Dementia : undergraduate (Alzheimer & vasular dementia)

1. Dementia
Dr Mohamed Rizk Khodair
Lecturer of neurology
October 6 university

2. Dementia is clinical impairment of multiple domains of cognitive function, which must include memory, in a patient
who remains alert with normal arousal, being severe to interfere with social and occupational function.

3. Etiologic Classification
A. Irreversible Degenerative Causes (Neurodegenerative Dementing Diseases or Primary Organic Dementias):
Incurable, Invariably Progressive, Ultimately Fatal.
1) Degenerative: Alzheimer’s disease (AD), Pick's disease, asymmetrical cortical degeneration syndromes
(ACDS), diffuse Lewy body dementia (DLBD), progressive supranuclear palsy (PSP), Huntington's disease
(HD), Parkinson's disease (PD).
2) Vascular: multi-infarct dementia, Binswanger disease.
3) Metabolic: storage diseases, leukodystrophies, Wilson disease, aluminum (dialysis dementia).
4) Neoplastic: meningeal metastases, gliomatosis cerebri.
5) Infectious (in young patients): prion diseases (Creutzfeldt-Jakob disease, etc.), HIV.
6) Trauma.
N.B. Degenerative Dementia implies disease progression over

4. B.Potentially Reversible Nondegenerative Causes
(Truly Chronic Encephalopathies or Secondary Dementias):
(Treatable causes)
1) Inflammatory: chronic inflammatory meningoencephalitis (CIME), sarcoidosis, CNS vasculitis’s, CNS
complications of SLE, paraneoplastic limbic encephalitis.
2) Infectious: chronic meningitis due to fungi, tuberculosis, Listeria monocytogenes, Lyme disease, neurosyphilis
(general paresis), CNS Whipple's disease.
3) Nutritional: vitamin B12 deficiency (also folate, thiamine, nicotinic acid deficiencies).
4) Metabolic: hepatic, renal, pulmonary failures, hypercalcemia.
5) Toxic: drugs (barbiturates, digoxin, anticholinergics), alcohol.
6) Mass lesion: subdural hematoma, normal-pressure hydrocephalus, meningioma, and other tumors (esp. In frontal
areas).
7) Complex partial status epilepticus.
Dementia is not part of normal aging and always represents pathologic process!!!
Dementia is symptom – always has cause!
Of all dementias, 20% are potentially reversible!

5. Neurodegenerative Dementing Diseases (irreversible chronic progressive
encephalopathies) fall into three broad categories:
I. Cortical Dementia
1. Alzheimer's Disease – major cortical degenerative disease!
2. Asymmetrical Cortical Degeneration Syndromes (e.g., Pick’s disease [frontotemporal dementia])
3. ALS-Dementia Complex - frontotemporal dementia with motor neuron disease (progression is more rapid than in AD - death
within 3 to 5 years); some argue that it is not distinct etiologic entity.
II. Subcortical Dementia
1. Parkinson's Disease with Dementia
2. Huntington's Disease
3. Multiple System Atrophy
4. Progressive Supranuclear Palsy
N.B. HIV encephalopathy (AIDS-dementia complex) is also subcortical dementia!
III. Mixed (Cortical-Subcortical) Dementia
1. Corticobasal Ganglionic Degeneration
2. Diffuse Lewy Body Disease

6. Features Cortical Subcortical
Examples Alzheimer’s disease Parkinson’s disease
Basic function deficit Specific deficits (apraxia, agnosia, aphasia) Impaired information processing and executive
function
Memory impairment Poor recognition, learning deficit Recall aided by cues, retrieval deficit
Depression Uncommon Common
Lesions Cortical association areas and mesiotemporal
limbic system
Subcortical structures and fronto-sub-cortical
circuitry
Speed of cognition Normal Slow
Speech Normal Abnormal (hypophonic, mute, dysarthric)
Language Aphasic Normal

7. Features Delirium dementia
onset Sudden- hours/days Insidious and slow
Cause Another medical emergency Baseline CNS disease-
neurodegenerative
course Reversible Progressive, irreversible
Memory impairment Impaired initially may be unable to recall
the incident
Initially lost of short-term memory
degree of memory loss increases as
the disease progresses
Attention Impaired initially Usually preserved may be impaired in
advanced stages
Orientation Impaired initially Usually preserved may be impaired in
advanced stages
Behavior Agitated/somnolent Usually normal, may be impaired in
advanced stages

8. Pseudodementia:
treatable / psychiatric disorder that mimics dementia (most common is
depression).
 depressed patients demonstrate little effort at tasks and answer "I don't know"
to direct questions (vs. demented patients are cooperative and struggle to
perform various tasks).

9. General investigation of dementia
1. Cognitive assessment:
 The mini mental state examination (MMSE) or folstein test is a brief 30-point questionnaire test that is used to screen for cognitive impairment.
If< 24 cognitive impairment.
 Montreal cognitive assessment: rapid screening instrument for mild cognitive dysfunction.
2. Neuropsychological assessment:
 Differentiate diseases that have neuropsychiatric disease symptoms as Alzheimer disease and frontotemporal dementia.
 Differentiate between dementia and psychiatric diseases as depression.
3. Routine lab:
 The only recommended routine labs include thyroid functions and vitamin B level.
 Other biochemical and hematological lab may be helpful.
4. Imaging:
 CT and MRI brain: detect hydrocephalus, tumor, demyelination, vascular affection, regional atrophy as hippocampal atrophy in AD.
 PET: detect regional deficit in blood flow and metabolism.
 SPECT is helpful in detection of regional deficits.

10. 5. EEG:
 Identify subclinical seizure activity.
 Identify the characteristic changes of spongiform encephalopathies.
 Identify the early slow wave changes in AD.
6. CSF:
 Identify infective and inflammatory causes.
 In ad there is decreased a b 1-42 and increased tau.
 Indicated in suspicion of infection or vasculitis, age less than 55 yrs., rapidly progressive dementia,
hydrocephalus, metastatic carcinoma.
7. Tissue biopsy: muscle (mitochondrial); tonsil (variant CJD); meningeal and cerebral biopsy (isolated
vasculitis).

11. Alzheimer’s Disease (AD)
AD is a progressive disorder of recent
episodic memory, language, visuospatial
function,
and executive function associated with high
frequency of neurobehavioral abnormalities.
Epidemiology
 Age of onset: late onset (above 65) or early
onset disease (40-50 years).
 Affects F > M.

12. Clinical Picture
Patient is unaware of cognitive impairment.
1.Memory impairment:
 Earliest deficit: affecting episodic (remembering by re-experiencing) and
autobiographical memory(memory for our life story eg. Goals & events ),
declarative learning, and may be remote memory. There is somehow preserved
procedural memory and learning.
 Semantic memory is also impaired relatively early, but less prominent.
2. language: early impairment of verbal semantic memory (categories} may be focal
dysphasia, word finding difficulty and affection of verbal fluency.
3. Visuospatial defective (judgment of direction and distance ,visual attention) &
visuoperceptual deficits (impairment of visual object recognition (agnosia) are
prominent & early.
4. Apraxia may occur late (especially ideomotor apraxia}.
5. Anosognosia (neurological condition in which the patient is unware of their
neurological deficit or psychiatric condition), subtle executive function deficit.

13. 6. Neuropsychiatric manifestations include:
a) Mood changes (depression, agitation, or disruptive behavior due to language deficits & direct pathological effect
because of loss of LC neurons).
b) Psychosis (hallucinations usually are visual and occasionally auditory- delusions of theft and paranoia}.
c) Behavioral disturbances (apathy, social disengagement, disinhibition, verbal and physical aggression, wandering,
agitation, uncooperativeness, urinary incontinence, binge eating, catastrophic reaction, attempt of self-inflicting
harm).
7. Generalized seizures or myoclonus in 10%.
8. In late stages: patient is bed ridden, incontinent, impaired. swallowing, unresponsiveness state (vegetative like), and
mute.

14. Pathology
 Generalized cortical atrophy, especially
temporal lobes.
 Deposits of amyloid A4 protein in
cortex with neuritic plaques (which are
spherical microscopic lesion; a core of
extracellular amyloid is surrounded by
enlarged axonal endings).
 Neurofibrillary tangles (which are
fibrillary intracytoplasmic structure
within the neurons) contain tau and
ubiquitin proteins.
 In cases of amyloid angiopathy,
amyloid is found in vessel walls.

15. Neurotransmitter changes
Degeneration of cholinergic neurons in the basal forebrain is the largest change in AD.
Genetics
Familial cases tend to present at a younger age. Familial autosomal dominant cases
associated with mutations in three genes:
 APP gene (amyloid precursor protein)
 Presenilin 1 and 2.
 Apolipoprotein E4.

16. Stages of AD
A) Early: mild forgetfulness, difficult I recall familiar
words. Familiar situations may appear strange
to the patient.
B) Middle: memory and reasoning ability are lost
with arithmetic skill impairment. The patient may
be aggressive and paranoid.
C) Advanced: bowel and bladder control declined.
Inability to recognize others. Gait is impaired.
D) Final stage: inability to think, speak, move, or
understand.

17. Management
1. Multidisciplinary team with nurse, counsellor, psychiatrist.
2. Essential to consider care wellbeing.
3. Mild cognitive impairment: 10–15% risk of progression to AD. No data on treatment with acetylcholinesterase
inhibitors (AChIs).
4. AChI and memantine (NMDA receptor antagonist) may improve cognition at least for 6 months. Patients may derive
benefit for 2–3 years. If no benefit from one drug, switch. Stop if MMSE < 12.
5. Psychotic symptoms—consider (initial doses):
 Quetiapine, 12.5–25 mg od.
 Olanzapine, 2.5 mg od.
 Risperidone, 0.25–0.5 mg daily.
1. Depression common: consider SSRI (e.g., citalopram 10–40 mg daily).
2. Restlessness and agitation: risperidone 0.25 mg or oxazepam 10 mg od–tds.
3. Insomnia: temazepam 10–20 mg or zopiclone 3.75–7.5 mg nocte.
4. Delirium: exclude medical causes (haloperidol 0.5 mg od)

18. Vascular Dementia
 2nd most common dementia of elderly.
Causes and Types
- Brain injury from cerebrovascular disease:
a) Multiple Cortical Infarcts (multiple ischemic lesions in cerebral cortex cumulatively result in loss of enough neurons to produce
dementia  multi-infarct dementia
b) Occlusive Disease of Small Penetrating Cerebral Arterioles [Microangiopathy] → MULTIPLE BILATERAL LACUNAR INFARCTS
(small infarctions in deep hemispheric white matter) (Binswanger disease, s. subcortical arteriosclerotic encephalopathy)
c) Strategically Placed Single Infarct (may cause specific cognitive deficit, aphasia, amnesia, but rarely causes dementia)
d) Cerebral Hypoperfusion (chronic, reversible) - most experts reject such mechanism.
e) Amyloid Angiopathy (not associated with dementia but predisposes older persons to hemorrhagic lobar stroke).
Pathology
Multiple remote cystic infarcts in various locations over several years

19. Clinical Features
Clinical features vary, but few generalizations are applicable (when compared with Alzheimer's disease):
1) Men > women
2) Often have risk factors (hypertension, diabetes, hyperlipidemia, cigarette smoking).
3) History of transient ischemic attacks
4) Earlier age of onset (< 75 yrs.)
5) Onset may be abrupt.
6) Stepwise deterioration!!! (Episodes of sudden neurologic deterioration)
7) Focal neurologic signs (limb rigidity, spasticity, hyperreflexia, extensor plantar responses, gait disturbance)
8) Pseudobulbar palsy (emotional lability, dysarthria, dysphagia).
9) Memory disturbance is of RETRIEVAL type - able to register information but difficulty spontaneously recalling it -
categorical clues or multiple choices help.
10) Shorter survival (after mental status changes onset).

20. Clinical Subtypes
Cortical Syndrome (multi-infarct dementia): abrupt onset of cognitive failure, focal sensorimotor signs, severe
aphasia (when present).
Subcortical syndrome (Binswanger disease):
1. Dementia of subtle onset and slow progression (vs. multi-infarct dementia)
2. Bilateral pyramidal signs (lateralizing motor signs are uncommon).
3. Gait imbalance (with marche a petit pas)
4. "frontal" abulic behavior, mildly impaired memory.
5. Pseudobulbar signs, urinary incontinence.
6. Associated (but not always) with severe hypertension and systemic vascular disease.

21. Multiple areas of abnormal high signal
intensity in periventricular white matter,
corona radiata and lentiform nuclei
(arrows).

22. Diagnosis
- BRAIN IMAGING (provides supporting, but not diagnostic, evidence):
a) focal infarctions in strategic cortical locations.
b)Binswanger disease - ischemic periventricular white matter changes, sparing cortex,
and basal nuclei.

23. Treatment
By stroke prevention strategies:
1) Antihypertensives
2) Cigarette cessation
3) Blood cholesterol reduction
4) Anticoagulants / antiplatelet therapy (ASPIRIN, CLOPIDOGREL, TICLOPIDINE).

24. Thank you
Mohamedrizk.med@o6u.edu.eg