DEMETIA

MEMORY IS THE RECORDING, RETENTION &RETRIEVAL OF

KNOWLEDGE

DISORDER OF MEMORY

• DEMENTIA: acquired and persistent compromise in multiple cognitive domains that is severe enough to interfere with everyday functioning

• IN ADDITION TO MEMORY IMPAIRMENT AT LEAST ONE OF FOLLOWING MUST OCCURE:

• APHASIA• AGNOSIA • DIORDER OF EXECUTIVE FUNCTION.

DEMENTIA

• COGNITIVE DEFICIT MUST BE SUFFICIENTLY SEVERE TO CAUSE IMPAIRMENT IN

• OCCUPATIONAL OR • SOCIAL ACTIVITY OF DAILY LIVING.

2-DEMENTIA

CLINICAL SYNDROME OF MEMORY DISFUNCTION

• DEMENTIA: • 1-LOSS OF MULTIPLE ACQUIRED

COGNITIVE &EMOTIONAL ABILITY SUFFICIENT TO INTERFER WITH DAILY ACTIVITY.

• 2- INCIDIOUS IN ONSET ,PROGRESSIVE• 3- AGE ASSOCIATED 1% IN 60 and doubles

every 5 years 30-50% in 85 years

HX

• Few definitive tests are available for diagnosing dementing disorders,

• so reliable historical information regarding the :

• onset,• course, and• associated features of cognitive

dysfunction is the cornerstone of differential diagnosis.

Historical Components of the Dementia Evaluation

INITIAL MANIFESTATIONS• Impaired recent memory (repeats self, forgets what was heard or

read, misplaces things)• Poor decision-making, judgment, or problem-solving; decreased

organizational skills• Difficulty learning new tasks or performing routine tasks• Problems managing money (balancing checkbook, forgetting to• pay bills) or household• Difficulties expressing self (word finding) or participating in• conversation• Getting lost in familiar areas, forgetting known routes while driving• Change in personality (apathetic, disinhibited), mood (sad,• irritable), or behavior (odd or bizarre)

Historical Components of the Dementia Evaluation

TEMPORAL FACTORS• Mode of onset (acute , subacute, insidious)• Course (static progressive, improvement over time,

fluctuating) INDIVIDUAL FACTORS• Cultural background• Educational level• Social/occupational demands (and changes incurred by• symptoms)• Life circumstances (social, financial, occupational, living

arrangements)• Premorbid personality characteristics

Historical Components of the Dementia Evaluation

HEREDITARY FACTORS• Familial risk factors (stroke, hypertension,

diabetes mellitus)• Genetic: family history suggesting

autosomal dominant inheritance or multiple cases in family suggesting non-mutation associated familial disease (e.g., apolipoprotein E4-associated Alzheimer's disease)

Historical Components of the Dementia Evaluation

MEDICAUNEUROLOGICAL CONDITIONS• General medical conditions (hypothyroidism,

hypertension, diabetes mellitus , heart disease)• Neurological conditions (transient ischemic attacks,

strokes, seizures , syncope, head trauma)• Associated motor features (tremor, gait difficulties,

speech/swallowing disturbance, ataxia)• Sleep disturbances (sleep apnea, insomnia, sleep-

associated movement disorder)

Evaluation

• Cognitive Assessment• Neuropsychiatric Assessment• Laboratory Evaluation• Neuroimaging

EXAMINATION OF AMEMORY

• MINI MENTAL STATUS EXAMINATION(MMSE)• Detection of IMMEDIATE , LONG TERM ,

REMOTE Memory • GENERAL &NEUROLOGIC EXAM

EVALUATION OF MEMORY

• Problem in IMMEDIATE MEMORY:• Attention ororintation cause immediate

memory deficit • IMMEDIATE: repeat aseries of random

digit.• Spared in SEVER AMNESIA & mild

DEMENTIA

EXAM OF MEMORY

• LONG TERM MEMORY(SHORT TERM MEMORY): remember and recall after 3 MINUTES

• Remote MEMORY(LONG TERM MEMORY): RECALL OF PAST PERSONAL , GEOGRAPHICAL OR HISTORICAL TEST.

EXAM OF MEMORYmotor , reflex, cerebellar, gait

• (CHOREA HUNTINGTON • TREMOR , RIGIDITY, POSTURAL REFLEX

IMPAIRMENT PARKINSON• MYOCLONUS POST ANOXIC, PRION• PRIMITIVE REFLEX BILATERAL

CORTICAL , SUBCORTICAL AND BRAINSTEM • ATAXIA & CEREBELLAR WERNIKE • KORSAKOFE• CRANIAL NERVE &HEMIPARASIS STROKE

EXAM OF MEMORY

• SENSORY EXAM IS DIFFICULT• DEFICIT IN HIGH CORTICAL FUNCTION

(AGNOSIA, NEGLECT EXTINCTION :,CORTICAL LESION

• VIBRATION &POSITION SENSE IMPAIRMENT VIT B12 DEFICIENCY

• LOSS OF PAIN & TEM. WITH PAIN CRISIS SYPHILITIC

ASSOCIATED MEDICAL FINDING

• THYROID DYSFUNCTION• VIT B12 DEFICIENCY• TOXICITY OF ANTICHOLINERGIC• WITHDRAWAL OF ALCHOL&SEDATIVE• HEPATIC DISEASE • TRAUMA • MENINGITIS, SAH, NPH,

INTRACRANIAL MASS

EVALUATION OF MEMORY

• CT SCAN• MRI, functional MRI(DETECT SOL, • DIFFUSE ATROPHY ALZHEIMER,• FOCAL ATROPHY PICK,S • PET (positron emission tomography, SPECT

(single positron emission computed tomography) asses global metabolic patterns

• diffuse neuronal loss on degenerative

EVALUATION OF MEMORY

• ELECTROPHYSIOLOGY USE FUL TO DETECT :

• 1-EPILEPSY, • 2-SLEEP DISORDER THAT RESULT TO

MEMORY PROBLEM• 3-DIFFUSE &NONSPECIFIC SLOWING • 4- PERIODIC PATTERN • 5-TRIPHASIC, OR BURST

SUPPERATION in PRION

EVALUATION

• FLUID &TISSUE ANALYSIS• 1-cbcdiff• 2- LFT • 3- TFT, • 4-DRUG ANALYSIS IN TOXICATION, • 5-TEST FOR CHRONIC MEMINGITIS,

CARCINOMA• 6- RECTAL BIOPSY AMILOIDOSIS

EVALUATION

• 7-BRAIN BIOPSY (VASCULITIS, PRION, INFECTION …)

• 8-CSF

EVALUATION OF MEMORY

• GENETIC TEST : • HUNTINGTON , ATYPICAL ALZHEIMER,

DEMENTIA• ALZHEIMER 70%0F DEMENTIA • VASCULAR 10 -20% OF dementia• ALCHOL DEMENTIA • INTRACRANIAL TUMOR• NORMAL PRESSURE HYDROCEPHALUS• CHRONIC DRUG INTOXICATION , METABOLIC• INFECTION (PRION)• OTHER NEUROLOGIC (PARKINSON, HUNTIONGTON,

SUPRANUCLEAR PALSY• PSEUDODEMENTIAI

DEMENTIA(reversible)

1-inflammatory: sarcoidosis , SLE, vasculitis(primary &secondary) 2- meningitis due to fungi, TB, listeria monocytosis, lyme. Syphilis, whipple 3 -VIT B12 deficiency 4 - toxics(drugs) 5- mass lesion (tumor, hematom ,communication hydrocephalus 6-coplex partial STATUS epilepticus

DEMENTIA(irreversible)

• 1- DEGENERATIVE (Alzeheimer, PICK,S huntington, parkinson, lewy body…)

• 2-VASCULAR(multiinfarct dementia, intra vascular coagulation)

• 3- METABOLIC: storage disease, leukodystrophy)

• 4- NEOPLASTIC( meningeal metastasis ,gliomatosis cerebri)

NEUROTRANSMITTER OF MEMORY

• CHOLINERGIC SYSTEM: has a critica l role in longterm memory

• SCOPOLAMINE(cholinergic antagonist) impaire memory

• PHYSIOSTIGINE(cholinergic agonist) faciliate memory performance

• CATHECHOLAMINE : important role in working memory

ALZEHEIMER( risk factor)

• Age(Prevalance): >60 years 5%• >85years 20-50%• Life time of developing AD is 12-17%• Alzheimer is sporadic , genetics basis 5%• Familial Alzheimer is AD : mutation in the APP

( chromosome 21) presenilin 1 ( chromosome 14 ) , presenilin 2 , APoe €4

• Others:Limited education, depression,gender, strogen replacement, head trauma, history of thyroid disease.

Alzehiemer(clinical features)

• 1-Memory loss (recent involved.• 2- aphasia (wernike)• 3- apraxia• 4- agnosia (a nosognosia,

prosopagnosia,• a topoghraphagnosia)

Alzeheimer(clinical symptomes)

• 5-Psychiatric symptoms • (depression,psychotic symptom• Paranoid delusion , and hallucination.• 6-Vegetative symptoms(sleep

disturbance, incontinence)• 7-Later bed ridden

Alzeiheimer(pathogenesis)

• 1- CORTICAL ATROPHY• 2- NEUROTIC (senile)PLAQUES, that is

amyloid surroded by dystrophic neuritis• 3- NEUROFIBRILLARY TANGLE(paired

hellicalfillaments.)• Filaments are major constituent of NFT, ,

neuropil treads, dystrophic neuritis.

Alzeheimer(pathogenesis)

• AD disrupts cortical input to hippcampus from association and limbic structure

• &• DISRUPTS HIPPOCAMPAL OUT FLOW

FROM Amomonis , subiculum to association cortex , diencephalon, basal forebrain and amygdala.

•

Alzeheimer( pathogenesis)

• ALZEHEIMER disconnect the hippocampus from its major

• INPUT & OUT PUT pathways, • BECAUSE

• HIPPOCAMAL FORMATION ARE INVOLVED EARLY IN AD.

Alzeheimer (management)

• 1-MEMORY TONIC: central acetylcholinestrase inhibitor:

TACRIN, EXELON MILD &MODERATE STAGE OF DISEASE

• 2-HALLOPERIDOL FOR DELUSION • 3-SEROTONIN REUPTAKE INHIBITOR

FOR DEPRESSION

MCI

• The most studied form of MCI is that of isolated recent memory loss, or amnestic MCI.

• Diagnostic criteria are as follows:1-a subjective or objective impairment in recent

memory, 2-relatively preserved cognitive functions in

other domains,3- and presence of normally performed everyday

activities of daily living..

MCI• Persons who present with amnestic MCI have an increased risk of

developing diagnosable AD at rates of 12% to 15% per year, in contrast with I% to 2% per year in age-matched normal subjects.

• Increased risk of more rapid transition or "conversion“ to AD includes:

significant hippocampal atrophy on MRI, worsened performance on recent memory testing, Elevated CSF tau and reduced A~-42 in the CSF, and the presence of an apoE4 allele

Alz PET

FTD• onset typically between the ages of 50 and

60 years• and featuring insidious personality change,

disinhibition, and subsequent gradual loss of speech output. Approximately 50% of the cases were familial.

• Amyloid PLAQUES and NEUROFIBRILLARY TANGLE not seen.

• FTD as a tauopathy• No treatment.

NPH

NPH

• Clinical triad ( gait apraxia , dementia , incontinency )

• Ivestigation : LP, Imaging• Tretment : Shunt • Complication of shunt

Creutzfeldt-Iakob Disease

• clinical presentation includes:• rapidly progressive dementia, myoclonus, • Other clinical sign : involvement of

cerebral cortex , cerebellum , basal ganglia brainstem and splinal cortex

• Psychiatric symptom • Pathogenesis : proteinaceous infectious

paticle ( prion )

CJD

• Investigation studies :EEGLP ( 14-3-3 pr )MRIBiopsy ( Pr Psc)• treatment : no treatment

DLB

• Second most common cause of dementia • Clinical : cogition decline without prominent memory

impairment Visual hallucination Parkinsonism Note : well respond to anticholinestrase but sensetive to antipsychotic drugs

Dementia with NEUROLOGIC sign

• HUNTINGTON:dominant inheritence• chore athetosi• dementia • parkinson: tremor• rigidity• bradykinesia • Dementia (10-15%)-

Dementia with neurologic sign

• Progressive supra nuclear palsy: • falling • Axiall dystonia• pseudobulbar palsy• supra nuclear ophthalmoplegia

DEMENTIA WITH NEUROLOGIC SIGN

• AIDS DEMENTIA COMPLEX• DEMENTIA • ATAXIA• SACCADIC &PURSUIT MOVEMENT

• upper motor sign• Incontinence • NEUROSYPHLIS (GENERAL PARESIS