Parkinsons
These are 3 abnormal features of gait in Parkinsons disease.
What are: Shuffling, short-stepped gait Freezing Festination Decreased arm swing En bloc turning Stooped posture Postural instability
These are 3 risk factors that increase the risk of developing dementia.
Non-modifiable risk factors:
1) AGE: incidence of AD doubles every 10 years after age 60
2)Genetics:
- AD young onset Amyloid PP, Presenilin 1 or Presenilin 2 genes
–AD late onset ApoE ε4 allele
3) Mild Cognitive impairment
MODIFIABLE risk factors:
1) Low education level (no secondary school)
2) Head trauma (repetitive mild head injury vs. TBI)
3) Alcohol abuse
4) Hearing loss Hazard ratio 1.24 for cognitive impairment
5) Stroke
6) CVD: obesity, HTN, hyperlipidemia, DM
7) Smoking
8) Social isolation
10) Depression
11) OSA
These are the two most common types of dementia in people over age 65.
What are AD and Vascular?
- Alzheimers' ~50-70%
- Vascular ~20-30%
- DLB ~ 15%
- FTD ~5%
- Parkinsons disease dementia ~5%
- Other ~2%
These are the main criteria for frontotemporal dementia, behavioural variant
What are:
Possible bvFTD requires a combination of 3 of 6 clinical features:
●Disinhibition
●Apathy/inertia
●Loss of sympathy/empathy
●Perseverative/compulsive behaviors
●Hyperorality
●Dysexecutive neuropsychologic profile
Probable FTD: clinical criteria, plus demonstrable functional decline and imaging findings that reflect the principal anatomic location of neurodegeneration in bvFTD (ie, frontal and/or temporal lobe atrophy, hypometabolism, or hypoperfusion).
bvFTD with definite FTLD pathology satisfied when cases of possible or probable bvFTD, accompanied by either biopsy or postmortem histopathologic evidence of FTLD or evidence of a known pathogenic mutation
These are the three types of cholinesterase inhibitors currently available in Canada.
What are: Donepezil Rivastigmine Galantamine
These are the core criteria of DLB.
Core clinical features (The first 3 typically occur early and may persist throughout the course.)
- Fluctuating cognition with pronounced variations in attention and alertness.
- Recurrent visual hallucinations that are typically well formed and detailed.
- REM sleep behavior disorder, which may precede cognitive decline.
- 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
These are pathologic or structural features of Alzheimers Dementia
What are:
- senile neuritic plaque formed around an Aβ core
- neurofibrillary tangle (abnormal tau clumped together)
- cerebral atrophy tends to be diffuse, affecting the frontal, temporal and parietal lobes with particular involvement of the medial temporal structures (hippocampus, parahippocampal gyrus)
- tau protein
Pathologic features of Vascular dementia
- Mild to moderate, often asymmetrical, dilatation of the lateral ventricles
- White matter usually appears irregularly pitted or granular and contains ill defined foci of yellow or grey discoloration.
- Scattered lacunar infarcts almost always present
- Sometimes brain contains 1 or > larger infarcts ( in watershed regions between the perfusion territories of the major cerebral arteries)
- Occasionally, dementia caused by hippocampal sclerosis, with hippocampi looking greyish brown, shrunken, and granular
- Rarely bilateral infarcts involving the hippocampus or thalamus are the cause of dementia.
- Small vessel disease microscopically:
In the deep cerebral white matter and basal ganglia: small arteries and arterioles have thickened, hyaline walls with replacement of smooth muscle by collagen.
Often enlargement of perivascular spaces.
Rarefaction of white matter 2ndary to combination of nerve fibre degeneration, gliosis, and patchy demyelination.
Microinfarcts in the cerebral cortex.
Other abnormalities:
These can include foci of old haemorrhage (with clusters of haemosiderin laden macrophages), cerebral amyloid angiopathy (sometimes severe), and hippocampal sclerosis.
These are the three main types of pathologic entities that contribute to Vascular dementia.
What are: 1) Large artery infarctions - usually cortical, sometimes also or exclusively subcortical in location.
2) Small artery infarctions or lacunes, - exclusively subcortical, in the distribution of small penetrating arteries, affecting the basal ganglia, caudate, thalamus, and internal capsule, cerebellum and brainstem
3) Chronic subcortical ischemia occurring in the distribution of small arteries in the periventricular white matter
These are the three classic features of NPH.
What are:
1) Gait difficulty (magnetic, apraxic, or frontal)
2) Cognitive disturbance ( subcortical and frontal features: psychomotor slowing, decreased attention and concentration, and apathy)
3) Urinary incontinence (urgency at early stages) Other features:
- Lower extremity spasticity, hyperreflexia, and extensor plantar responses
- Decreased coordination, hand tremor (usually postural rather than resting), and bradykinesia suggestive of Parkinsonism
- Rigidity that is usually characterized by paratonia or Gegenhalten rather than the cogwheel rigidity of parkinsonism.
- In late stages, frontal release signs, akinetic mutism, and quadriparesis may occur
These are contraindications to prescription of memantine.
Hypersensitivity to any component of formulation CrCl <15 avoid; Caution in seizure disorder: lowers seizure threshold
These are 4 distinguishing features between Idiopathic parkinsons and DLB.
1. Temporal course (dementia precedes or within 1 yrs of parkinsonisms in DLB)
- DLB should be diagnosed when dementia occurs before or concurrently with parkinsonism. Term Parkinson disease dementia (PDD) should be used to describe dementia that occurs in the context of well-established Parkinson disease.
2. Older age of onset in DLB
3. Decreased levodopa responsivity in DLB
4. Faster clinical decline in DLB
5. Pathology in DLB is cortical LB, while in PD is subcortical LB + loss of pigmented dopaminergic neurons in the substantia nigra
These are the main criteria for MCI.
What are:
1. change in cognition recognized by the affected individual or observers;
2. objective impairment in 1 or more cognitive domains;
3. independence in functional activities; and
4. absence of dementia
Main criteria for MBI:
Affective dysregulation (e.g. anxiety, dysphoria, changeability, euphoria, irritability)
Impulse dyscontrol (e.g. agitation, disinhibition, gambling, obsessiveness, behavioral perseveration, stimulus bind)
Social inappropriateness (e.g. lack of empathy, loss of insight, loss of social graces or tact, rigidity, exaggeration of previous personality traits)
Abnormal perception or thought content (e.g. delusions, hallucinations)
Behaviors are of sufficient severity to produce at least minimal impairment in at least one of the following areas:
Interpersonal relationships
Other aspects of social functioning
Ability to perform in the workplace
- patient should generally maintain his/her independence of function in daily life, with minimal aids or assistance
- not attributable to another current psychiatric dx or dementia syndrome
This is the approximate percentage of patients with MCI that develop dementia per year.
~10-15%
These are 2 features of HIV associated dementia.
What are:
1) substantial memory deficits
2) negative personality and mood changes
3) impaired executive functioning, poor attention and concentration
4) mental slowing, and apathy
**absence of higher cortical dysfunction including aphasia, agnosia, and apraxia help distinguish HAND from classical "cortical" dementia
These are three contraindications to the use of cholinesterase inhibitors.
What are:
1) hypersensitivity to the drug or any component of the formulation
2) seizure disorder
3) cardiac conduction abnormalities, particularly heart block
4) uncontrolled obstructive lung disease
5) active peptic ulcer disease
6) symptomatic bradycardia
7) unexplained syncope
Attention, visuospatial and executive dysfunction
What are the main cognitive domains impaired in DLB?
This is the most common domain of cognition which is impaired in the presentation of Alzheimers Dementia.
Learning and recall.
These are the two screening tools that have the highest sensitivity and specificity for diagnosis of dementia.
What are the BNA, MOCA?
- MOCA sens 100% (MCI 90%), spec 87%
- BNA (short form) sens 93% spec 93%
- MMSE sens 79-99%, spec 87-99%, lacks utility for MCI
- RUDAS sens 89, spec 98
- clock drawing sens 20-60%, spec 60-93% CMAJ 2008
What are two negative prognostic indicators for NPH patients:
What are:
1) Early appearance of dementia
2) Moderate to severe dementia, Dementia present for more than two years
3) Gait disorder absent or appearing after dementia
4) Alcoholism
5) MRI findings: Marked white matter disease, Diffuse sulcal enlargement, Medial temporal atrophy
Positive prognostic indicators:
1) Early appearance of gait disorder
2) Gait disorder most prominent symptom
3) Shorter duration of symptoms (<6 months)
4) Positive findings on diagnostic tests: High resistance on CSF infusion test, Clinical response to CSF removal (Tap test, Lumbar drain), B-waves comprising >50 percent of tracing on continuous ICP monitoring
These are 3 neuropsychiatric domains which showed improvement in the Mckeith (Lancet 2000) trial looking at Rivastigmine in DLB.
What are:
1) delusions
2) visual hallucinations
3) anxiety, apathy and attention
Lancet A multicenter study randomly assigned 120 patients with DLB to rivastigmine (6 to 12 mg per day) or placebo for 20 weeks. Patients on rivastigmine showed significantly reduced anxiety, delusions, and hallucinations, and had significantly better performance on a computerized battery of neuropsychological tests, especially tasks requiring sustained attention. The differences between rivastigmine and placebo disappeared after drug discontinuation.
This is usually the first oculomotor abnormality noted in progressive supra nuclear palsy.
What is slowing of vertical saccades.
- Vertical (upward or downward gaze) supranuclear palsy and prominent postural instability with falls in the first year of disease onset
Other criteria (NINDS-SPSP):
- Onset at age 40 or later
- No evidence of other disease that could explain the foregoing features, as indicated by mandatory exclusion criteria
SUPPORTIVE FEATURES: -Symmetric akinesia or rigidity, proximal more than distal
-Abnormal neck posture, especially retrocollis -Poor or absent response of parkinsonism to levodopa therapy
-Early dysphagia and dysarthria
-Early onset of cognitive impairment including at least two of the following:
•Apathy •Impairment in abstract thought •Decreased verbal fluency •Utilization or imitation behaviour (unintentional, unconscious actions triggered by the immediate environment e.g. grasping nearby object) •Frontal release signs
These are three vitamins involved in the homocysteine pathway:
What are: •B6 •B12 •folate
- Homocysteine is neurotoxic in AD:
- neurotoxicity induced by activation of NMDA receptors --> promotion of apoptosis ---> vascular injury from promotion of atherogenesis and proliferation of smooth muscle cells, platelet activation ---> increased burden of ischemic strokes and white matter lesions
This is the percentage of patients with ALS or motor neuron disease that develop dementia.
- Some studies suggest that as many as 30-50 percent of ALS/motor neuron dz patients have or develop FTD (bv)
- incidence of subsequent motor neuron dz in patients who present initially with FTD less known - In patients with motor neuron dz and FTD, the motor presentation is usually that of progressive muscular atrophy with flaccidity and fasciculations affecting the bulbar muscles and upper extremities primarily
--Upper motor neuron signs may be less prominent
This is a type of dementia in which 14-3-3 CSF assay and myoclonus are important in diagnosis.
What is Creutzfeld Jakob disease.
The Centers for Disease Control and Prevention (CDC) outline the following criteria for probable sporadic CJD:
A. Progressive dementia and
B. At least two out of the following four clinical features:
- myoclonus;
- visual or cerebellar disturbance
- pyramidal/extrapyramidal dysfunction
- akinetic mutism
C. One or both of:
- Atypical electroencephalogram (EEG) during an illness of any duration, and/or a positive 14-3-3 (rapid progression) CSF assay with a clinical duration to death less than two years
and/or
MRI high signal abnormalities in caudate nucleus and/or putamen on diffusion-weighted imaging or fluid attenuated inversion recovery (FLAIR) and
D. Routine investigations should not suggest an alternative diagnosis **However, a definitive diagnosis requires these features in combination with specific neuropathologic findings:
These are two structured cognitive tests that have relatively high sensitivity and specificity and include executive function testing domains.
MOCA
Behavioural Neurologic Assessment