Dementias Flashcards
What is Creutzfeldt-Jacob disease?
It is a rapidly progressive neurodegenerative condition associated with brain shrinkage and deterioration. Disease course is more rapid in comparison with the one of Alzheimer’s disease. A brain section these patients will show spongiform pathology.
Etiology —> it is a prion disease caused by the deposition of pathological protein in this case PrP.
Forms —> sporadic 90% of cases no mutations, genetic 10% of cases mutations in PrP gene, iatrogenic associated with brain graft implantation very rare, variant mucca pazza associated with the consumption of products derived by cows suffering from bovine encephalopathy.
Diagnosis —> EEG will show periodic share wave complexes, CSF analysis will show alterations such as total tau and non phosphorylated tau, imaging with DWI and FLAIR shows hyper intense lesions along cortices and caudate and putamen hyper intensity. Cognitive impairment should always be present in order to diagnosis CJD.
It is a rapid disease course as the average survival time is 6 months, cognitive impairment is rarely the only issue of this disease. In a few months patients develop myoclonus, impairment of visual and cerebellar pathways, and other signs.
No treatment.
What are alpha synucleinopathies?
α-SYNUCLEINOPATHIES are neurodegenerative conditions associated with α-Synuclein protein’s alteration/deposition. Parkinson’s disease is the most frequent one, then there are also Dementia with Lewy bodies and Multiple System Atrophy (MSA).
What is dementia with lewy bodies? Epidemiology and pathological hallmarks?
DLB is a common yet underdiagnosed type of dementia as it has a similar onset age of AD. It can be considered as a mix between Parkinson’s and AD as it is characterized by both cognitive and motor impairment
Epidemiology —> some epidemiological studies suggest it is a rare diseased others claim that 23% of AD patients are actually DLB patients.
Pathological hallmarks —> alpha synuclein neuronal inclusions accompanied by neuronal loss. It is common to observe AD pathology in these patients such as amyloidosis and P-TAU protein.
Diagnostic criteria of DLB?
To diagnose : Essential criteria is the presence of dementia, followed by the presence of core clinical features, such as fluctuating cognition, hallucinations, REM sleep disorder and parkinsonisms.
To better differentiate AD from DBL after the MMSE the patients can be asked to perform the MMSE pentagon copy test. AD patients manage to copy the origin picture but DLB patients even with mild cognitive impairment aren’t able to do so
Differences between DLB, Parkinson’s and AD?
Main pathology
AD : B amyloid and TAU
PD : lewy bodies in brain stem
DLB : Lewy bodies in cortex and Brainstem
First symptoms
AD : episodic memory loss
PD : motor symptoms
DLB : cognitive impairment
Core clinical features of DLB? Supportive clinical features?
- Fluctuating cognition/level of consciousness —> usually a late clinical features but can also happen early in disease course. Caregivers report alternated levels of consciousness during the day due to frontal lobe involvement. Patients tend to be lethargic, drowsy and stare into space.
- Visual hallucinations —> very typical of DLB and occur very early in the disease course. These are due to occipital lobe involvement. Here the patient is aware the hallucinations are not real, the patient can criticize and report these hallucinations. They are usually very well formed and detailed.
- REM sleep disorder —> patients may develop this 2 to 6 years before disease onset. It is common both in DLB and Parkinson’s.
Supportive clinical features include severe autonomic dysfunction such as postural instability, syncope, consitpation, urinary incontinece.
Indicative biomarkers and specific exams used to aid diagnosis?
- Reduced dopamine transported uptake in basal ganglia demonstrated by SPECT or PET.
- Abnormal (low uptake) iodine MIBG myocardial scintigraphy.
- Polysomnographic confirmation of REM sleep without atonia.
DaTSCAN is highly specific for alpha synucleinopathies as it looks for reduced dopamine transported uptake. It cannot distinguish DLB from Parkinson as they display similar conditions.
Myocardial scintigraphy can be used to assess the presence of postganglionic sympathetic cardiac innervation due to alpha synuclein deposition.
FDG PET scan is used to assess the metabolic rate within the cortex, it is used in the DDX between DLB and AD bc the involved cortical regions differ (at least in the early stages). In AD hypo metabolism is present in temporal/parietal regions with occipital spared. In DLB occipital is involved.
Cingulate island sign signals the normal metabolism in the posterior cingulate cortex and reduced metabolism in the adjacent occipital cortex, it is an indicator for DLB.
What is vascular cognitive impairment?
It is a very common type of irreversible dementia. 17% of patients with cognitive impairment have vascular dementia as an etiology and in 10% of cases it can also be associated to other neurodegenerative conditions like AD.
VD progression is step wise and is due to the accumulation of vascular lesions.
Patient features include risk factors for acute cerebrovascular disorders that can be associated to cognitive impairment.
Cognitive impairment characteristic are variable as it depends on the involved region. Since the frontal lobe is the largest region it is also the most frequently involved. Mean features include executive function and attention deficits.
Diagnosis is strengthened by history of stroke and falls, focal neurological signs, neuroimaging positivity for vascular disorders.
Main cerebrovascular disorders associated to cognitive deterioration are large cortical infarction (first cause of VD), multiple lacunae infarcts and extensive white matter lesions.
What is frontotemporal dementia?
It is a clinical condition characterized by a focal atrophy of the frontal lobe and of the anterior portion of the temporal lobe. The occipital and posterior temporal regions are spared. Opposite pattern of AD.
FTD is an umbrella term as it include many different syndrome such as taupathies and TDP43 pathologies. In between these two we have three syndrome : behavioral variant of FTD, semantic variant of PPA, and nonfluent/agrammatic variant of PPA.
Clinical manifestations? Epidemiology and genetics of FTD?
If the frontal lobe is involved we should expect cognitive deficits but also behavioral changes. A neurodegenerative process at this level will be associated to bizzarre behaviors such as stiff jerky posture, uninhibited socially inappropriate behavior, decreased speech, loss of awareness etc.
Epidemiology —> involves younger patients than AD around 60-65 yr. It is rarer than AD but since the patients are younger the social impact is greater.
Genetics —> main two pathologies associated with FTD are tau and TDP43. The semantic variant is mostly associated with TDP43 pathology, the non fluent variant is more frequently associated to taupathy and the behavioral is more challenging, 50/50 scenario. Most frequent mutated gene is C9ORF72.
Behavioral variant of FTD?
Of course behavioral changes are very important in diagnosing this variant and they include : a change from baseline personality, apathy, loss of sympathy, compulsive and ritualistic behaviors, changes in dietary and oral habits, lack of awareness.
Key cognitive features —> frontal region involvement leads to struggle to articulate words and the portal regions to difficulty to remember words. Executive dysfunction is prominent and can be tested with the modified card sorting test.
Diagnostic process —> it is based on characteristic behavioral and cognitive symptoms. In addition there must be a clear picture of neurodegeneration in frontal and temporal regions by MRI of FDG-PET. Classic finding is knife edge atrophy.
The frontal variant of AD cannot be excluded based on prior information therefore CSF analysis is performed.
Treatment for dementias?
As of today in Italy we don’t have any disease modifying drugs but generally safe symptomatic drugs that stabilize the patient. They include cholinesterase inhibitors and NMDA receptors non competitive antagonists.
Cholinesterase inhibitors include donepezil, rivastigmine, galantamine.
NMDA receptor antagonist include memantine.
