VAISHNAVI SURESH NAIR

MADNESS

A PROGRESSIVE DETERIORATION OF INTELLECT, BEHAVIOUR & PERSONALITY DUE TO DIFFUSE DISEASE OF CEREBRAL HEMISPHERE, MAXIMALLY AFFECTING THE CEREBRAL CORTEX & HIPPOCAMPUS.

DEMENTIA

COMMON SIGNS & SYMPTOMS

-MEMORY LOSS-IMPAIRED JUDGEMENT-DIFFICULT WITH ABSTRACT THINKING-FAULTY REASONING-INAPPROPRIATE BEHAVIOUR

-LOSS OF COMMUNICATION SKILLS-DISORIENTATION TO PLACE & TIME-GAIT, MOTOR & BALANCE PROBLEMS-NEGLECT OF PERSONAL CARE & SAFETY-HALLUCINATIONS,PARANOIA & AGITATION

RISK FACTORS FOR DEMENTIA

dementia

AGE (ABOVE 65)/SEX (MALE)/GENETIC

OVER WEIGHT/DRUG/SMOKING/ALCOHOL

BLOOD PRESSURE/BLOOD SUGAR/ CHOLESTEROL

DEPRESSION/STRESS

HEART DISEASES/DIABETES/VASCULAR DISEASES

HEAD INJURY/ INFLAMMATORY STRESS/TUMOR

HIV INFECTION/SOME IMMUNOLOGICAL DISORDERS

POOR EDUCATION/ LOW PHYSICAL ACTIVITY/POOR NUTRITION

• SYMPTOM RATHER THAN A SINGLE DISEASE ENTITY.• OCCURS IN ANY AGE,MORE COMMON IN ELDERLY AGE (ABOVE 65

YEARS).• IF OCCURRED UNDER 65, IT IS TERMED AS PRE-SENILE DEMENTIA.• INCIDENCE RATE: 187/100,000 PERSONS.• ACCELERATED BY CHANGE OF ENVIRONMENT, INTERCURRENT

INFECTIONS, SURGICAL PROCEDURES.

INTEROSPECTIVE:UNSURE OF SELF

DIFFICULTY IN COPING WITH WORK & DAILY ROUTINE(RETAINED INSIGHT)

LOSS OF INSIGHT,BEHAVIOURAL CHANGES,LOSS OF INHIBITION

LONG TERM CARE;CAN’T BE UN-ATTENDED

MUTISMINCONTINENCE,

DEATH.

DEVELOPMENT OF SYMPTOMS

CLASSIFICATION -BASED ON CAUSE1)ALZHEIMER’S DISEASE (60% OF ALL CASES)2)CEREBRO VASCULAR DISEASES (20% OF ALL CASES) - MULTI INFARCT (ATHEROSCLEROTIC) DEMENTIA - SUBCORTICAL VASCULAR DISEASE ( BINSWANGER’S DISEASE)

3)NEURO DEGENERATIVE - PICK’S DISEASE ; HUNTINGTON’S CHOREA ; PARKINSON’S DISEASE4)INFECTIONS- CREUTZFELD-JACKOB’S DISEASE ; HIV(AIDS DEMENTIA COMLEX) ; VIRAL ENCEPHALITIS ; PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY5)NORMAL PRESSURE HYDROCEPHALUS6)NUTRITIONAL -WERNICKE KORSAKOFF (THIAMINE DEFICIENCY); B12 DEFICIENCY; FOLIATE DEFICIENCY7)METABOLIC- HEPATIC DISEASE; THYROID DISEASE; PARATHYROID DISEASE; CUSHING’S SYNDROME8)CHRONIC INFLAMMATORY – COLLAGEN VASCULAR DISEASE & VASCULITIS, MULTIPLE SCLEROSIS9)TRAUMA – HEAD INJURY; PUNCH-DRUNK SYNDROME

10)TUMOR - eg: SUBFRONTAL MENINGOMA

SOME CASES ARE TREATABLE ; 10-15% ARE REVERSIBLE.

CLASSIFICATION -BASED ON SITE

# FRONTAL PREMOTOR CORTEX.

#BEHAVIOURAL CHANGES,LOSS OF INHIBITION,ANTI-SOCIAL BEHAVIOUR,FACILE & IRRESPONSIBLE

#Eg: NORMAL PRESSURE HYDROCPHALUS, HUNTINGTON’S CHOREA,METABOLIC DISEASE

ANTERIOR POSTERIOR#PARIETAL & TEMPORAL LOBES.

#DISTURBANCE OF COGNITIVE FUNCTION(MEMORY & LANGUAGE)WITHOUT MARKED CHANGE IN BEHAVIOUR.

#Eg: ALZHEIMER’S DISEASE.

SUB-CORTICAL CORTICAL

#APATHETIC

#FORGETFUL & SLOW, POOR ABILITY TO USE KNOWLEDGE

#ASSOCIATED WITH OTHER NEUROLOGICAL SIGNS & MOVEMENT DISORDERS.

#Eg: PARKINSON’S DISEASE, AIDS DEMENTIA COMPLEX.

# HIGHER CORTICAL ABNORMALITIES

#DYSPHASIA, AGNOSIA, APRAXIA

#Eg:ALZHEIMER’S DISEASE

Alzheimer’s disease:• Most common type of dementia; accounts for an estimated 60 to 80 percent of cases.

Symptoms:  Difficulty remembering names and recent events is often an early clinical symptom.

apathy and depression are also often early symptoms.

Later symptoms include impaired judgment, disorientation, confusion, behaviour changes and difficulty speaking, swallowing and walking.

Brain changes: 

=>Hallmark abnormalities are deposits of the protein fragment beta-amyloid (plaques) and twisted strands of the protein tau (tangles) as well as evidence of nerve cell damage and death in the brain.

Cerebrovascular dementia: Previously known as multi-infarct or post-stroke dementia, vascular dementia is the second most common cause of dementia after Alzheimer's disease.(20% Of all cases)

Eg:MULTI INFARCT DEMENTIA (ATHEROSCLEROTIC) , SUBCORTICAL VD (BINSWANGER’S DISEASE-SUBCORTICAL LEUCOENCEPHALOPATHY)

Symptoms: 

Impaired judgment or ability to plan steps needed to complete a task is more likely to be the initial symptom, as opposed to the memory loss often associated with the initial symptoms of Alzheimer's.

Occurs because of brain injuries such as microscopic bleeding and blood vessel blockage.

The location of the brain injury determines how the individual's thinking and physical functioning are affected

Brain changes: 

Brain imaging can often detect blood vessel problems implicated in vascular dementia.

As Parkinson's disease progresses, it often results in a progressive dementia similar to dementia with Lewy bodies or Alzheimer's.

Symptoms: 

Problems with movement are a common symptom early in the disease. If dementia develops, symptoms are often similar to dementia with Lewy bodies.

RESTING TREMOR, AKINETIC RIGIDITY,BENT POSTURE,HYPOMIMIA

Brain changes: 

Alpha-synuclein clumps are likely to begin in an area deep in the brain called the substantia nigra. These clumps are thought to cause degeneration of the nerve cells that produce dopamine.

Parkinson’s disease

Eg: PICK’S DISEASE , HUNTINGTON’S CHOREA , PARKINSON’S DISEASE

NEURO DEGENERATIVE DEMENTIA:

Pick’s disease presents with impairment of recent memory associated with entorhinal cortex and hippocampal

dysfunction, Pick disease typically affects the frontal and/or anterolateral temporal lobes.

A TYPE OF FRONTO-TEMPORAL DEMENTIA.

Emotional & behavioral changes, mutism, aphasia, echolalia(repeating whatever spoken to them), rigidity, apraxia, weakness, memory loss.

BRAIN CHANGES:

Pick disease is defined pathologically by severe atrophy, neuronal loss, and gliosis.

Frequently, Pick disease is accompanied by the occurrence of tau-positive inclusions. 

Swollen (ballooned) neurons (Pick cells) and argentophilic neuronal inclusions, known as Pick bodies, can disproportionally affect the frontal and temporal cortical regions. Fewer Pick bodies may be present in these regions if the primary symptoms are behavioral (behavioral variant), compared with the primary symptoms of aphasia.

Dementia caused by infections

CJD is the most common human form of a group of rare, fatal brain disorders affecting people and certain other mammals. Variant CJD (“mad cow disease”) occurs in cattle, and has been transmitted to people under certain circumstances.

Symptoms: Rapidly fatal disorder that impairs memory and coordination and causes behavior changes.

Brain changes: Results from misfolded prion protein that causes a "domino effect" in which prion protein throughout the

brain misfolds and thus malfunctions.

Eg: CREUTZFELD-JACOB DISEASE , HIV INFECTION (AIDS-DEMENTIA COMPLEX) , VIRAL ENCEPHALITIS , PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY

CREUTZFELD-JACOB DISEASE

HIV Infection (AIDS-Dementia complex) A condition that leads to the loss of intellectual abilities such as memory, judgment, and abstract

thinking. It can also cause changes in personality.

AIDS Dementia Complex (or ADC) is a type of dementia that occurs in advanced stages of AIDS (acquired immunodeficiency syndrome).

These are some of the first signs and symptoms of ADC:•Short attention span•Trouble remembering•Poor judgment•Slowed thinking and longer time needed to do tasks•Irritability•Unsteady gait, tremor, or trouble staying balanced•Poor hand coordination•Social withdrawal or depression

In later stages, you may have more severe symptoms:•Extreme mood swings•Psychosis•Loss of bladder and bowel control

Normal Pressure HydrocephalusSymptoms:  Symptoms include difficulty walking, memory loss and inability to control urination.

Brain changes:  Caused by the build up of fluid in the brain. Can sometimes be corrected with surgical

installation of a shunt in the brain to drain excess fluid.

NutritionalEg: WERNICKE-KORSAKOFF (THIAMINE DEFICIENCY), B12 DEFICIENCY , FOLIC ACID DEFICIENCY

Korsakoff syndrome is a chronic memory disorder caused by severe deficiency of thiamine (vitamin B-1). The most common cause is alcohol misuse.

Symptoms: Memory problems may be strikingly severe while other thinking and social skills seem

relatively unaffected.Brain changes: Thiamine helps brain cells produce energy from sugar. When thiamine levels fall too low, brain

cells cannot generate enough energy to function properly.

WERNICKE KORSAKOFF SYNDROME

By Metabolic disorders Eg: HEPATIC DISEASES, THYROID DISEASES, PARATHYROID DISEASES, CUSHING’S SYNDROME

Chronic inflammatory Eg: COLLAGEN VASCULAR DISEASE, VASCULITIS, MULTIPLE SCLEROSIS

Trauma Eg: HEAD INJURY, PUNCH-DRUNK SYNDROME

Punch-Drunk SyndromeA condition seen in boxers and alcoholics, caused by repeated cerebral concussions and

characterized by weakness in the lower limbs, unsteadiness of gait, slowness of muscular movements, hand tremors, hesitancy of speech, and mental dullness.

Boxer's encephalopathy, dementia pugilistica. A syndrome affecting 10–20% of professional boxers, which is the cumulative result of recurrent brain damage and progressive communicating hydrocephalus due to extrapyramidal and cerebellar lesions that translate into dysarthria, ataxia, tremors, pyramidal lesions–causing mental deterioration and personality changes–eg, rage reaction and morbid jealousy–'Othello syndrome'

Tumor Eg: SUBFRONTAL MENINGOMA

Dementia rarely may be due to intracranial tumour, especially when tumours occur in certain anatomical sites.

Mental or behavioral changes occur in 50-70% of all brain tumours as distinct from dementia which is associated with frontal lobe tumours, III ventricle tumours and corpus callosum tumours.

Cognitive impairment also occurs as a non metastatic complication of systemic malignancy.

DEMENTIA WITH LEWY BODY DISEASE (DLB)Symptoms:

 People with dementia with Lewy bodies often have memory loss and thinking problems common in Alzheimer's, but are more likely than people with Alzheimer's to have initial or early symptoms such as sleep disturbances, well-formed visual hallucinations, and muscle rigidity or other parkinsonian movement features.

Brain changes: 

Lewy bodies are abnormal aggregations (or clumps) of the protein Alpha- synuclein. When they develop in the brain cortex, dementia can result. Alpha- synuclein also aggregates in the brains of people with Parkinson's disease, but the aggregates may appear in a pattern that is different from dementia with Lewy bodies.

Other causes:DEMENTIA CAN OCCUR AS A SYMPTOM OF MORE WIDE SPREAD DEGENERATIVE DISORDERS Eg: HUNTINGTON’S DISEASE, DIFFUSE LEWY BODY DISEASE, PROGRESSIVE SUPRANUCLEAR PALSY, MOTOR NEURON DISEASE etc.

Huntington’s Disease Huntington’s disease is a progressive brain disorder caused by a single defective gene on

chromosome 4.

Symptoms: Include Huntington’s chorea, dysarthria, dysphagia, facial twitching, chameleon or

trombone tongue a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes.

Brain changes: The gene defect causes abnormalities in a brain protein that, over time, lead to worsening

symptoms.

Mixed Dementia In mixed dementia abnormalities linked to more than one type of dementia occur

simultaneously in the brain.

Brain changes:  Characterized by the hallmark abnormalities of more than one type of dementia —most

commonly, Alzheimer's and vascular dementia, but also other types, such as dementia with Lewy bodies.

HISTORY TAKING

NOTE:1) RATE OF INTELLECTUAL DECLINE2) IMPAIRMENT OF SOCIAL FUNCTION3) GENERAL HEALTH & RELEVANT DISORDERS (Eg: STROKE, HEAD INJURY)4) NUTRITION STATUS5) DRUG HISTORY6) FAMILY HISTORY OF DEMENTIA

- FROM PATIENT & RELATIVE

TESTS ASSIGNED TO CHECK INTELLECTUAL FUNCTIONS ARE DESIGNED TO CHECK: 1) MEMORY 2) ABSTRACT THOUGHT 3) JUDGEMENT 4) SPECIFIC HIGHER CORTICAL FUNCTIONS

IN EARLY / PSEUDO DEMENTIAS, A FORMAL ASSESSMENT FROM A CLINICAL PSYCHOLOGIST IS ADVISABLE

PHYSICAL EXAMINATIONNOTE: FOCAL SIGNS INVOLUNTARY MOVEMENTS PSEUDO BULBAR SIGNS PRIMITIVE REFLEXESCHECK: POUT REFLEX (Tap lips with a tendon hammer, a pout reflex is observed) GRASP REFLEX (Tapping in between eyes, patient can’t inhibit blinking in response to stimulation) GLABELLAR REFLEX (Stroking palm induces grip) PALMOMENTAL REFLEX (Quick scratch on palm induces sudden contraction of mentalis muscle in face)PRIMITIVE REFLEXES ARE PRESENT IN INFANCY & IN AGED PEOPLE, AS WELL AS IN DEMENTIANEUROPSYCHOMETRIC TEST (ASSESSMENT OF ONE’S COGNITIVE FUNCTIONS SUCH AS MEMORY, CONCENTRATION, PROBLEM SOLVING SKILLS) IS PERFORMED TO:

-DIAGNOSE EARLY DEMENTIA-SEPARATE TRUE DEMENTIA FROM PSEUDO DEMENTIA-MONITOR PROGRESS / TRIALS OF TREATMENT

DIAGNOSTIC APPROACH:

IMAGING MAINLY INCLUDES MRI , CT-SCAN , SPECT , PET etc.

LAB STUDIES INCLUDES CBC , ESR , THYROID HORMONE TEST, VIT-B12 BLOOD TEST , LIVER FUNCTION TEST (ALT,AST,BLOOD TEST) , HIV TEST, ELECTROLYTE TEST (TO CHECK KIDNEY FUNCTION), TOXICOLOGY SCREEN (DRUG) , ANTINUCLEAR ANTIBODIES (AUTOIMMUNE DISEASE) , LUMBAR PUNCTURE (To check some proteins in spinal fluid), LEAD TEST (to check heavy metals in blood) etc.

CONFIRMATION: USUALLY WITH AUTOPSY,BIOPSY.

Specimen in end stage AD demonstrating severe global atrophy. 

The images show FDG-PET and axial FLAIR images of a normal subject and of patients with AD and FTD.

In AD there is a decreased metabolism of the parietal lobes (yellow arrows), whereas in FTD, there is frontal hypometabolism (red arrows).

Presenile AD with normal hippocampus and severe parietal atrophy

AD

The images show a patient with a strategic PCA infarction involving the hippocampus.This type of infarct can result in sudden dementia if located in the dominant hemisphere.It will usually not result in dementia if it occurs in the non-dominant hemisphere.

Vascular Dementia (VaD)

The images are of a patient who had VaD, but the medial temporal lobe was normal.

MTA in a patient with VaD

End stage FTLD with striking atrophy of frontal and temporal lobes. No artophy of parietal and occipital lobes.

Cerebro Amyloid Angiopathy showing multiple peripherally located micro bleeds.

images of the same patient show Fazekas 2 white matter hyprintensities.

Fronto-temporal Lobar DegenerationCerebral Amyloid Angiopathy

Differential diagnosis:Dementia, delirium and depression are the 3 most prevalent mental disorders in the

elderly.

While dementia and depression are prevalent in the community, hospitals and nursing homes, delirium is seen most often in acute care hospitals.

The first step is to recognise which of the syndromes is present.

Dementia is defined by a chronic loss of intellectual or cognitive function of sufficient severity to interfere with social or occupational function.

Delirium is an acute disturbance of consciousness marked by an attention deficit and a change in cognitive function.(Hallucinations, autonomic over reactivity as a consequence of toxic, metabolic or infective conditions.

Depression is an affective disorder evidenced by a dysphoric mood, but the most pervasive symptom is a loss of ability to enjoy usual activities.

These syndromes are not mutually exclusive, as dementia frequently coexists with delirium and depression.

Diagnostic criteria for delirium

- Altered mental status (AMS) not explained by dementia.-AMS developed over a short period of time (hours to days) and fluctuates-AMS could be explained by a drug, acute illness or metabolic disturbance

Diagnostic criteria for dementia

-Memory loss, impairment of language, praxis, recognition or abstract thinking-Chronic and progressive-Delirium ruled out

Delirium is attention disorder vs. dementia which is a memory disorder.

In alcoholism before leaping into the diagnosis- WERNICKE KORASKOFF SYNDROME, we should also consider the chance of CHRONIC SUBDURAL HEMATOMA

PREVENTION

PEOPLE WHO HAVE DEMENTIA DUE TO STROKE, MAY BE ABLE TO PREVENT FUTURE DECLINES BYREDUCING THEIR RISK FOR HEART DISEASES.FOR Eg: 1)TREAT OR PREVENT HIGH BP 2)DON’T SMOKE 3)STAY AT A HELTHY WEIGHT (REDUCE RISK OF DIABETES) 4)KEEP YOUR CHOLESTEROL NORMAL RANGE 5)PROPER PHYSICAL ACTIVITY 6)STAY MENTALLY & SOCIALLY ACTIVE

TREATMENT

# Doctors use medicines to treat dementia in the following ways:

correct a condition that's causing dementia, such as thyroid replacement for hypothyroidism, vitamins for lack of vit-B12, or antibiotics for infections.

To maintain mental functioning for as long as possible when dementia cannot be reversed.

To prevent further strokes in people who have dementia caused by stroke (vascular dementia).

To manage mood or behaviour problems, such as depression, insomnia, hallucinations, and agitation.

=>CHOLINESTERASE INHIBITORS SUCH AS DONEPEZIL (ARICEPT),GALANTAMINE (REMINYL), & RIVASTIGMINE (EXELON) ARE DEVELOPED TO TREAT PRIMARILY ALZHEIMER’S , BUT ARE ALSO USED IN OTHER DEMENTIAS ESPECIALLY IN VASCULAR DEMENTIAS.

=>MEMENTINE (NAMENDA) USED TO TREAT THE SYMPTOMS OF ALZHEIMERS DISEASE, BUT MAY ALSO HELP WITH MILD-MODERATE VASCULAR DEMENTIA

=> IT IS NOT CLEAR THAT HOW LONG THESE MEDICINES WORK.

# MEDICINES TO HELP MAINTAIN MENTAL FUNCTIONS:

# CHANGING WHAT YOU EAT CAN REDUCE DEMENTIA SYMPTOMS & IMPROVE MENTAL CLARITY =>Reduce intake of carbs & sugars ; Take enough protein , vitamins-C,D,E,B12 , omega 3s fatty acid, zinc @ prescribed amount).

# MEDICINES TO CONTROL MOOD/BEHAVIOUR PROBLEMS => ANTI-PSYCHOTIC DRUGS: SUCH AS RISPERIDONE (RISPERDAL) , OLANZEPINE (ZYPREXIA) => ANTI-DEPRESSANTS: ESPECIALLY SELECTIVE SERETONIN REUPTAKE INHIBITORS

# MEDICINES TO PREVENT FUTURE STROKES=>DOCTORS PRESCRIBE MEDICINES FOR HIGH BP & CHOLESTEROL (THESE CAN’T REVERSE EXISTING DEMENTIA;BUT PREVENT FURTHERBRAIN DAMAGE DUE TO STROKES & HD)

Reference:• NEUROLOGY AND NEUROSURGERY ILLUSTRATED• http://www.webmd.com/alzheimers/tc/dementia• http://www.aplaceformom.com/blog/2013-02-01-diet-and-dementia/• http://www.recover101.com/dementia-treatment-long-short-term• http://apt.rcpsych.org/content/7/1/24.full• http://www.alz.org/dementia/types-of-dementia.asp• http://www.radiologyassistant.nl/en/p43dbf6d16f98d/dementia-role-of-mri.html• http://www.ncbi.nlm.nih.gov/pubmed/7858369

Thank you