DEFINITION
Alzheimer's disease is the most common form of degenerative dementia.
It is defined as a degenerative process that progressively affects brain cells and therefore brain function,
gradually making the individual who is affected incapable of performing a normal life and eventually causing death due to causes related to the clinical state.
EPIDEMIOLOGY
Epidemiologically except in rare genetic "early-onset" forms (with juvenile onset),
the factor most closely related to the incidence of the disease is age.
Very rare under the age of 65,
its incidence increases steadily with age,
reaching a significant spread in the population over 85y.o..
SYMPTOMS
The earliest observable symptoms are often mistakenly considered problematic "age-related" or manifestations of stress.
In the early stages,
the most common symptom is the inability to acquire new memories and difficulty in recalling recently observed events.
With the advance of the disease,
the clinical condition may include confusion,
irritability and aggression,
mood swings,
language difficulties,
long-term memory loss and progressive sensory dysfunction.
PATHOLOGY: BETA AMYLOID
In healthy subjects the APP (Amyloid Precursor Protein),
through a reaction catalysed by alfa-secretase,
produces the peptide p3.
In diseased subjects the enzyme that intervenes on the App is not the alpha-secretase but its variant beta-secretase,
leading to the production of a peptide of 40-42 amino acids: the beta-amyloid.
Beta-amyloid does not have the biological characteristics of the natural form,
but tends to deposit itself in extracellular aggregates on the neurons membrane forming plaques.
These neuronal plaques trigger an inflammatory process that activates an immune response by invoking macrophages and neutrophils,
which produce cytokines,
interleukins and TNF-alpha thereby irreversibly damaging the neurons.
TAU PROTEIN
Further studies reveal an additional pathological mechanism:protein Tau,
that is abnormally phosphorylated,
accumulates inside neurons in so-called "neurofibrillary aggregates”.
CHOLINERGIC NEURONS
Particularly affected by this disease process are cholinergic neurons,
especially those of the cortical-subcortical areas ,expecially in the hippocampuss.
It follows deficiency of acetylcholine.
MILD COGNITIVE IMPAIRMENT - ALZHEIMER DISEASE
MCI is a widely used term for cognitive problems that do not fulfill criteria for dementia.
It is generally used to refer to a transitional phase between normal cognitive function a probably Alzheimer disease.
Episodic memory is the most commonly affected domain,
expecially the capacity to retain new information.
(AJNR Am J Neurorad 32:60 - 66,
Jan 2011).
The idea that AD is preceded by a long period of subtle cognitive decline called MCI has been extensively discussed in the literature since its conceptualization in the early 1990's.
DIFFERENTIAL DIAGNOSIS
•SENILE DEMENTIA ALZHEIMER TYPE - SDAT
Cortical temporal atrophy - increase in ventricular and sulcus size.
•FRONTOTEMPORAL DEMENTIA
Atrophy in frontal and temporal cortex. DD with AD and SDAT is difficult also for overapping of symptoms.
•VASCULAR DEMENTIA
Ischemic disease is widely distributed.
Differential diagnosis is easy thanks to history,
pathognomic characteristic of imaging and contribution of magnetic resonance.
•DEMENTIA WITH LEWY BODIES
•CREUZFELDT JACOB’S DISEASE
•TUMORS – HIDROCEPHALUS – SUBDURAL EMATOMA OTHERS