an approach to a case of dementia by dr. subeg singh

1. AN APPROACH TO A CASE OF DEMENTIA
Moderater :-Dr.Arun Joshi (MD) Prof Head of Deptt
General Medicine
Presented By:-Dr.Subeg singh (PGJr2)General Medicine

2. DEMENTIA
• Cognitive function declines with aging
• • Age-related decline - cognitive speed, and working memory
• • General knowledge and vocabulary - stable or improve while
problem solving and reasoning decline

3. DEMENTIA
• DEMENTIA- the disease with acquired deterioration in cognitive/
intellectual abilities without impairment of consciousness.
• Cognitive deficit represent a decline from previous level of
functioning

4. • Dementia-characterised by multiple cognitive deficits of sufficient
severity to interfere with function during daily activities.
• DSM V criteria describe cognitive impairment and dementia in
neurocognitive disorders.
• An essential part of assessment is exclusion of depression or
delirium.

5. DSM-V
• • DSM-V -updated the prior criteria for dementia
• • “mild neurocognitive disorder”= MCI
• • “major neurocognitive disorder”=dementia

6. DSM CRITERIA FOR DEMENTIA
• 1. Memory impairment
• 2. At least one of the following:
• Aphasia
• Apraxia
• Agnosia
• Disturbance in executive functioning
• 3. Disturbance in 1 and 2 interferes with daily function
• 4. Does not occur exclusively during delirium

7. • • Alzheimer's disease is most
common dementia 50-75%
• • Dementia with Lewy bodies
15 to 35 %
• • Vascular dementia 5 – 20 %
• EPIDEMIOLOGY
• ~ 5 to 8 % at age 65 to 70
• ~ 15 to 20 % at age 75 to 80
• up to 40 to 50 % over age 85

9. CORTICAL VS. SUBCORTICAL DEMENTIA
• Subcortical
• Symptoms: behavioral changes, impaired affect and mood, motor
slowing, executive dysfunction, less severe changes in memory, extra
pyramidal findings.
• Affected brain regions: thalamus, striatum, midbrain, striatofrontal
projections.
• Examples: Parkinson’s disease, progressive supranuclear palsy, normal
pressure hydrocephalus, Huntington’s disease, Creutzfeldt-Jakob
disease, chronic meningitis.

10. REVERSIBLE CAUSES DEMENTIA
• D = Delirium
• E = Emotions (depression)& Endocrine Disease
• M= Metabolic Disturbances
• E = Eye & Ear Impairments
• N = Nutritional Disorders
• T = Tumors, Toxicity, Trauma to Head
• I = Infectious Disorders
• A= Alcohol, Arteriosclerosis

11. IRREVERSIBLE DEMENTIA
• Alzheimer’s
• Lewy Body Dementia
• Pick’s Disease (Frontotemperal Dementia)
• Parkinson’s
• Vascular
• Huntington’s Disease
• Jacob-Cruzefeldt Disease

12. Mild Cognitive Impairment (MCI)
• MCI - an in-between state of normal aging and dementia.
• • In MCI, cognitive change is greater than expected for age
• • Independence & ADL are preserved

15. MCI
MILD COGNITIVE IMPAIRMENT
• Subtyping MCI into amnestic and nonamnestic categories has
predictive value.
• • The vast majority of aMCI -AD dementia
• • naMCI –DLB, FTD, vascular dementia, and even Alzheimer dementia

16. MCI
• Annual risk in the elderly
• Gen. -1%–2%
• MCI(clinic setting) - 10%–15%
• In population-based studies - 5%–10%
• • A diagnosis of MCI even with reversion to normal has prognostic
value MCI

17. Preclinical Stage of Dementia
• Pathophysiological processes can begin decades prior to cognitive
symptoms.
• An evolving understanding of the preclinical stages possible
therapeutic time window.
• e.g. CSF Aβ 42 decreases ≈ 25 years before expected symptom onset
in AD.
• Preclinical stages of FTD have not been studied as much as AD.

18. Biomarkers predicting the risk of conversion Of
MCI to dementia
• MRI-MCI with hippocampal volumes -25th percentile – 2 to 3 times
risk compared 75th percentile.
• CSF-↓ Aβ 42 and ↑ t-tau and p-tau.
• APOE4 allele.
• Temporal-parietal hypometabolism on FDG-PET.
• Amyloid deposition on Aβ PET imaging .

19. DEMENTIA
• • 35.6 million worldwide in 2010- number would double
approximately every 20 years (Prince et al., 2013).
• • Rotterdam study,UK, Rochester- indicate the incidence of dementia
may be declining.
• • One possible explanation -improved treatment of vascular risk
factors.

20. I.Syndrome of progressive dementia(other
neurologic signs absent or inconspicuous)
• Alzheimer disease
• Some cases of Lewy-body disease
• Frontotemporal dementias-Pick disease, includin behavioral variant,
primary progressive aphasias (several types)

21. II. Syndrome of progressive dementia (in
combination with other neurologic abnormalities)
• Huntington disease (chorea)
• Lewy-body disease (parkinsonian features)
• Corticobasal ganglionic degeneration (rigidity, dystonia)
• Dementia-Parkinson-amyotrophic lateral sclerosis complex
• Cerebrocerebellar degeneration
• Familial dementia with spastic paraparesis, amyotrophy, or
myoclonus
• Polyglucosan body disease (neuropathy)
• Frontotemporal dementia with parkinsonism or ALS

22. TYPES OF DEMENTIA
• Cortical Dementia
• Subcortical Dementia
• Progressive Dementia
• Primary Dementia
• Secondary Dementia
• 1)damage to the brain that affects the cortex of the the brain or the outer layer (causes problems
with memory, language, thinking, and social behavior
• 2)dementia that affects parts of the brain below the cortex (causes changes in emotion, and
movement)
• 3)Dementia that only gets worse and starts to affect ones ability to do everything activities
• 4)dementia like Alzheimer’s disease and doesn’t result from any other disease
• 5)dementia that is caused from physical disease or injury (can affect people with other disorders
that affect mobility and functions like parksins

23. HOW TO DIAGNOSE A CASE OF DEMENTIA
• Clinical history
• Symptoms analysis
• Focussed physical examination
• Cognitive and neuropsychiatric examination
• Laboratory evaluation

24. CLINICAL SYMPTOMS
• COGNITIVE IMPAIRMENT
• FUNCTIONAL IMPAIRMENT
• NEURO-PSYCHIATRIC MANIFESTATIONS
• BEHAVIOURAL DISTURBANCES
• MOOD CHANGES
• ANXIETY
• PERSONALITY CHANGES
• PSYCHOSIS
• SLEEP DISTURBANCES

25. FOCUSED HISTORY
• Chronology of the problem- from loved ones
• - mode of onset – abrupt vs gradual
• - progression - stepwise vs continous decline
• - duration of symptoms
• Medical history
• Family history
• Socio-economic history
• Evaluation for toxic agent exposure

26. PHYSICAL EXAMINATION
• Neurological examination
• Mobility and balance assessment
• Focal neurological deficits
• Extra-pyramidal signs
• Vision & hearing screening
• Cardiac and pulmonary evaluation

27. COGNITIVE & NEUROPSYCHIATRIC EXAMINATION

28. INVESTIGATIONS

29. • DIFFERENTIAL DIAGNOSIS
• DELIRIUM
• MILD COGNITIVE IMPAIRMENT (MCI)
• AGE-RELATED COGNITIVE DECLINE
• MENTAL RETARDATION
• SCHIZOPHRENIA
• DEPRESSION
• FACTITIOUS D/A
• ALCOHOL ABUSE

30. DIAGNOSTIC APPROACH

31. ALZHEIMERS DISEASE
• ALZHEIMER’S DISEASE (AD)
• About 70% of all cases of dementia in elderly
• Incidence increases with age
• Occurs in up to 30% of persons >85 years old
• Characterized by:
• Progressive loss of cortical neurons
• Formation of amyloid plaques (beta-amyloid is major component)
and intraneuronal neurofibrillary tangles (hyperphosphorylated tau
proteins is major constituent)

32. • DIAGNOSTIC CRITERIA FOR DEMENTIA OF THE ALZHEIMER TYPE (DSM-IV)
• A. Development of multiple cognitive deficits
• 1. Memory impairment
• 2.other cognitive impairment
• B. These impairments cause dysfunction in In social or occupational
activities
• C. Course shows gradual onset and decline
• D. Deficits are not due to:
• 1. Other cns conditions
• 2. Substance induced conditions
• E. Do not occur exclusively during delirium
• F. Are not due to other psychiatric disorder

33. Alzheimer Pathophysiology
• Aβ is derived from APP through proteolytic processing
• Removed efficiently by a number of mechanisms
• Drained through the cerebral vasculature and into the CSF via the
glymphatic system.

34. CLINICAL MANIFESTATION
• Begin with memory impairment - language, visuospatial skills
• Anosognosia- unaware of difficulties
• Cognitive decline-driving,shopping,house-keeping
• Language impaired- naming,comprehension then - fluency
• Apraxia- seq. motor task can’t perform
• Visuo spatial deficits
• Delusions ,capgras syndrome – late stages
• End stage-rigid,mute ,incontinent & bed-ridden

35. • Neurological exam & neuropsychological testing
• Brain imaging: brain atrophy due to extensive neuronal loss and
hippocampal atrophy.
• Diagnosis confirmed by histology of post-mortem brain.
• ‘Plaques’ & ‘tangles’ in hippocampus & cerebral cortex.

36. Biomarkers in AD- CSF Biomarkers
• ↓ CSF Aβ 42 and ↑ CSF tau protein - sensitivity of 85% and
specificity of 86% for AD.
• These biomarkers can improve diagnosis in and predict conversion
from MCI to AD.
• Data on the progression from normal or preclinical AD are
accumulating but are not ready for clinical use at this time.

38. Neuroimaging Biomarkers
• MRI –very useful in the differential diagnosis of dementia and as a
biomarker in AD dementia.
•
• Medial temporal lobe atrophy of the hippocampus and entorhinal
cortex with dilatation of the temporal horns.
• Reduction in hippocampal volumes correlates with NFT pathology at
autopsy and cognitive decline

39. • Medial temporal lobe atrophic in early AD and later in the disease
atrophy rates are greater in the temporal, parietal and frontal
cortices.
• White matter hyperintensities (FLAIR or T2 MRI) also appears to
contribute to cognitive impairment in AD.

40. Cerebral Amyloid Angiography
• Hypointense signal on MRI GRE - hemosiderin deposition -
microhemorrhages.
• In the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Aβ load as
measured by PiB-PET
• CAA preferentially involves the occipital lobe.

41. Tau Imaging
• Tau comprises the other hallmark of the AD pathological process,
neurofibrillary tangles
• The ability to image it in vivo would be extremely useful.
• Also implicated in a variety of other disorders
• Specificity for tau and various tau isoforms??

42. Treatment-non pharmacological
• Avoiding prior triggers
• Limiting changes to the environment
• Regular exercise, and shifting attention.
• Aromatherapy
• Music therapy-reduces agitation

43. Passive immunization
• Bapineuzumab- first humanized monoclonal antibody
• Solanezumab- specific to (Ab16–24)
• Gantenerumab- specifically bind to aggregated Ab
• Crenezumab - a novel human IgG4 monoclonal antibody
• Reduced pro-inflammatory activity –low risk of vaso.edema.
• Currently, a phase II trial of crenezumab (NCT01343966) is ongoing in
patients with mild to moderate AD

44. TREATMENT
• Acetylcholinesterase Inhibitors
• N-Methyl-D-aspartate Receptor Antagonist
• Vitamin E- large double-blind RCT -mild to moderate AD-less decline
and delay in progression of about 19% per year without an increase in
mortality with high-dose vitamin E

45. VASCULAR DEMENTIA
• Refers to cognitive decline caused by ischemic, hemorrhagic, or
oligemic injury to the brain as a consequence of cerebrovascular or
cardiovascular disease.
• Part of a spectrum of vascular disease causing cognitive impairment,
which also includes mild cognitive impairment of vascular origin &
mixed Alzheimer's disease plus cerebrovascular disease.

46. CLINICAL CRITERIA FOR VASCULAR DEMENTIA

47. • Multi-infarct dementia
• - recurrent strokes
• - step wise progression
• - HTN,DM,CAD MRI
• - multiple areas of infarction
• Binswanger’s d/s
• Diffuse white matter disease
• lacunar infarction
• C/F:confusion,personality changes,psychosis pyramidal signs & cerebellar signs + .
• gait disorder,urinary incontinence,dysarthria emotional liability.

49. FRONTO TEMPORAL DEMENTIAS
• Often begins with marked behavioral disturbances, unlike AD
• Classic form – Pick’s disease
• Patients frequently hot-tempered and socially disinhibited
• memory & visuo spatial skills spared
• Impaired planning,judgement and language
• Echolalia +
• Overlap with PSP,CBD, motor neuron disease
• Illness progresses for years, like AD
• Inevitable decline
• MRI- lobar atrophy of frontal and/or temporal
• About 50% of patients have family history

51. DIFFUSE LEWY BODY DISEASE
• Patients have clinical parkinsonism with early and prominent
dementia.
• Lewy bodies found in brain stem, limbic system, and cortex.
• Visual hallucinations and cognitive fluctuations common, capgras
syndrome & REM sleep disorder.
• Longstanding PD without cognitive decline develop dementia.
• Better memory but severe visuospatial deficit.
• Patients sensitive to adverse effects of neuroleptics.
• May be second most common cause of dementia after AD.

53. PARKINSON’S DISEASE
• About 50% of patients have dementia by 85 years old.
• Affects executive function disproportionately.
• Dementia occur in later stage, or as a result of co morbidities-AD,DLB
or side effects of drug.
• Associated depression & anxiety.
• Frontal lobe dysfnct- complex tasks,planning, -memorizing.
• Language & mathematical skills spared.
• Predictors- late onset,akinetic-rigid,severe depression - advanced
stage

54. • CRUETZFELDT-JAKOB SYNDROME(CJD)
• Rapid progressive dementing prion disorder.
• Focal cortical signs, rigidity.
• Onset between 40- 75 years.
• 90% has MYOCLONUS vs 10% in AD.
• Progressive dementia and personality changes over weeks to months
Death <1 year from first symptom.
• EEG- diffuse slowing and periodic sharp waves or spikes.
• MRI- basal gangla abnormalities.
• CSF- detect specific aminoacid sequence (PrPSc)

55. DISORDERS OF MEMORY FUNCTION
(AMNESTIC DISORDERS)
• Aging-
• Mild loss of memory: names and dates.
• Most sensitive indicator of cognitive change: poor performance on
delayed-recall tasks.
• Verbal fluency remain intact and vocabulary may increase

56. Transient global amnesia-
• Dramatic memory disturbance.
• Affects patients >50 years.
• Usually have only one episode, lasting 6 to 12 hrs.
• Complete temporal and spatial disorientation.
• Orientation for person preserved.
• May be confused with psychogenic amnesia, fugue state, or partial
complex status epilepticus.
• May be due to vascular insufficiency to hippocampus or midline
thalamic projections

57. • Head injury
• Retrograde amnesia > antegrade amnesia.
• With time, memories usually return but rarely to recall events surrounding
trauma.
• Korsakoff’s syndrome
• Near-total inability to establish new memory.
• Patients confabulate about recent events.
• Immediate memory N,attention N.
• Most common cause: thiamine and other nutritional deficiencies with
chronic alcoholism

58. CLINICAL SUSPICIAN OF DEMENTIA
HISTORY &PHYSICAL EXAMINATION

59. REFERENCES
• Principles Of Neurology;Adams and Victor;10th edition.
• Harrison’s principles of Internal medicine 19th edition chapter no 448
,35 page no 170,2570.
• Davidson’s principles & practice of medicine 22ndchapter no 25 page
no 1432.
• API Text book of medicine 10th edition .
• Chamberlain’s symptoms & signs in clinical medicine 13th edition
•

60. THANK YOU