • 24. ChE-IBritish psychiatrists group recommend in probable AD in NINDS criteria, MMSE >10 (mild to moderate), duration > 6mthsLong term therapy found beneficialWhen the drug is withdrawn, worsening of ADL, behaviour needs restarting the drugs Number sixth is the most loving of all numbers and is harmonious with all other number
  • 25. AChEI -Dosages• Donapezil : Start on 5 mg OD, if tolerated increase to 10 mg OD , max. dose – 10 mg a day• Galantamine : Start on 4 mg BD and after 4 wks- 8mg BD may increase to max. dose 12 mg BD• Rivastigmine : Start on 1.5 mg BD –after 2 wks 3mg BD may increase to max. dose 6 mg BD Number seven is the most spiritual of all numbers. It is the seeker of truth.
  • 26. NMDA Receptor Antagonist Glutamine – learning , memory AD- increased glutamate activity at NMDA receptor  excitotoxic cell death Memantine – non competitive voltage dependant NMDA receptor antagonist low to moderate affinity Improves cognitive and global function We learn by thinking and the quality of the learning outcome is determined by the quality of our thoughts R.B. Schmeck
  • 27. MEMANTINE  Started in the dose of 5mg per day in first week and increased to 10mg per day  Memantine can be combined with ChE-I (Donapezil) for synergistic action  Antioxidant drugs like vitamin E Selegeline found to delay the occurance of milestones in the progression of dementiaEight is the most result-oriented of all numbers and represents a balanced world
  • 28. Other drugs Ginkgo biloba: Mixed results in trials. The effect is smaller than AChEI s Oestrogens: Not successful, risk of Venous thrombosis NSAIDs: Observations showed lower risk of AD with NSAIDs but clinical trials disproved efficacy The True Art of Memory is The Art of Attention - S.Johnson
  • 29. No time to lose Early diagnosis and intervention results in clinical and financial benefit by alleviating the patient and care giver burden Take time to think; it is the source of power Take time to read; it is the foundation of wisdom Take time to work; it is the price of success
  • 30. Vascular dementia Very common cause in India due to high prevalence of CVA/risk factors Unlike other dementias, disease modifying treatments (OHA, AHT, lipid lowering drug) can be beneficial Prevention of stroke and its recurrence is useful “By Nature All Men/ Women are alike but by Education widely different” - Chinese
  • 31. Two Diverging / Converging Pataways associated with VaDRisk factor CVD Ischemic Brain injury MRI lesion Clinical syndromeHTNArteriosclerosis 1. occlusion complete infarct lacune  lacunnar stateArteriosclerosis 2. Hypoperfusion incomplete infarct WHSM  Bingswanger syndrome Experience can be defined as yesterday’s answer to today’s problems
  • 32. Short comings1. Not interchangeable hence four fold rise in frequency2. DSM IV R most liberal3. NINDS- AIREN criteria conservative4. Gold standard for VaD (pathological definition difficult)5. Most of the criteria failed to distinguish between small and large vessel subtypes “Healthy Mind and Healthy expression of Emotion go hand in Hand”
  • 33. Diagnosis and prognosisRisk factors Modifiable Non-modifiable Hypertension Age Hyperglycemia Gender Race Heredity Discipline Weighs ounces Regret weighs Tons
  • 34. Diagnosis and prognosis contd….Vascular phenotype : “CVD” Arteriosclerosis Amyloid angiopathy Other small vessel disease “You have got to be before you can do and do before you can have”
  • 35. Diagnosis and prognosis contd…. Vascular Mechanism of Pathological distribution Brain injury phenotype “Infarct”Single artery Acute ischemia Multiple lacunarSmall arteriole infarctsSingle artery Acute ischemia Single strategically placed lacunar infarctBorder zone Chronic White matterSmall arteriole hypo perfusion demyelination and axonal loss
  • 36. Diagnosis and prognosis contd….neuro imaging phenotype CT lucency (lacunes and leukoariosis) MRI hyper intensity (lacunes and WMSH) A true commitment is a heart felt promise to yourself from which you will not back down - D. Mcnally
  • 37. Diagnosis and prognosis contd….Localisation / Clinical phenotype orneural network syndromeCortico-basal ganglia Lacunar state– thalamocortical Apathy, depression, abulialoops Dysexecutive syndrome Normal visual fields ParkinsonismCortico-basal ganglia Strategic infarct dementiathalamocortical loops Dysexecutive syndrome Frontal lobe syndromeDeep white matter Binswanger’s syndromeconnections Slowly progressive depression, bradykinesia, dysexecutive syndrome, gait apraxia, urinary incontinence
  • 38. Diagnosis of Dementia after strokeFour sets of criteria are used Sens Spec1. Hachinski ischemic score 89% 89% < 4 AD / 18, > 7 MID / 182. DSM IV 43% 95%3. NINDS – AIREN 50% 98%4. ADDTC criteria 50% 90% Every discovery contains an irrational element or 4 creative intuition - Khrl Popper
  • 39. AD Vs VaD AD VaDNeuro transmitter defect Hemodynamic defectFemale predominance Male predominanceGradual onset Abrupt onsetSteady deterioration Stepwise deterioration, fluctuating courseBP normal HypertensionNo history of stroke History of strokeGlobal decline in cognitive Focal neurological symptomsfunction and signsUnlikely to respond to May respond to a drug whichtreatment modifies microcirculation and enhance cerebral tissue perfusion A good teacher is a perpetual learner
  • 40. VaD  ChE-I especially Galantamine is found effective in VaD +/- AD  Pseudo bulbar palsy with emotional incontinene responds to SSRI , TCA or levadopa“Serious, sincere, systematic study surelysecures supreme success”
  • 41. Role of RIVASTIGMINE in VaDNo.of patients : 12Age group : 50 – 80 yearsFemale : 4Male : 8Most of them had diabetes and hypertensionNot based on subtype of VaD30% showed remarkable improvement in cognitive,curative and affective functions of the brainFuture study needed “ He who cannot forgive others destroys the bridge over which he himself must pass” - Annoy
  • 42. Strategies to prevent – STROKE – TO - DEMENTIA TEN-STEP APPROACH1. Treat hypertension optimally2. Treat diabetes3. Control hyperlipidaemia, use dietary control for diabetes, obesity and hyperlipidaemia4. Persuade patients to cease smoking and decrease alcohol intake5. Prescribe anticoagulants for atrial fibrillation6. Provide antiplatelet therapy for high risk patients A open foe may prove a curse ; but a pretended friend is worse
  • 43. Strategies to prevent – STROKE-TO-DEMENTIA contd…7. Perform carotid endarterectomy for severe (>70%) carotid stenosis8. Recommend lifestyle changes (e.g., weight loss, exercise, reduce stress, decrease salt intake)9. N-methyl-D-aspartate receptor antagonists, antioxidants)10. Intervene early for stroke and transient ischemic attacks with neuroprotective agents (e.g., propentofylline, calcium channel antagosists, -? Rivastigmine It is a great misfortune not to possess sufficient wit to speak well nor sufficient judgment to keep silent - La Broyers character
  • 44. FTLD Prominent aphasia and neuro-psychiatric complaints Familial, mutation in Ch. 17 SSRI decreases disinhibition, compulsion Adrenergic agonists ,Idazoxan improves planning ,attention & episodic memory “The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress”
  • 45. HIV associated Dementia Symptoms- Change in personality- mild to psychotic Loss of concentration, confusion Cognitive impairement Progressive subcortical dementia Signs –FND, seizures, meningeal signs, increased ICP signs “Healthy Mind and Healthy expression of Emotion go hand in Hand”
  • 46. Care and Cure !It is not your position that makes you happy or unhappyIt is your disposition
  • 47. Rx of Neuropsychiatric Problems An accurate diagnosis for both dementing illness and concomitant psychiatric symptoms Treatment of psychiatric problems reduce the distress of patient as well as caregiver As one is common to all numbers, it is often seen as the origin of all things
  • 48. Rx of Psychiatric sympt. Agitation – Mood stabilisers like CBZ, divalproax, Trazadone for night time aggression Buspirone for anxiety related aggression Medroxyprogesterone for sex aggression Anxiety - Oxazepam, Lorazepam, Buspirone Two symbolizes partnership implying that accomplishments are best through coordination.
  • 49. Rx … Apathy - Methylphenidate, dextro-amphetamine Modafenil Insomnia - Trazadone, Zolpidem Delusion- atypical antipychotics Depression – SSRI, Comb. RI eg. Venlafaxin,Mirtazepin Hate screeches, fear squeals; conceits trumpets but love sings lullabies
  • 50. Antipsychotic drugs when behavioural changes are severe and urgent treatment is needed, a Psychotropic drug can be used prior to use of a ChE-I drugThree can be seen in the divisions of a human in mind, body and spirit
  • 51. Therapy--? Future“Knowledge can be communicated but not Wisdom” - Hermann Hesse
  • 52. Future therapies Recently, intranasal insulin – improves cognitive function in AD who lack Apo E Gene therapy using nerve growth factor administered by implanting genetically engineered autologous fibroblasts “Motivation is the Spark that lights the Fire of Knowledge and fuels the engine of Accomplishment
  • 53. Future therapies• Regenerating neurons show trophic response  reduction in rate of cognitive decline by 50 % for about 2 years• Beta secretase inhibitors are found to interrupt amyloid cascade Learn to adapt, adjust and accommodate Learn to give, not to take and learn to serve not to rule
  • 54. Future Therapies• Drugs to counter Glycogen synthase kinase,which is involved in phosphorylation of tau,is under study• Plaque busters inserts themselves in polymerizing amyloid and so slows accumulation of Neuritic plaques In all of us, even in good men, there is a
  • 55. Dedicated to my family formaking everything worthwhile
  • 56. READ not to contradict or confuteNor to Believe and Take for Grantedbut TO WEIGH AND CONSIDER Thank you My sincere thanks toMr.K.THUDHIMUGAN for his meticulous computer work