Alzheimer disease

Question 1

Fisiopatologia (la beta amiloide è nella sostanza grigia)

Answer 1

1.Extracellular senile plaques (neuritic plaques) in the grey matter of the brain
Aβ protein is the main component of the plaques.
Enzymatic cleavage of transmembranous APP by β-secretase and γ-secretase → Aβ peptide aggregation → formation of insoluble plaques together with tau protein and microglia → neurotoxic effect

2.Intracellular neurofibrillary tangles
Tangles are composed of hyperphosphorylated tau protein(a microtubule-associated protein).
Increased phosphorylation (hyperphosphorylation) of tau → formation of intracellular fibrils → neurotoxic effect

3.Overall reduction of cholinergic function

Question 2

Fattori genetici

Answer 2

1.Amyloid precursor protein (APP) gene
APP. Linked to 10–15% of early-onset familial AD cases.Patients with trisomy 21 have an increased risk of early-onset AD because of APP overexpression (the APP gene is located on chromosome 21).

2. Presenilina 1 : Linked to ∼ 50% of familial AD cases. Earlier onset compared to AD due to mutations of other genes (median is ∼ 43 years)
3. Presenilina 2:Mutations cause the rarest form of familial AD.

4.Risk of late-onset AD increases with the number of carried Apo ε4 alleles.
Apo ε2 alleles may have a protective effect. Apo ε3 alleles neither decrease nor increase risk of developing AD

Question 3

Clinica (la perdita della memoria a breve termine è il sintomo più comune)

Answer 3

1. Short-term memory impairment (insidious onset, slow progress with episodic memory affected first)
2. Language impairment (tipico all’esordio nella demenza fronto temporale)
3. Temporal and spatial disorientation (patients are usually not oriented to person, place, time, or events)
4. Impairment of executive functions and judgment

Question 4

Sintomi non cognitivi

Answer 4

• Behavioral changes
• Apathy
• Aggression, irritability, and agitation
• Mood disorders (e.g., symptoms of depression)
• Anxiety and mutism
• -Hallucinations and paranoia
• Hyposmia
• Insomnia
• Urinary incontinence
• Myoclonus
• Seizures (tipiche delle fasi tardive)

Question 5

Percorso diagnostico

Answer 5

-Mini-Mental State Examination, Montreal Cognitive Assessment

• Rule out reversible causes of dementia.
  1. Review medications.

2. Laboratory tests (rule out hypothyroidism and vitamin B12 deficiency)
3. Neuroimaging (rule out vascular dementia, hydrocephalus, tumors)
4. Clinical assessment for depression to rule out pseudodementia: See diagnostic criteria for major depressive disorder.(la pseudodemenza migliora con la privazione di sonno a differenza della demenza)
5. AD can only be definitively diagnosed with neurohistopathological examination, which is only conducted post mortem.

Question 6

Diagnosi

Answer 6

Synopsis of diagnostic criteria

1.Insidious onset (symptoms are often first noticed by the patient’s relatives)

2.Objectively confirmed progressive loss of function in at least two cognitive domains (usually including memory impairment)
Impaired activities of daily living (e.g., difficulties at the workplace)

3.No other plausible explanation (e.g., delirium)

4. Cerebrospinal fluid
   - Increased phospho-tau protein
   - Decreased β-amyloid proteins Aβ1-42

5.CT/MRI
Signs of generalized or focal cerebral atrophy: enlarged ventricles (ventriculomegaly), narrowing of gyri, and prominent cerebral sulci (hydrocephalus ex vacuo)
Disproportionate atrophy of the hippocampus and/or medial temporal lobe

6.EEG: slower basic rhythm
Evoked potentials: long latency

7.PET
FDG-PET: temporoparietal hypometabolism
Amyloid PET: increased amyloid uptake signal

8.Neuropsychological testing (e.g., MMSE and MoCA): Repeated performance measurement is used to track disease progression.

Question 7

Meccanismo patologico

Answer 7

1.Cerebral atrophy
Damage to the hippocampus and parahippocampal cortex (medial temporal lobe structures) is the earliest gross pathological change.
-Axonal degeneration
-Neuronal loss

2-Degeneration of cholinergic neurons in the nucleus basalis of Meynert

3.Diffuse cortical atrophy occurs as the disease progresses.

4. Amyloid beta (Aβ): stains with Congo red under polarization
   - Cerebral amyloid angiopathy
   - Extracellular senile plaques
5. Tau protein
   - Intracellular neurofibrillary tangles
   - Stain with Gallyas silver.

Question 8

Complicanze

Answer 8

1. Infections: Aspiration pneumonia is the most common contributing factor to AD-related mortality.
2. Malnourishment/dehydration
3. Cerebral amyloid angiopathy increases the risk of intracerebral hemorrhage.

Question 9

SCENARIO Uomo di 65 anni con decadimento cognitivo. DOMANDA Quale di questi punteggi Minimental (1-30) corrisponde ad un decadimento cognitivo moderato?

	25
	30
	26
	9
	✔19

Answer 9

Il Minimental è un test molto usato nelle valutazioni cognitive, sotto 26 lieve deficit, sotto 21 deficit moderato, sotto 10 deficit grave