Neurodegenerative disease Flashcards
In broad terms, what is Dementia?
-Describes cognitive, memory, communication impairments associated with Neurodegenerative Disease.
How are Dementias diagnosed?
-Memory / Language / Math / Mental Function tests
-Lab Tests (due to Vit. deficiencies, hormones???)
-Brain Scans (PET, MRI, CT)
-Psychiatric (to rule out depression, other disorders)
When does Alzheimer’s Disease develop?
Mid-Late Adulthood (usually > 65yrs)
T or F: Women are at higher risk of suffering from Alzheimer’s Disease.
True!
What are some factors that increase risk of getting Alzheimer’s?
-Age
-Family History
-Genetic Predisposition (2 APOe-4 genes = Higher risk)
-Previous Stroke
-Depressive
-Diabetic
-Metal Exposure (ie. Arsenic, Lead, Copper, Mercury)
-Smoke / Pesticide Exposure
Alzheimer’s Disease involves atrophy of the cortical parts of the _______ & ______ regions of the brain.
Frontal ; Temporal
In an Alzheimer’s brain, the Gyri ______ & the Sulci ______.
narrow ; widen
The major pathological brain change associated with Alzheimer’s is the development of what?
Neurofibrillary Tangles that contain Amyloid proteins
-This abnormal material induces toxicity, compression & destruction of surrounding brain tissues.
What areas of the brain are particularly susceptible to the effects of Neurofibrillary Tangles?
-Hippocampus (new memory formation)
-Frontal Lobe (behavior, cognition, judgement)
-Parietal Lobe (language)
How does Alzheimer’s progress?
Early: Recent memory loss, mild coordination problems, mood swings. Need reminders for daily activities.
Middle: Persistent memory loss (including past memories)… Rambled speech, lost in familiar places, sleep disturbances, confusion, slow / rigid / tremored movements. Need reminders & some degree of assistance.
Late: Loss of ability to remember, communicate, process information. Immobile, falls likely, incontinence / swallowing issues, extreme issues with mood (can appear delirious). Round the clock management needed.
What two classes of drugs are approved for Alzheimer’s treatment?
1) Cholinesterase Inhibitors (ie. Donepezil, Rivastigmine, Galantamine)
2) NMDA Receptor Antagonists (ie. Memantine)
How does Memantine work?
-Blocks NMDA receptor, preventing chronic activation from Soluble Beta Amyloid oligomers (less excitotoxicity to neurons).
What roles do the following drugs have as adjunct Alzheimer’s therapies:
Escitalopram
Mirtazapine
Carbamazepine
Levetiracetam
Lithium
Methylphenidate
Escitalopram / Mirtazapine: Antidepressants
Carbamazepine / Levetiracetam: Anticonvulsants
Lithium: Mood Stabilizer
Methylphenidate: Stimulant
Aducanumab & Lecanumab work how? Side effects?
-Target Beta Amyloid (reduce cognitive decline)
Adu: Edema & small brain bleeds (imaging abnormalities).
Lecan: Same as above & infusion related things such as chills, flushing, rash.
How does Gantenerumab work?
-Binds aggregated amyloid & subsequent Fc Gamma Receptor binding of Microglia with the MAB promotes Microglial phagocytosis of Beta Amyloid particles.
What is Pick’s Disease?
-Tau Protein accumulation in swollen neurons, which induces cortical atrophy, gliosis (particularly in Frontal Lobe), & cortical neuron loss.
-Primarily affects Frontal & Temporal Lobes (speech & behavior affected).
What are the primary ages of patients affected by Pick’s Disease?
40-60yrs
Pick’s Disease (ie. Frontotemporal Dementia) manifests clinically how?
-Impulsive speech or behavior
-Loss of empathy & interpersonal skills
-Reduced self-awareness & hygiene
-Sudden & frequent mood changes
-Difficulties with speech & language
-Balance / movement issues
Lewy Bodies (found in Lewy Body Disease) are comprised of clumps of Alpha-Synuclein & _________ proteins in neurons.
Ubiquitin
Which brain regions are affected by Lewy Bodies?
-Cerebral Cortex (info processing, perception, thought, language)
-Limbic Cortex (emotions & behavior)
-Hippocampus (new memory formation)
-Midbrain & Basal Ganglia (movement)
-Brain Stem (sleep & alertness)
T or F: Women are at higher risk of suffering from Lewy Body Dementia.
False… Men are at higher risk!
How does Lewy Body Dementia clinically manifest?
-Intermittent memory problems
-REM Sleep Disorder (acting out dreams)
-Balance / Motor ctrl issues
-Emotionless face
-Hallucinations
-ANS effects (dizzy, hypotensive, falls)
What do we treat Lewy Body Dementia with?
-Is no direct treatment for the disease itself… Treat symptoms.
Cognitive: Alzheimer’s Drugs
Motor: Carbidopa / Levodopa
Behavior: AD’s / Antipsychotics
Sleep: Melatonin / Clonazepam
ANS: Fludrocortisone / Midodrine
Onset of Parkinson’s is what? Who’s most affected (M or W)?
50-70yrs ; Men more affected
How does Parkinson’s occur?
-Melanin production in Substantia Nigra induces oxidative stress on neurons, leading to misfolded Alpha Synuclein & formation of filamentous inclusions.
What happens to Dopaminergic projecting neurons in Parkinson’s Disease?
DIEEEEEEEE (so no projection from Substantia Nigra to Striatum)
What happens to neurons contained within the Substantia Nigra in Parkinson’s?
DIEEEEEEEEE (depigmentation of this brain region)
How do movement defects manifest clinically in Parkinson’s?
-Resting Tremor
-Rigid Movements
-Bradykinesia (Slow Movements)
-Shuffling Gait
Response to what pharmacological agent would help confirm Parkinson’s diagnosis?
Levodopa / Carbidopa
What other clinical manifestations would show up with Parkinson’s (aside from movement-related defects)?
-Expressionless Face
-Postural Instability
-Soft Voice
-Small Writing
-Hallucinations / Delusions (advanced disease)
What is the role of Carbidopa in Parkinson’s?
Reduces the systemic metabolism of Levodopa (so that it is able to reach the brain)
Which agents block Dopamine breakdown at the neuron?
Tolcapone
MAO-B Inhibitors (Selegiline, Rasagiline)
What agent reduces neuronal reuptake of Dopamine?
Amandatine
