Dementia
Dementia
Dementia
Yamaan wael
Sharaf Al-Karaki
Mahmoud hmidan
GENERALLY , WHAT IS IT ?
Feeling overwhelmed 2
THE CAUSES OF DEMENTIA :
3
D→Diabetes
E→Ethanol
M→Medication
T→Trauma
I→Infection
A→Alzheimer
▪ Memory loss, difficulty retaining new information
▪ Language impairment
▪ Executive dysfunction
▪ Behavioral disturbance
▪ Personality change
DIAGNOSIS
→DIAGNOSTIC IMAGING
CT scan
▪ Reveals microinfarcts indicative of
vascular
dementia
OTHER DIAGNOSTICS
▪ Mental status examination
▫ Identify cognitive impairment with standardized
mental status scales
▪Neuropsychological testing ▫
DEMENTIA CT
ALZHEIMER’S DISEASE :
AD IS THE MOST COMMON CAUSE OF
DEMENTIA IN ALL AGE GROUPS,
OCCURRING WITH MARKEDLY INCREASED
FREQUENCY IN THE ELDERLY. IT IS A
NEURODEGENERATIVE DISORDER
CHARACTERIZED PATHOLOGICALLY BY
INTRACELLULAR NEUROFIBRILLARY
TANGLES COMPOSED OF ‘PAIRED HELICAL
FILAMENTS’, AND EXTRACELLULAR
NEURITIC PLAQUES CONTAINING AN
AMYLOID CORE, ALONG WITH NEURONAL
LOSS
- ▪ NEURODEGENERATIVE DISEASE; BETA AMYLOID PLAQUE, NEUROFIBRILLARY
TANGLE FORMATION → IMPAIRED NEURONAL SIGNALING, NEURON APOPTOSIS
▪ MOST COMMON FORM OF DEMENTIA
▪ SPORADIC (95% OF CASES), TYPICALLY > 60 YEARS OLD
▫ EARLY AD ONSET UNUSUAL, MOSTLY FAMILIAL
▪ AMYLOID PRECURSOR
PROTEIN (APP)
▪ Debilitation →
dehydration,
▪ Complete debilitation,
dependence on others malnutrition, infection ▪
Death occurs 5–10 years
after symptoms onset
MNEMONIC : RONALD , FEATURE OF AD
R→Reduction of Ach
O→Old age
N→Neurofibrillary tangles
L→Language impairment
NO CURE
MEDICATIONS →
▪ Acetylcholinesterase inhibitors
▪ Vitamin E supplementation may provide
benefit
▪ Memantine (advanced stages)
FRONTO-TEMPORAL DEMENTIA
(Pick ‘s disease) Is another major category of disease that results in dementia,
some of these dementias are caused by mutations in the gene encoding tau,
the protein found in tangles ( pick bodies). 3R isoform hyperphosphorylation
leading to the unattachment of tau proteins from the microtubule then the
protein accumulates as tangles inside the nerve leading to damage and
eventually apoptosis
PRESENTATION
Pick’s dementia patients share clinical features (progressive language deterioration &
personality changes) corresponding to degeneration & atrophy of temporal& frontal lobes.
These symptoms often occur before memory disturbance, & this difference in presentation can
assist in their separation from cases of AD on clinical grounds.
►GROSSLY, the basic finding is frontal & temporal lobes atrophy. Different subgroups characterized by
specific inclusions, which in some consist of abnormal accumulations of tau.
NON-DEGENERATIVE CAUSES
OF DEMENTIA
VASCULAR DEMENTIA
PATHOPHYSIOLOGY
.Vascular dementia is caused by reduced blood flow to the brain → ↓ brain blood supply → death of brain cells → stepwise
cognitive function decline, gait abnormality, focal neurological deficits
▪ Second most common dementia cause in elderly
▪ High Alzheimer disease comorbidity
This can happen as a result of:
•narrowing and blockage of the small blood vessels inside the brain
•a single stroke, where the blood supply to part of the brain is suddenly cut off
•lots of "mini strokes" (also called transient ischaemic attacks, or TIAs) that cause tiny but widespread damage to the brain
In many cases, these problems are linked to underlying conditions, such as high blood pressure and diabetes, and lifestyle
factors, such as smoking and being overweight.
▫ Late-onset memory impairment Binswanger’s disease ------ Large subcortical white matter areas involved
CAUSES OF VASCULAR DEMENTIA
4. ▪ Vasculitis
SIGNS & SYMPTOMS ( CORTICAL AREA DEPENDENT )
The abnormal form of this protein can act as an infectious agent, since it propagates itself & injures the cells in which it is present.
Most cases of prion disease are either sporadic or associated with mutations in the gene that encodes PrPc.
The unique pathogenesis of prion diseases is related to changes in the conformation of PrP from its native PrPc form to an
abnormal configuration called either PrPsc (for scrapie) or PrPres (for Protease resistant) (F23-20).
In the abnormal conformation, the prion protein becomes resistant to protease digestion. Once formed, PrPsc can then initiate
comparable transformation of other PrPc molecules.
The infectious nature of PrPsc protein comes from this ability to propagate the pathologic conformational change. The
conformational change can occur:
(I) spontaneously at an extremely low rate & accounts for sporadic cases of prion disease (1per million person).
(II) (II) If there is a mutation in the gene encoding PrPc, then the change can occur at a higher rate; this results in familial forms of
prion disease.
Accumulation of PrPsc in neural tissue seems to be the cause of cell injury, but how this material leads to the development of
cytoplasmic vacuoles & eventual neuronal death is still unknown!
❖Creutzfeldt-Jakob Disease (CJD)
• CJD is a rare but well-characterized prion disease that manifests clinically as a rapidly progressive dementia.
• It is sporadic in about 85% of cases, with a worldwide annual incidence of about 1 per million; familial forms also exist. The disease has a peak incidence in the 7th
decade.
There are well-established cases of iatrogenic transmission by deep implantation electrodes & contaminated preparations of human growth hormone (GH)
Presentation begins with mild changes in memory & behavior that rapidly progress to dementia. The disease is uniformly fatal, with an average duration of only 7
months.
H, the pathognomonic finding is a spongiform transformation of the cerebral cortex & deep gray matter structures (caudate, putamen); this consists of a multifocal
process that results in the uneven formation of small, empty, microscopic vacuoles of varying sizes within the cerebral substance(“ neuropil” 4.17) & sometimes in the
perikaryon of neurons (F23-21A).
F 23-21: Prion disease. A, Histology of CJD showing spongiform 4.17: Creutzfeldt-Jakob disease: Brain. The main features are loss of neurons, demyelination &
change in the cerebral cortex. Inset, High magnification of neuron with spongiform change (confluent vacuolation {thin arrow} of the cerebral white matter “neuropil”).
vacuoles. However there is no inflammatory reaction!
• In advanced cases, there is severe neuronal loss, reactive gliosis, & sometimes expansion of the vacuolated areas into cystlike
spaces ("status spongiosus").
No inflammatory infiltrate is present !
▼In all forms of prion disease, immunohistochemical staining demonstrates the presence of proteinase K-resistant PrPsc in
tissue ( 4.16).
▼Western blotting of tissue extracts after partial protease digestion allows detection of diagnostic PrPsc.