Degenerative Diseases Flashcards
T or F: The proportion of change of Alzheimer pathologic change decreases continuously from age 70 to age 100
T
What percentage of AD patients have a dominant inheritance pattern?
<1%
High degree of penetrance
What is the Ribot law of memory?
The remote memories are preserved while the recent ones are lost
T or F in the late stages of AD the patient is left in a state of paraplegia in extension
F. In flexion.
What % of patients in the late stages of AD develop seizures?
5
What are the five main symptomatologies un AD?
Which one is the most prominent?
Amnesia-- MOST PROMINENT Naming Paranoia and personality changes Executive function Visuospatial orientation
Microscopically early in the disease loss of nerve cells is seen where?
What lobes are usually involved in Alzheimer’s disease?
Layer 2 of the entorhinal cortex
Frontal, temporal and parietal–
Most affected: hippocampus, parahippocampus and subiculum
What are the 3 pathological hallmarks of AD?
- Neurofibrillary tangles (hyperphosphorylated form of the microtubular protein tau)
- Amyloid spherical deposits seen with PAS stating (neuritic plaques)
- Granulovacuolar degeneration of neurons in the pyramidal layer of the hippocampus
What particular part of the hippocampus is affected in AD?
What do astrocytes look like in AD?
CA1 and CA2 (of Lorente de No)
Compensatory hypertrophy is seen most in layer 3 and 4
What is tau composed of? what does it form?
beta 2 transferrin –> tau –> tangles
Tau is a discrete cytoskeleltal protein that promotes assembly of the microtubules and stabilizes their structure
What sequence of events favor amyloid toxicity?
Amyloid precursor protein (APP)–> cleaved by beta then by gamma –> Abeta 40 (non toxic) AND Abeta42 (toxic) protein favors fibrillogenesis; amyloid aggregation–> neuronal toxicity
Non toxic route is cleavage by alpha secretase cleavage followed by gamma cleavage
The cholinergic synthetic capacity of demented brains is decreased on account of reduction in cells in?
Basal forebrain nuclei or nucleus basalis of Meynert
What chromosome is the errant amyloid precursor protein seen? How about mutated presenellin genes?
Chromosome 21
Chromosome 14 and 1
T or F. Apo E a regulator of lipid metabolism in its E4 isoform doubles the risk of developing SPORADIC AD.
F. triples the risk!
having 2 e4 alleles guarantees the development of AD if the individual lives until 80
e4 actas a SUSCEPTIBILITY RISK FACTOR– it accelerates the appearance of AD by about 5 years
What 3 genes are responsible for early AD?
APP, PS1, PS2
What is the EEG and CSF in AD?
Late in the disease diffuse slowing on EEG
Occasionally elevated protein
Which areas exhibit diminished activity with SPECT (blood flow) and PET (metabolism) in AD?
- Medial temporal lobes
2. Parietal association regions
T or F the ratio of A beta 42 to tau is IN THE CSF is LOW in AD
What areas in neuropsychologic testing do patients with AD score low in?
T
Memory and verbal access skills
What is the CNS disorder usually seen in the context of alcoholism and malnutrition. The condition classically involves the corpus callosum with necrosis and demyelination.
What are the 3 types of FTLD?
Marchiafava-Bignami disease
- Behavioural variant (frontal lobe involvement)
- The language variant (left frontal or temporal lobe involvement) presenting with apraxia and aphasia
- Posterior cortical atrophy: Progressive loss of the ability to understand and use visual information with relative sparing of memory
T or F. Amyloid plaques and tangle deposition are far more common in the brains of patients with PD 20-30% than in AD
In FTD what are argyrophilic cytoplasmic inclusions called? Diffusely staining ballooned cells?
T
Pick bodies
Pick cells
What percentage of Primary Progressive Aphasias (FTD variant) have Pick bodies? Have AD histopath?
40-40
60% HAVE NO CHARACTERISTIC PATHOLOGIC CHANGE
What are the two types of primary progressive aphasia (a variant of FTLD)?
What are the main components of lewy bodies?
Progressive nonfluent aphasia: Characterized by decreased verbal output and difficulty finding words but the language system is intact
Semantic dementia: The patient retains fluency. Initial sxs characterized by difficulty naming and generating a list of words.
Logopenic aphasia
ubiquitin and synuclein
What is the essential criteria for DLB diagnosis?
What are the 4 core clinical criteria for DLB?
What are the indicative biomarkers?
CRITERIA:
Probable DLB can be diagnosed if:
a. Two or more core clinical features of DLB are present, with or without the presence of
INDICATIVE biomarkers, or
b. Only one core clinical feature is present, but with one or more indicative biomarkers.
Probable DLB should not be diagnosed on the basis of biomarkers alone.
Supportive biomarkers include: Generalized low uptake on SPECT/PET perfusion/metabolism scan with reduced occipital
activity 6 the cingulate island sign on FDG-PET imaging.
ESSENTIAL CRITERIA: Progressive cognitive decline sufficient magnitude to interfere with normal social and occupational function
CLINICAL
1. Fluctuating cognition with pronounced variations in attention and alertness.
2. Recurrent visual hallucinations that are typically well formed and detailed.
3. REM sleep behavior disorder, which may precede cognitive decline.
4. One or more spontaneous cardinal features of parkinsonism: these are bradykinesia (defined as
slowness of movement and decrement in amplitude or speed), rest tremor, or rigidity.
BIOMARKERS
- Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET.
- Abnormal (low uptake) 123iodine-MIBG myocardial scintigraphy.
- Polysomnographic confirmation of REM sleep without atonia.
What drug reduces delusions, hallucinations and anxiety for lewy body dementia?
Rivastigmine