DEMENTIA

Dr. WALID REDA ASHOUR, MD

DEFINITIONDEFINITION

DEFINITION: DEFINITION: It is progressive deterioration of It is progressive deterioration of

intellect (thinking and judgement), memory,intellect (thinking and judgement), memory,

behaviour and personality due to disease of the behaviour and personality due to disease of the

cerebral hemispheres.cerebral hemispheres.

• Dementia itself is a symptom, not a diagnosis. Dementia itself is a symptom, not a diagnosis.

Dementia is also defined as: Dementia is also defined as: acquired loss of acquired loss of

cognitive functioning, and occurs in clear cognitive functioning, and occurs in clear

consciousness. This distinguishes it from mental consciousness. This distinguishes it from mental

retardation/developmental delay and cases where retardation/developmental delay and cases where

consciousness is fluctuating or impaired, such as consciousness is fluctuating or impaired, such as

delirium or coma.delirium or coma.

CAUSES:CAUSES:

I. Dementia associated with systemic disease:I. Dementia associated with systemic disease:

- Hypothyroidism (cretinism). - Liver failure.- Hypothyroidism (cretinism). - Liver failure.

- Hypoparathyroidism. - Drug abuse.- Hypoparathyroidism. - Drug abuse.

- Cushing's syndrome. Cushing's syndrome.

- Deficiency diseases (vit. B1, B12, niacin).- Deficiency diseases (vit. B1, B12, niacin).

II. Idiopathic:II. Idiopathic:

- Alzheimer's disease.- Alzheimer's disease.

- Pick's disease.- Pick's disease.

III. Dementia associated with neurological disease:III. Dementia associated with neurological disease:

- Multi-infarction.- Multi-infarction.

- Tumors: e.g.: frontal lobe, temporal lobes, and - Tumors: e.g.: frontal lobe, temporal lobes, and

Corpus callosum.Corpus callosum.

- Encephalitis: e.g.: due to Herpes simplex and - Encephalitis: e.g.: due to Herpes simplex and

syphilis.syphilis.

- Degenerative: Huntington's chorea.- Degenerative: Huntington's chorea.

- Normal pressure hydrocephalus.- Normal pressure hydrocephalus.

CAUSES IICAUSES II

-Vascular:-Vascular: cerebral infarction, multiple strokes, cerebral infarction, multiple strokes,

diffuse white matter ischemia, bilateral thalamic diffuse white matter ischemia, bilateral thalamic

infarctions, amyeloid angiopathy.infarctions, amyeloid angiopathy.

-Infections:-Infections: neurosyphilis, chronic meningitis neurosyphilis, chronic meningitis

(tuberculous, fungus), AIDS, progressive (tuberculous, fungus), AIDS, progressive

multifocal leuko-encephalopathy, herpes simplex multifocal leuko-encephalopathy, herpes simplex

encephalitis, Curtzfeldt-Jacob disease, subacute encephalitis, Curtzfeldt-Jacob disease, subacute

sclerosing pan-encephalitis, Whipple’s disease.sclerosing pan-encephalitis, Whipple’s disease.

-Autoimmune: -Autoimmune: CNS vasculitis, SLE, MS,CNS vasculitis, SLE, MS,

Hashimoto’s encephalopathy.Hashimoto’s encephalopathy.

-Metabolic/Toxic: -Metabolic/Toxic: renal failure, dialysis, hepatic renal failure, dialysis, hepatic

failure ,chronicfailure ,chronic hypo-ventilation, hypo-ventilation,

hypothyroidism, hypocalcaemia, hypothyroidism, hypocalcaemia,

tranquilizers, alcohol, Vit. B12 deficiency, tranquilizers, alcohol, Vit. B12 deficiency,

nicotinic acid nicotinic acid

deficiency, lead, carbon monoxidedeficiency, lead, carbon monoxide

-Idiopathic/inherited: -Idiopathic/inherited: AD, HD, PD, DLB, FTD, PSP, AD, HD, PD, DLB, FTD, PSP,

CBD, TGA. CBD, TGA.

-Neoplasm: -Neoplasm: brain tumors, meningeal brain tumors, meningeal

carcinomatosis, para-neoplastic, post-radiation. carcinomatosis, para-neoplastic, post-radiation.

-Traumatic:-Traumatic: head injury, subdural hematoma.head injury, subdural hematoma.

THE COMMON TYPES OF DEMENTING DISEASESTHE COMMON TYPES OF DEMENTING DISEASES

1- Cerebral atrophy1- Cerebral atrophy, mainly , mainly AlzheimerAlzheimer but including Lewy-body, but including Lewy-body,

Parkinson, frontotemporal, and Pick diseases.Parkinson, frontotemporal, and Pick diseases.

2- Multiinfarct dementia. 2- Multiinfarct dementia. 3- Alcoholic dementia.3- Alcoholic dementia. 4- Intracranial 4- Intracranial

tumors. tumors.

5- Normal-pressure hydrocephalus. 6- Huntington chorea. 5- Normal-pressure hydrocephalus. 6- Huntington chorea.

7- Chronic drug intoxications. 7- Chronic drug intoxications.

8-Miscellaneous diseases 8-Miscellaneous diseases (hepatic failure; pernicious anemia; (hepatic failure; pernicious anemia;

hypo- or hyperthyroidism; dementias with amyotrophic lateral hypo- or hyperthyroidism; dementias with amyotrophic lateral

sclerosis, cerebellar atrophy; neurosyphilis; Cushing syndrome, sclerosis, cerebellar atrophy; neurosyphilis; Cushing syndrome,

Creutzfeldt-Jakob disease; multiple sclerosis; epilepsy)Creutzfeldt-Jakob disease; multiple sclerosis; epilepsy)

9- Cerebral trauma. 10- AIDS dementia. 11- Pseudo-dementias9- Cerebral trauma. 10- AIDS dementia. 11- Pseudo-dementias

(depression, hypomania, schizophrenia, hysteria, undiagnosed)(depression, hypomania, schizophrenia, hysteria, undiagnosed)

CLINICAL PICTURE

CLINICAL PICTURE:CLINICAL PICTURE:

1. Dementia may occur at any age, but is more common 1. Dementia may occur at any age, but is more common

in the elderly.in the elderly.

2. The rate of progression depends on the cause. 2. The rate of progression depends on the cause.

Alzheimer's disease progresses slowly over years, Alzheimer's disease progresses slowly over years,

while dementia 2ry to encephalitis may be rapid over while dementia 2ry to encephalitis may be rapid over

weeks.weeks.

3. The patient finds increasing difficulty in performing 3. The patient finds increasing difficulty in performing

his usual work and social activities. At first he is his usual work and social activities. At first he is

aware of his disability then loses this awareness.aware of his disability then loses this awareness.

Behavioural and personality changes with loss of Behavioural and personality changes with loss of

initiation follow but the patient denies any initiation follow but the patient denies any

abnormality.abnormality.

In late stages the patient cannot be left unattended In late stages the patient cannot be left unattended

and the case ends with mutism and incontinence.and the case ends with mutism and incontinence.

4. The 4. The primitive reflexes primitive reflexes which are normally inhibited which are normally inhibited

and absent may reappear e.g.grasp, Groping, and absent may reappear e.g.grasp, Groping,

Glabellar, Pouting and Palmo-mental reflexes.Glabellar, Pouting and Palmo-mental reflexes.

• Grasp reflex: Grasp reflex: when an object touches the palm of when an object touches the palm of

the hand, the hand closes on it (grasps).the hand, the hand closes on it (grasps).

• Groping reflex: Groping reflex: when an object is moved in front of when an object is moved in front of

the eyes, the hand reaches out (gropes) for it.the eyes, the hand reaches out (gropes) for it.

• Glabellar reflex.Glabellar reflex.

• Pouting reflex: Pouting reflex: tapping the lips with a hammer tapping the lips with a hammer

results in a pout response.results in a pout response.

• Palmo-mental reflex: Palmo-mental reflex: a quick scratch on the palm a quick scratch on the palm

of the hand results in a sudden contraction of the of the hand results in a sudden contraction of the

mentalis muscle in the chin.mentalis muscle in the chin.

Alzheimer's disease (AD)Alzheimer's disease (AD)

Alzheimer's disease (AD) Alzheimer's disease (AD)

A progressive neurodegenerative disease that accounts for more A progressive neurodegenerative disease that accounts for more

than two-thirds of all cases of dementia. The most important risk than two-thirds of all cases of dementia. The most important risk

factor for AD is age, followed by an APOE4 genotype.factor for AD is age, followed by an APOE4 genotype.

II- Risk factors for Alzheimer diseaseII- Risk factors for Alzheimer disease

A- Advancing age is the greatest risk factorA- Advancing age is the greatest risk factor, but AD is not a typical , but AD is not a typical

part of aging. Most patients with AD are diagnosed at age 65 or part of aging. Most patients with AD are diagnosed at age 65 or

older. older.

B- Family History: B- Family History: Individuals who have a parent, brother or sister Individuals who have a parent, brother or sister

with AD are more likely to develop the disease.with AD are more likely to develop the disease.

C- Apolipoprotein E-e4 (APOE-e4) Gene: C- Apolipoprotein E-e4 (APOE-e4) Gene: increases the increases the

risk of developing AD and of developing it at a risk of developing AD and of developing it at a

younger age. younger age.

D- Mild Cognitive Impairment (MCI). D- Mild Cognitive Impairment (MCI).

E- Cardiovascular Disease Risk Factors: E- Cardiovascular Disease Risk Factors: Growing Growing

evidence suggests that the health of the brain is evidence suggests that the health of the brain is

closely linked to the overall health of the heart and closely linked to the overall health of the heart and

blood vessels. factors include blood vessels. factors include smoking, obesity, smoking, obesity,

diabetes, high cholesterol diabetes, high cholesterol and and hypertensionhypertension. Unlike . Unlike

genetic risk factors, many of these cardiovascular genetic risk factors, many of these cardiovascular

disease risk factors are disease risk factors are modifiablemodifiable..

• F- Education: F- Education: People with fewer years of education are at higher People with fewer years of education are at higher

risk for AD and other dementias. Having more years of risk for AD and other dementias. Having more years of

education builds a education builds a “COGNITIVE RESERVE” “COGNITIVE RESERVE” that enables that enables

individuals to better compensate for changes in the brain that individuals to better compensate for changes in the brain that

could result in symptoms of AD.could result in symptoms of AD.

• G- Social and Cognitive Engagement: G- Social and Cognitive Engagement: remaining mentally and remaining mentally and

socially active, may support brain health and possibly reduce socially active, may support brain health and possibly reduce

the risk of AD.the risk of AD.

• H- Traumatic Brain Injury (TBI): H- Traumatic Brain Injury (TBI): Moderate and severe TBI Moderate and severe TBI

increase the risk of developing AD. TBI is defined as a head increase the risk of developing AD. TBI is defined as a head

injury resulting in loss of consciousness or post-traumatic injury resulting in loss of consciousness or post-traumatic

amnesia that lasts more than 30 minutes. If loss of amnesia that lasts more than 30 minutes. If loss of

consciousness or post-traumatic amnesia lasts more than 24 consciousness or post-traumatic amnesia lasts more than 24

hours, the injury is considered severe.hours, the injury is considered severe.

Stages of ADStages of AD

1- Preclinical AD: 1- Preclinical AD: In this stage, individuals have measurable In this stage, individuals have measurable

changes in the brain, (CSF) and/or blood (biomarkers) that changes in the brain, (CSF) and/or blood (biomarkers) that

indicate the earliest signs of disease, but they have not yet indicate the earliest signs of disease, but they have not yet

developed symptoms such as memory loss. developed symptoms such as memory loss.

2- MCI due to AD: 2- MCI due to AD: Individuals with MCI have mild but Individuals with MCI have mild but

measurable changes in thinking abilities that are measurable changes in thinking abilities that are

noticeable to the person affected and to family members noticeable to the person affected and to family members

and friends, but that do not affect the individual’s ability to and friends, but that do not affect the individual’s ability to

carry out everyday activities. carry out everyday activities.

• As many as 15 percent of patients with MCI symptoms As many as 15 percent of patients with MCI symptoms

develop dementia each year. develop dementia each year.

3- Dementia due to AD: 3- Dementia due to AD: This stage is characterized by memory, This stage is characterized by memory,

thinking and behavioral symptoms that impair a person’s ability thinking and behavioral symptoms that impair a person’s ability

to function in daily life and that are caused by AD related brain to function in daily life and that are caused by AD related brain

changes.changes.

Symptoms of ADSymptoms of AD

• Alzheimer disease affects people in different ways. The most Alzheimer disease affects people in different ways. The most

common symptom pattern begins with a gradually worsening common symptom pattern begins with a gradually worsening

ability to remember new information. This occurs because the ability to remember new information. This occurs because the

first neurons to be lost and malfunction are usually neurons in first neurons to be lost and malfunction are usually neurons in

brain regions involved in forming new memories. As neurons in brain regions involved in forming new memories. As neurons in

other parts of the brain malfunction and lost, patients other parts of the brain malfunction and lost, patients

experience other difficulties. experience other difficulties.

common symptoms of AD: common symptoms of AD:

• • Memory loss that disrupts daily life. Memory loss that disrupts daily life. The gradual The gradual

development of forgetfulness is the major symptom. Small development of forgetfulness is the major symptom. Small

day-to-day happenings are not remembered. Seldom-used day-to-day happenings are not remembered. Seldom-used

names become particularly elusive. Little used words from names become particularly elusive. Little used words from

an earlier period of life also tend to be lost. Appointments an earlier period of life also tend to be lost. Appointments

are forgotten and possessions misplaced. Questions are are forgotten and possessions misplaced. Questions are

repeated again and again, the patient having forgotten repeated again and again, the patient having forgotten

what was just discussed. what was just discussed.

• Once the memory disorder has become pronounced, other Once the memory disorder has become pronounced, other

failures in cerebral function become increasingly apparent: failures in cerebral function become increasingly apparent: • •

Challenges in planning or solving problems. Challenges in planning or solving problems.

• • Difficulty completing familiar tasks Difficulty completing familiar tasks at home, at work or at at home, at work or at

leisure. leisure.

• • Confusion with time or place. Confusion with time or place.

• • Trouble understanding visual images and spatial relationships.Trouble understanding visual images and spatial relationships.

• • Misplacing things and losing the ability to retrace steps. Misplacing things and losing the ability to retrace steps.

• • Decreased or poor judgment. • Withdrawal from work or social Decreased or poor judgment. • Withdrawal from work or social

activities. • Changes in mood and personality. • Problems with activities. • Changes in mood and personality. • Problems with

words in speaking or writing. Finally, after many years of illness, words in speaking or writing. Finally, after many years of illness,

there is a failure to speak in full sentencesthere is a failure to speak in full sentences

THANK YOU

Treatment of ADTreatment of AD

1. Symptomatic Treatments:1. Symptomatic Treatments:

- Acetylcholinesterase Inhibitors- Acetylcholinesterase Inhibitors

- NMDA-receptor Antagonists- NMDA-receptor Antagonists

- Nicotinic-receptor Agonists- Nicotinic-receptor Agonists

2. Disease-modifying Treatments:2. Disease-modifying Treatments:

- Inhibition of amyloid formation: beta and gamma-secretase - Inhibition of amyloid formation: beta and gamma-secretase

inhibitors.inhibitors.

- Inhibition of abeta aggregation.- Inhibition of abeta aggregation.

- Tau phosphorylation inhibitors. - Tau phosphorylation inhibitors.

CLASSIFICATION OF THE AMNESIC STATESCLASSIFICATION OF THE AMNESIC STATES

I. Amnesic syndrome of sudden onset - usually with gradual but incomplete I. Amnesic syndrome of sudden onset - usually with gradual but incomplete

recovery:recovery:

• A. Bilateral or left (dominant) hippocampal infarction.A. Bilateral or left (dominant) hippocampal infarction.

• B. Bilateral or left (dominant) infarction of anteromedial thalamic nuclei.B. Bilateral or left (dominant) infarction of anteromedial thalamic nuclei.

• C. Infarction of the basal forebrain.C. Infarction of the basal forebrain.

• D. Subarachnoid hemorrhage (usually rupture of anterior communicating D. Subarachnoid hemorrhage (usually rupture of anterior communicating

artery aneurysm).artery aneurysm).

• E. Trauma to the diencephalic, inferomedial temporal, or orbitofrontal E. Trauma to the diencephalic, inferomedial temporal, or orbitofrontal

regionsregions

• F. Cardiac arrest, carbon monoxide poisoning, and other hypoxic states F. Cardiac arrest, carbon monoxide poisoning, and other hypoxic states

(hippocampal damage).(hippocampal damage).

• G. Following prolonged status epilepticus.G. Following prolonged status epilepticus.

• H. Following delirium tremens.H. Following delirium tremens.

II. Amnesia of sudden onset and short durationII. Amnesia of sudden onset and short duration

A. Temporal lobe seizures.A. Temporal lobe seizures.

B. Postconcussive states.B. Postconcussive states.

C. Transient global amnesia.C. Transient global amnesia.

D. Hysteria.D. Hysteria.

III. Amnesic syndrome of subacute onset with varying III. Amnesic syndrome of subacute onset with varying

degrees of recovery, usually leaving permanent residuadegrees of recovery, usually leaving permanent residua

A. Wernicke-Korsakoff syndrome.A. Wernicke-Korsakoff syndrome.

B. Herpes simplex encephalitis.B. Herpes simplex encephalitis.

C. Tuberculous and other forms of meningitis.C. Tuberculous and other forms of meningitis.

IV. Slowly progressive amnesic statesIV. Slowly progressive amnesic states

• A. Tumors involving the floor and walls of the third A. Tumors involving the floor and walls of the third

ventricle and limbic cortical structuresventricle and limbic cortical structures

• B. Alzheimer disease (early stage) and other degenerativeB. Alzheimer disease (early stage) and other degenerative

• disorders with disproportionate affection of the temporal disorders with disproportionate affection of the temporal

lobeslobes

• C. Paraneoplastic and other forms of immune “limbic” C. Paraneoplastic and other forms of immune “limbic”

encephalitisencephalitis

yyyyyyyyyyyyyyyyyy