Dementia is a chronic progressive cognitive impairment affecting memory, intelligence and personality. It represents a decline from a previous level of functioning and does not refer to developmental conditions. Causes include Alzheimer's disease, vascular dementia, Lewy body dementia, and others. Alzheimer's disease is the most common cause and risk increases significantly after age 65. Pathology involves neurofibrillary tangles and amyloid plaques. Treatment focuses on managing symptoms and behaviors.

1. PRESENTER: DR.DEEPTI KAFLEY

2. WHAT IS DEMENTIA???
ACQUIRED,CHRONIC progressive cognitive impairment
(intelligence , memory and personality) in clear
consciousness
The cognitive deficits represent a decline from a previous
level of functioning,
does not refer to low intellectual functioning or mental
retardation , which are developmental and static conditions

3. CAUSES OF DEMENTIA :
REVERSIBLE
NONREVERSIBLE
DEMENTIA
VITAMIN DEFICIENCY
THYROID ABNORMALITY
VIRAL INFECTIONS
NORMALPRESS.HYDROCEPHALUS
TOXINS
ALZHIEMER’S DISEASE
VASCULAR DEMENTIA
LEWY BODY DEMENTIA
OTHERTYPES OF DEMENTIA

4. DEMENTIA
 Latin word …. Dementatus : “Out of one’s mind “
 Celsus (first century AD )……coin the term dementia
 Oribasius (fourth century ) …
wrote on cerebral atrophy loss of intellectual capacity and weakness of
movement
 Jean Dominique Esquirol

5. Described varieties of dementia
Also described about the clinical features
associated with dementia
Nineteenth century …separated cognitive
impairement caused from dementia to due
to mental illness
JEAN DOMINIQUE ESQUIROL

6. WILHELM GRIESINGER ( 1845)
First to describe about senile dementia as
a disease of cerebral arteries

7. ALOIS ALZHEIMER (1907)
 First to identify histopathological
changes associated with
progressive degenerative dementia
 Identified and described 2 cases of
dementia and characterized the
symptoms……
 Described neurofibrillary tangles
and plaques

9.  CAUSES LEADINGTO DEMENTIA

10.  Neurodegenerative :
Alzheimer's disease
Dementia with Lewy bodies
Frontotemporal dementia
Parkinson's disease /Huntington's disease /Vascular Infarction
Binswanger's disease
 Hemodynamic insufficiency
 Neurological disease :
Multiple sclerosis
Normal-p hydrocephalus
 Brain tumor (primary or metastatic)
Traumatic Subdural hematoma
Dementia pugilistica
 Exposure Alcohol Heavy metals, Irradiation
 Anticholinergic medications

11. Endocrine :
Hypothyroidism , Hypercalcemia, Hypoglycemia
Nutritional :
Vitamin B12 deficiency , Thiamine deficiency ,Niacin
deficiency
Metabolic Hepatic insufficiency
Renal insufficiency
Wilson's disease

12. Infectious
Human immunodeficiency disease
Creutzfeldt-Jakob disease
Gerstmann- Straüssler syndrome)
Neurosyphilis
Cryptococcus

13. ALZHEIMER’S DISEASE

14.  Epidemiology :
0.5% per year at the age : 65-69 years
1% per year from : 70-74 years
2% per year from age 75-79 years
3% per year from 80-84 years
8% per year from 85 years
About 13% of united states population over age 65 years affected
In 2007 ,> 5 million people affected
By 2030 , 7.7 million people

15. ALZHEIMER'S DISEASE IN NEPAL August 2016 For :
HelpAge International, Nepal Submitted by : Dr. Sharad
Koirala
 According to the Alzheimer's disease International (ADI),
there were about46.8 million people living with AD in the
world in 2015 which is estimated to double every 20 years
This will increase the population of the people with AD to
74.7 million in 2030 and 131.5 million in 2050
 The ADI , about 78,000 patients with AD in Nepal in 2015
and this number is bound to double every 20 years
reaching 134,000 in 2030 and 285,000 in 2050

16.  Genetics : Early onset / late onset
Three genetic loci
Amyloid precursor protein
Presenilin-1 ,chromosome 21
Presenillin-2 ,chromosome 1
Apolipoprotein –E
Familial /sporadic
Single gene: 2-4 fold
Allele,4 to 8 folds

17. ETIOPATHOGENESIS

18. Aggregation of insoluble
forms ,making fibrils
Current treatment
efforts in reduction
of AB production
Overproduction/inadequate
clearance
Synapse loss/neuronal death
Excitatory synapse
onto dendritic
spines are affected
Cleavage sites alpha,beta,gamma
Cleavage by alpha secretase -----------
soluble end products
Cleavage by Beta,Gamma secretase---
-----------amylodogenic

20. PATHOLOGY
 Atrophy confined to HIPPOCAMPUS
 Increased volume of inferior horn of lateral ventricle
 Widened sulci throught cortex
 Atrophy : posterior temporal , parietal , frontal lobes
 Neurofibrillary tangles : first found in Entorhinal cortex
…..hippocampus……lateral temporal lobe….neocortex…….

21. OTHER POSSIBLE ETIOLOGICALTHEORIES :
 Old age
 Low level of education
 Family history of dementia
 Decrease Estrogen Level : reduction after HRT
 History of head trauma
 Down syndrome ( by age 35 years)
 Myocardial ischemia in the elderly
 Exposure to Aluminum (Katzman and Kawas, 1994)

22. INVESTIGATIONS:
 Most promising approaches : AB In CSF
 CT SCAN/MRI : global and regional cortical regions need to be
seen
 SPECT………………………….PET have been used to examine
 Reduced blood flow with PITTSBURGH COMPOUND B
POTENTIATETO DEMONSTRATE BETWN.ALZHIEMER’S AND
COGNITIVE INTACT ELDERLY

23. VOLUME LOSS TEMPORAL AND PARIETAL AREA

24. VASCULAR DEMENTIA

25.  Second most frequent cause of dementia(25-50%)
Epidemiology :
 1.2 to 4.2% > 65 years
 6 to 12% > 70 years
 Is a syndrome
 Not a disease but a syndrome
 Complex interaction between vascular aetiologies , changes in
the brain , host factors

26. SUBTYPES :
 Acute onset
develops rapidly after succession of strokes
 Multi-infarcts
more gradual following a number of minor ischemic episodes
 Subcortical
history of hypertension +from clinical examination and
examination located in deep white matter
 Mixed cortical + subcortical
Mixed subcortical+ cortical components of vascular dementia may
be suspected from the clinical features

27.  Brain imaging findings :
No single pathological feature,ischaemic +infarcts+ischaemic white
matter lesions of varyeing size and type and atrophy of varyeing
degree and site
Deep infarcts in the Frontal ,Limbic ,Temporal, Parietal lesions
Single small lesion on imaging can be accepted as evidenced
MRI : focal brain infarcts (70-80%) cases
external white matter changes : 70-100% cases
PET scan : patchy reduction in blood flow

28.  Clinical features :
cognitive syndromes : memory deficit
slow information processing
mood/personality changes
Dysexecutive Syndrome
Behavioral/psychological symptoms : depression,anxiety
emotional lability
incontinence
Affected sites : Prefrontal cortex
Thalamus
Caudate , Pallidum

29.  Course and prognosis :
Relative abrupt onset
stepwise deterioration
fluctuating coarse of cognitive functions
Mean duration : 5 years
Survival is less than for general population or with
Alzhiemer’s disease

30. FRONTO-TEMPORAL DEMENTIA

31.  ARNOLD PICK…1892
First to describe about Pick
disease
was originally called "Pick's
disease"
Mainly involve the frontal and
the temporal lobe

32. Frontotemporal dementia : FLDTYPE
PICKTYPE clinical/pathol.
(LUND/MANCHESTER) MNDTYPE criteria
1994
NEARY ET AL (1998) : Progressive non-fluent aphasia
Semantic dementia
Corticobasal degeneration
Progressive supranuclear palsy

33. EPIDEMIOLOGY
 10.7 cases/ 100000 (50-60YEARS)
 28 cases / 100000 (60-70YEARS)
 PICKS DISEASE : 24 cases/ 100000
 FTD-MND : 2-6%

34.  CLINICAL FEATURES : modified Lund-Manchester
 Behavioral :
insidious , slow in progression
Early loss of insight , personal/ social awareness
Hyperoral state , impulsivity , distractibility
Disinhibition
 Affective symptoms : Depression , Anxiety,Apathy
 Speech disorders : decrease production(progressive)
perseveration , echolalia
 Early primitive reflexes
 Early incontinence ,rigidity , tremor

35.  Supportive diagnostic features :
< 65 years
positive family history
MND ( muscular weakness,wasting,fasciculation)

36.  ETIOLOGY :
SPORADIC / FAMILIAL (50% CASE,AUTOSOMAL DOMINANT)
GENE ASSOCIATED : Progranulin ( GRN) chromosome 17
Mutation in the Gene for MAPT

37. MRI SCANS
Fluorine-18-fluorodeoxyglucose positron
emission tomography (FDG-PET) scans
classically show frontal and/or anterior
temporal hypometabolism, which helps
differentiate the disease from Alzheimer's
disease
Cortical atrophy

38. FDG-PET DIFFERENCES

39. FRONTAL ANDTEMPORAL LOBEATROPHY END –STAGE
NO ATROPHY OFTHE PARIETALANDTHE OCCIPITAL REGION

40. LEWY BODY DEMENTIA

41.  Neurodegenarative dementia characterized by
progressive cognitive decline of sufficient
magnitude to interfere the daily activities
 15-25% of cases

42.  Clinical features :
Progressive cognitive decline (attention , visospatial
ability )
Recurrent visual hallucinations
Tremors ,frequent falls/faints
Syncope
Motor feautures of Parkinsonism (evidence of
dementia within 1 year of motor symptoms
differentiates it from LEWY BODY DEMENTIA)

44.  Neuropathology :Discovered in the early 1900s by Freiderich
H. Lewy
presence of Lewy bodies in the cerebral cortex
formation mainly by alpha synuclein , ubiquitin

45. What are LEWY BODIES ??????
Abnormal collections of (alpha- synuclein) protein within the
cytoplasm of neurons
Sites : Substantia nigra (parkinsonism)
Hippocampus (Alzheimer’s symptoms)
Neocortex ………but overall cortex can be affected

48. ALZHEIMER’S DISEASE LEWY BODY DEMENTIA
Early and prominent memory loss Only in advanced stage
Movement symptoms moderate/severe
stage
movement symptoms in early stages
Hallucination,delusion in later stages Hallucination,delusion in early stage
REM sleep disorder later stage
Autonomic disruption,B.P drop,falls
common
REM sleep disorder early
Autonomic disruption,B.P drop,falls
common

49. CREUTZFELDT-JAKOB DISEASE

50. • 1 case/million
• Causes : AD,mutation in PrP gene (chromosome 20)..aggregates
• Variant of CFJ : infected bovine meat (bovine-spongiform
encephalopathy …..MAD COW DISEASE
• Clinical features : personality changes
• Anxiety , depression, memory loss
• Difficulty swallowing
• Progress : myoclonic seizures
• Visual symptoms
• MRI : Hyperintensity over thalamus (POSTERIOR PART)

51. PULVINAR HYPERINTENSITY

52.  ALCOHOL INDUCED DEMENTIA

53. Severe memory loss
Confabulation
Apathy
Tremors
Hallucinations,delusions
Wernick’s Korsakoff syndrome
Malnutrition +brain damage
TREATMENT : vitamin
supplementation
Stop alcohol use

54.  TREATMENT OF DEMENTIA

55.  REVERSIBLE CAUSESTO BE RULED OUTAND
TREATMENTACCORDINGLY
 IRREVERSIBLE CAUSES
Cholinesterase inhibitor :
galantamine,tacrine,rivastigmine,donepezil
NMDA receptor antagonist : Memantine
Antipsychotics : quetipine,risperidone,olanzapine
Antidepressants : SSRI
Mood stabilizers : sodium valproate,carbamezepine

56.  Severe behavioral problems : haloperidol
 Supportive treatments :
family supports
physical exercises
nutritious food intake

57.  Recapitulating :

58. Memory loss(short term ) behavioral changes personality change
Dysphasia early primitive reflexes labile mood
Behavioral changes(wandering) early loss of insight insight present
Impaired smell sense early
Parkinsonism
Visual halluc.
Falls/faint
Reaction to antipsy
PRION
DISEASE HYDROCE.
Myoclonic Seizures
Cerebell. ataxia

60.  THANKYOU !!!!