DEMENTIA; A COMPREHENSIVE APPROACH

1. TREATABLE DEMENTIA

2. DEMENTIA
Acquired deterioration in cognitive abilities that impair successful
performance of activities of daily living.
Cognitive impairment represents a decline from previous level of
functioning.
Episodic memory, the ability to recall events specific in time & place,
is the cognitive function most commonly lost.
Dementia may erode language, visuospatial, praxis, calculation,
judgement & problem solving abilities

3. Alzheimer's disease is most common cause of dementia (50-75%)
Vascular dementia is second most frequent cause

4. NEURODEGENERATIVE Alzheimer's Ds ; Parkinson’s Ds & Dementia with Lewy Bodies, Fronto-temporal
dementia
VASCULAR Multi-Infarct; Diffuse white matter diseases(Binswanger’s)
NEUROLOGICAL MS, Huntington’s ds, MSA, Hereditary ataxias, Prion Ds
(Creutzfeldt jakob & GSS), ALS-parkinsonism-dementia complex
of Guam, Adult Down’syndrome with Alzheimer ds, Brain tumour
ENDOCRINE Hypothyroidism; Cushing syndrome; Adrenal insufficiency; Hypo
and Hyperparathyroidism
NUTRITIONAL Def. of Vit.B12(SACD),Thiamine(Wernicke’s), Niacin(Pellagra)

5. INFECTIOUS HIV; Neurosyphilis; JC virus(PMLE), TB, Fungal, protozoal,
Whipple
METABOLIC Hepatic/ Renal Insufficiency; Wilson’s Ds
TRAUMATIC &
DIFFUSE BRAIN
DAMAGE
Chronic Subdural Haematoma; Dementia pugilistica(chronic
Traumatic encephalopathy),Postencephalitis, Postanoxia,NPH,
Intracranial hypotension
TOXIC AGENTS Alcoholism; Heavy Metals(Pb,Hg,As,Al)
Drug/medication
intoxication
(Sedatives, tranquilizers & analgesics)
PSYCHIATRIC Depression(Pseudodementia),Schizophrenia,Conversion
disorder
MISCELLANEOUS Sarcoidosis,Vasculitis,CADASIL,Acute intermittent porphyria

6. IRREVERSIBLE DEMENTIA
• Alzheimer’s
• Vascular
• Lewy Body Dementia
• Parkinson’s
• Frontotemperal Dementia
• Huntington’s Disease
• Cruzefeldt Jakob Disease
• Leukoencephalopathies

7. REVERSIBLE DEMENTIA
• D = Drugs
• E = Emotions (Depression) & Endocrine Disease
• M= Metabolic Disturbances
• E = Eye & Ear Impairments
• N = Nutritional Disorders, NPH
• T = Tumors, Toxicity, Trauma to Head(SDH)
• I = Infectious Disorders
• A = Alcohol, Arteriosclerosis

8. REVERSIBLE DEMENTIA
• One out of five cases of dementia may have a condition, which may
respond to definite treatment.
• In a study of 1000 persons attending a memory disorder clinic, 19%
had a potentially reversible cause of the cognitive impairment and
23% had a potentially reversible concomitant condition. The three
most common potentially reversible diagnoses in this series were
• Harrison principles of internal medicine
Depression Hydrocephalus
Alcohol
dependence

9. CAUSES OF REVERSIBLE DEMENTIA
• Alcoholism
• Drug/medication intoxication
• Vitamin deficiencies
• Endocrine disorders
• Organ failure
• Chronic infections
• Chronic subdural hematoma
• Normal-pressure hydrocephalus
• Neoplasm
• Psychiatric Disorders

10. • Sarcoidosis
• Vasculitis
• Acute intermittent porphyria

11. ALCOHOL-RELATED DEMENTIAS
Alcoholism can predispose to cognitive impairment by a variety of
mechanisms.
Major alcohol-related conditions include -
Alcoholic cognitive
impairment
(alcoholic dementia)
Wernicke-Korsakoffs
syndrome
Marchiafava-
Bignami disease

12. Alcoholic cognitive impairment (alcoholic
dementia)
• It is a term used to designate a presumably distinctive form of dementia that
is attributable to the chronic, direct effects of alcohol on the brain.
• “a gradual disintegration of personality structure, with emotional lability,
loss of control, and dementia"
• Light-to moderate alcohol consumption can lower the risk of dementia, heavy
alcohol consumption leads to brain injury.
• Heavy alcohol intake involves ten or more years of at least 150 mL or 120 g of
absolute alcohol per day.
• Alcoholic dementia -more apparent in elderly than in young and appears
earlier and with less alcohol consumption in women than in men.

13. Alcoholic cognitive impairment (alcoholic
dementia)
• mild and minimally progressive frontal-executive disorder
• Poor working memory
• Decreased verbal fluency
• Circumstantiality
• Perseveration
• Impaired abstraction
• Decreased behavioral initiation

14. Alcoholic cognitive impairment (alcoholic
dementia)
• DIAGNOSIS- MRI
• Ventricular enlargement
• Diffuse atrophy disproportionately affecting prefrontal regions.
• The apparent cortical atrophy is partially reversible with continued
abstinence, possibly by rehydration.
• Abstinence also results in a partial reversal of neuropsychological
deficits and white matter volume loss in the frontal lobes

15. The Wernicke-Korsakoff Syndrome
• Severe thiamine (vitamin B1) deficiency
• chronic alcoholics with poor nutritional intake
• abrupt onset of ophthalmoplegia, ataxia, and delirium (Wernicke’s
encephalopathy or WE) followed by a prolonged amnestic disorder
consisting of loss of memory and confabulatory loss (Korsakoff’s
syndrome)

16. • Korsakoff ’s syndrome has specific features.
• The amnesia has an anterograde component with inability to learn
new material and a retrograde component affecting the recall of
information learned for up to several years prior to onset of the
syndrome
• The recall of more remote information is less impaired than is
recently acquired knowledge.
• On neurologic examination, nystagmus, ataxia, and peripheral
neuropathy are common.

17. Diagnosis of WKS
• MRI changes in the WKS occur in the diencephalic region
• Shrinkage of the anterior diencephalon, atrophy of the mammillary
bodies, and enlargement of the third ventricle with areas of
hypodensity in its walls and around the sylvian aqueduct

18. Treatment
• Thiamine administration.
• Adequate nutritional supplementation and the thiamine enrichment
of flour or other foods can prevent its development.
• Once established, the memory deficit does not immediately reverse
with thiamine administration, but adequate thiamine should prevent
worsening or recurrence of the disorder. If thiamine intake is
subsequently maintained, some degree of spontaneous recovery
occurs in most Korsakoff ’s patients.

19. • If thiamine is administered in the acute stage of WE,ophthalmoplegia
may reverse within a few minutes or hours, and the other
abnormalities may improve gradually over the course of several days.

20. Marchiafava-Bignami Disease
• Hallmark - acute demyelination of the corpus callosum
• Middle-aged Italian males with excessive intake of red wine
• Rarely in non-alcoholics,females
• Disorder may start with stupor or coma
• ON RECOVERY
Seizures
Dementia with complex
attention deficits
Memory and language
difficulty
Inter-hemispheric
disconnection

21. Diagnosis of MBD
• MRI - Changes consistent with demyelination
• Moderate atrophy of posterior callosal regions and severe atrophy of
anterior callosal regions in the setting of generalized atrophy.
• On T1-weighted images, there are areas of diminished signal
intensity with gadolinium enhancement in the corpus callosum
• hyperintense lesions in the central portion of the corpus callosum
with sparing of upper and lower layers, subcortical white matter,
putamen on T2WI and FLAIR

22. MRI Brain (T2W Saggital Section) -
Hyperintense
Lesions in the Central Portion of the Corpus
Callosum.

23. Treatment
• High-dose vitamin B complex - 500 mg/day
• Thiamine administration daily intramuscularly for 14 days followed
by once weekly for one month

24. VITAMIN B12 DEFICIENCY
• The most common cause is autoimmune chronic atrophic gastritis with
decreased intrinsic factor necessary for B12 absorption (pernicious)
• features of B12-deficiency dementia are psychomotor slowness,confusion,
memory defects, depression, and psychosis.
• associated peripheral neuropathy with superficial sensory impairment,
burning paresthesias, and early loss of ankle jerks
• demyelinating myelopathy of the posterior and lateral columns (sub-acute
combined degeneration) with impaired vibratory sense, limb weakness,
spasticity, increased muscle stretch reflexes, and extensor plantar responses.

25. Diagnosis
• Low serum B12 levels (<200 pg/mL)
• Serum methylmalonic acid and homocysteine levels - rise as markers of
tissue B12 deficiency and decline in response to therapy.
• Antiparietal cell and-intrinsic factor antibodies as well as a positive Schilling
test.
• Megaloblastic anemia, oval macrocytosis, poikilocytosis, leucopenia with
hypersegmented polymorphonuclear leukocytes, and a thrombocytopenia
• The neurologic manifestations can occur in the absence of these hematologic
features

26. Treatment
• 1000 μg of vitamin B12 IM daily for 10 days, weekly for a month, and
monthly thereafter.
• Neurologic improvement is usually evident within a few days of
initiating therapy and is often complete by one month, but
permanent deficits may remain
• Folic acid administration may reverse the hematologic
abnormalities of B12 deficiency while allowing the neurologic
changes to progress

27. HYPOTHYROIDISM (MYXEDEMA)
• Psychomotor retardation
• apathy
• lethargy
• depression
• “myxedema madness” with deficits in attention and memory,
paranoia, and hallucinations
• Cranial nerve and peripheral neuropathies
• myopathy, ataxia, coma, and seizures

28. TREATMENT
• Hypothyroidism is treated by administering exogenous thyroid
preparations.

29. HYPERTHYROIDISM
• Most commonly in the second and third decades
• Women >men
Anxiety irritability
poor
attention
impaired
memory
Restlessness
difficulty with
calculations
emotional
lability
distractibility
DEMENTIA

30. TREATMENT
• Treat underlying cause of the thyrotoxicosis
• Some symptoms may be controlled by Propranolol therapy

31. HASHIMOTO’S ENCEPHALOPATHY
• Sub-acute dementia
• confusion
• frontotemporal deficits
• delusions
• myoclonus
• ataxia
• stroke-like episodes

32. Hashimoto’s encephalopathy typically affects patients when they are
euthyroid.

33. DIAGNOSIS AND TREATMENT
• Marked elevations in antibodies against thyroglobulin or thyroid
peroxidase.
• Anti-neuronal antibodies may be positive-suggesting a shared
antigen between the brain and the thyroid gland.
• Bilateral mesial temporal atrophy with increased signal on T2-
weighted MRI.
• Recovery is quick when treated with corticosteroids.

34. CUSHING’S DISEASE
• Long-term overproduction of glucocorticoids by the adrenal medulla
• Neurological manifestations include
• depression
• psychomotor retardation
• irritability
• poor concentration and memory
• psychosis
• disturbed sleep patterns.

35. DIAGNOSIS AND TREATMENT
• Elevated serumcortisol levels
• Increased urinary excretion of 17-hydroxycorticosteroids
• Failure to suppress serum cortisol levels following administration of
dexamethasone.
• Hippocampus and frontal lobe functions may be particularly
disrupted in Cushings disease.
• When serum cortisol levels return to normal, the mental status
alterations resolve

36. ORGAN FAILURE LEADING TO DEMENTIA
• Renal failure
• Liver failure
• Pulmonary failure

37. RENAL FAILURE-UREMIC ENCEPHALOPATHY AND
DIALYSIS DISEQUILIBRIUM SYNDROME
• Neurological manifestations include
• fluctuating level of consciousness
• disorientation
• impaired attention
• sleep inversion
• headache
• seizures
• Clinical signs- Asterixis and myoclonus
• Dialysis and Renal transplant.

38. • Uremic encephalopathy-accumulation of metabolites, hormonal
disturbances, changes in intermediary metabolism, and changes in
concentration of excitatory and inhibitory neurotransmitters-
neurological manifestations.
• Electrolyte disturbances- hypercalcemia, hypophosphatemia,
hyponatremia, and hypermagnesemia-results in cognitive dysfunction

39. DDS
• Dialysis disequilibrium syndrome -occurrence of neurological signs
and symptoms, attributed to cerebral edema, during or following
shortly after intermittent hemodialysis
• Associated with high solute removal such as urea during HD.
• Prevention is the mainstay of therapy-initial dialyses should be
gentle, but repeated frequently.
• The aim is a gradual reduction in blood urea nitrogen.

40. LIVER FAILURE-CHRONIC HEPATIC
ENCEPHALOPATHY
• Potentially reversible disturbance in CNS function secondary to
hepatic insufficiency or portal-systemic shunting.
• Neuropsychiatric symptoms-onset is insidious-starting with changes
of personality and alterations in sleep patterns,shortened attention
span and lack of muscular coordination including asterixis follow,
progressing eventually through lethargy to stupor and coma.
• Diagnosis - history and clinical examination.
• Elevated serum ammonia level in the appropriate clinical setting is
highly suggestive of the diagnosis.

41. • The MRI studies of the brain of
cirrhotic patients typically
display a characteristic pallidal
hyperintensity in T1-weighted
images

42. TREATMENT
• Management of precipitating factors
• Strategies to lower ammonia levels including administering certain
sugar molecules (e.g.,lactulose) or antibiotics to reduce the
production of ammonia in the gastrointestinal tract.

43. CHRONIC INFECTIONS CAUSING DEMENTIA
• Neurosyphilis
• Whipple’s disease

44. NEUROSYPHILIS
• Asymptomatic and symptomatic
• Asymptomatic-who lack neurologic symptoms and signs but who
have CSF abnormalities-mononuclear pleocytosis, increased protein
concentrations or reactivity in the CSF VDRL test
• Symptomatic-major clinical categories include meningeal,
meningovascular, and parenchymatous syphilis
• Parenchymatous syphilis includes general paresis and tabes dorsalis
• All these disease processes are different clinical expressions of the
same fundamental pathological events, especially meningeal
invasion, obliterative endarteritis, and parenchymal invasion

45. • Meningeal syphilis-onset of symptoms usually occurs <1 year after
infection
• headache, nausea, vomiting, neck stiffness, cranial nerve involvement,
seizures, and changes in mental status

46. • Meningovascular syphilis- symptoms usually occurs up to 10 years
after infection.
• Meningitis together with inflammatory vasculitis of small, medium,
or large vessels.
• The most common presentation is a stroke syndrome involving the
middle cerebral artery of a relatively young adult.

47. Parenchymatous syphilis
• GENERAL PARESIS
• Widespread late parenchymal damage
• Presents as progressive dementia beginning 15–20 years after original
infection
• The disease manifestation can be remembered by the mnemonic PARESIS

48. GENERAL PARESIS
• P: Personality
• A: Affect
• R: Reflexes (hyperactive)
• E: Eye (Argyll Robertson pupils)
• S: Sensorium (illusions, delusions, hallucinations)
• I: Intellect (decrease in recent memory, orientation, calculation,
• insight)
• S: Speech

49. DIAGNOSIS OF NEUROSYPHILIS
• CSF
• mononuclear pleocytosis (>5 white blood cells/μL),
• increased protein concentration (>45 mg/dL)
• CSF VDRL reactivity-gold standard for diagnosis of neurosyphilis.

50. TREATMENT
• Aqueous crystalline penicillin G -18–24 mU/d IV, given as 3–4 mU q4h or
continuous infusion for 10–14 days
• OR
• Aqueous procaine penicillin G 2.4 mU/d IM plus oral probenecid -500
mg qid-both for 10–14 days

51. DRUG-INDUCED COGNITIVE DYSFUNCTION
• Anticholinergic Drugs
• Anticonvulsants
• Antiparkinsonian Drugs
• Hypnotics/Sedatives
• Anti-hypertensives

52. Anticholinergic Drugs
• The higher the serum anticholinergic activity, the greater is the risk
of cognitive impairment.
• Elderly are more sensitive.
• Symptoms include
• Confusion and memory impairment
• Hallucinations
• Delirium
• Agitation

53. • Atropine
• Hyoscine
• Promethazine
• Dicycloverin
• Disopyramide
• Diphenhydramine
• cimetidine, ranitidine,
famotidine
• Scopolamine
• Antipsychotics-
Imipramine,Clomipramine
• Antipsychotics-
Chlorpromazine,Clozapine,Fluph
enazine

54. Anticonvulsants
• All anticonvulsants are capable of producing some degree of cognitive
dysfunction presenting as psychosis, confusion, or memory loss
• More significant cases have been reported with Primidone and
Phenobarbital
• Topiramate and Levetiracetam are also implicated in causing cognitive
dysfunction and psychosis respectively.

55. Antiparkinsonian Drugs
• Apart from anticholinergic agents, which are particularly likely to
cause cognitive dysfunction, all dopaminergic agents can cause
delirium and psychosis.
• Levodopa, Pramipexole, and Ropinirole,Amantadine.

56. Hypnotics/Sedatives
• All sedatives have the potential to produce cognitive impairment
• Benzodiazepines- most frequently contributing to delirium-development
of confusion and anterograde memory loss
• Elderly are more susceptible.

57. Anti-hypertensives
• Delirium has been more pronounced with Guanabenz, Clonidine, and
Methyldopa
• Beta blockers have moderate potential to cause delirium
• Diuretics, ACE inhibitors,CCB-low risk to cause delirium.

58. TREATMENT
• Withdrawal of the specific drug

59. Head trauma and diffuse brain
damage causing dementia
• Chronic subdural hematoma
• Normal-pressure hydrocephalus

60. NORMAL-PRESSURE HYDROCEPHALUS
• classic triad.
NPH
DEMENTIA
Urinary
incontinence
Gait disturbance

61. Clinical Signs
• Gait disturbances-typically the first signs
• Apraxic, bradykinetic, glue-footed, magnetic, parkinsonian and shuffling
gait.
• Cognitive deficits-subcortical type-psychomotor slowing, memory
impairment, and impaired executive function with preserved cortical
tests

62. Diagnosis
• clinical history-Patients often present with a history of falls.
• Neuroimaging- ventricular enlargement is necessary to establish the
diagnosis of NPH for patients with appropriate symptoms.
• Evans’ index-maximal frontal horn ventricular width divided by the
transverse inner diameter of the skull- if >0.3- suggestive of significant
ventriculomegaly.

63. Prognostic Tests
1. CSF tap test
2. External CSF drainage via spinal drainage
3. CSF outflow resistance determination.

64. CSF tap test
• The CSF tap test, also called a large-volume lumbar puncture,
involves the withdrawal of 40–50 mL of CSF by means of lumbar
puncture with symptoms assessed during the first 24 h after the
procedure-Symptomatic improvement after CSF removal increases the
likelihood of a favorable response to shunt placement.

65. • The treatment for NPH is surgical diversion of CSF-by implanting a
shunt to drain CSF to a distal site
• Although all symptoms can resolve following shunt surgery, gait is the
most likely to improve

66. Chronic Subdural Hematoma
• Subacutely evolving syndrome due to subdural hematoma occurs days
or weeks after injury with drowsiness, headache, confusion, or mild
hemiparesis, usually in the elderly with age-related atrophy and often
after only minor or unnoticed trauma.
• Headache,slowed thinking, vague change in personality,seizure, or a
mild hemiparesis.
• The headache typically fluctuates in severity, sometimes with changes in
head position.
• Drowsiness, inattentiveness, and incoherence of thought .

67. DIAGNOSIS AND TREATMENT
• History of trivial trauma that may not be recollected
• CT-Appear as crescentic clots over the convexity of one or both
hemispheres,most commonly in the FT region
• Treatment with surgical evacuation through burr holes is usually
successful, if a cranial drain is used postoperatively.