Select Neurodegenerative Diseases. Alzheimer’s Disease.

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Presentation transcript:

Select Neurodegenerative Diseases

Alzheimer’s Disease

Dementia vs. Alzheimer’s -Dementia is an umbrella term that covers many disease states -Interesting relationship between decades and likelihood of having the disease -Myriad of diseases that qualify -History plays a key role in initial diagnosis -Alzheimer’s is a specific diagnosis for dementia -Analogous to a sore throat vs. strep throat

History of Alzheimer’s -Until 1991: No animal models w/ Ab -Now transgenics w/ Ab & tau -Until 1993: Did not know any genes -Now 3 early onset genes; one late-onset risk factor -Until ~1998: No prevention trials -Now: lots

Epidemiology -4.5 million people over the age of 65 in the U.S. are afflicted -700 thousand between years of age -2.3 million between years of age -1.8 million 85 years and older -Early onset dementia -Rare occurrence -Predominantly caused by Alzheimer’s -No clear gender distinction -More women are currently diagnosed with Alzheimer’s -Genetics -Family history plays a role -Dementia in general is on the decline

Diagnosis -Can be very difficult -Only definitive diagnosis is an autopsy -History is extremely important

Mild Cognitive Impairment -Concern by pt/family/others re memory/thinking -Does not impair everyday activities -Objective evidence for impairment in >1 or domains -e.g., Recent memory, language, visual spatial, exec. fun. -Not demented -Rule out other causes: bleeds, tumor, endocrine factors etc. -Not clear who will convert to AD and who will not

General Dementia -Impaired social & instrumental activities of daily living -IADL’s: e.g. managing money, cooking/shopping, using phone -A decline from previous levels -Deficits Not explained by: -Delirium temporary, sudden (hrs/days) confusion/awareness fluctuation -b/c of drugs, ethanol, metabolic problems, infection etc. -Psychiatric disorders like depression -Cognitive impairment detected via Hx & by cognitive testing -Impairment in at least 2 of the following domains: -Recent memory, judgment, visuospatial, language, personality

Probable AD Dementia -Meets general criteria for dementia -Rule out other causes of cognitive impairment, e.g. -Thyroid problems -Vitamin B12 deficiency -Lesions/tumors/bleeds via standard MRI3 -Gradual onset -Slow progression -Deficits in recent memory -Visuospatial deficits -Deficits in other domains, e.g., anomia, alexia, math -Executive function deficits, e.g., judgment/reasoning

Treatment Options -Acetylcholine promoters -cholinesterase inhibitors -NMDA receptor blocker -Antioxidant Therapy -Vitamin E -Selegiline

Parkinson’s Disease

Neurodegenerative disease CNS (Central Nervous System) Mostly affects the motor cortex. Death of dopamine-releasing cells in the substantia nigra.

Epidemiology -0.3% of individuals older than 40 -Approximately 7.5 million people worldwide -Risk of developing Parkinson’s Disease increases with age -Family history -Men may be at greater risk than women

Clinical Presentation Early symptoms → movement-related shaking, rigidity, slowness of movement, difficulty walking and characteristic gait Later symptoms → cognitive dementia, depression "Substantia nigra" by FrozenMan - Own work. Licensed under CC BY-SA 4.0 via Commons - Substantia nigra

Cause -Depletion of dopamine from the basal ganglia -disrupts connections to motor cortex and thalamus. -Leads to bradykinesia (slow movement) Genetics -Most cases are sporadic. (No known genetic contribution) -Some cases are familial. (Genetic contribution) -Parkin genes: PARK1 → PARK13

Diagnosis - difficulties -No physiologic or blood tests. -Imaging can rule out other diagnoses (tumor, infarcts) -Genetic testing -Mutations in SNCA, Parkin (PARK2), PINK1 (PARK6), DJ-1 (PARK 7), and LRRK2 (PARK8) -Difficult to interpret… -Presence of Lewy Bodies in substantia nigra -Abnormal protein accumulations -Only in autopsy, so can’t do this with living patient -Main finding in post-mortem "Lewy Body alphaSynuclein" by Marvin Own work. Licensed under CC BY-SA 3.0 via Commons

Making the diagnosis -Neuropathologic examination -Bradykinesia (slowness of movement) -Plus tremor and/or rigidity -Poor diagnostic accuracy at initial visit (~26%) -Response to dopaminergic therapy -Do symptoms improve after treatment with L-DOPA or apomorphine?

Treatment (if the disease is caused by loss of dopamine, then...) No cure, only treatments. Levodopa (L-dopa) Dopamine agonists Anticholinergics MAO B inhibitors Amantidine COMT inhibitors Deep-brain stimulation For advanced Parkinson’s Disease

Assistive Technologies

Amyotrophic Lateral Sclerosis

Epidemiology -Sporadic % -Approximately 2 per 100,000 -Incidence and mortality rate on the rise -Familial -5-10% -Earlier disease onset (mean age 56.3 versus 61.3 years) -Higher frequency of comorbid FTD (50 versus 12 percent) -Shorter age-matched median survival (20 versus 26 months)

Clinical Presentation -Upper Motor Neuron Signs -Spasticity -Slowed muscle movements -Babinski sign -Lower Motor Neuron Signs -Weakness -Atrophy -Fasciculations

Diagnosis El Escorial Criteria Evidence of lower motor neuron degeneration by clinical, electrophysiological, or neuropathological examination Evidence of upper motor neuron degeneration by clinical examination Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination. Lower motor dysfunction: weakness, atrophy, fasciculations Upper motor dysfunction: increased deep tendon reflexes, reflexes in wasted muscles, Hoffman sign. “Pseudobulbar affect”: inappropriate laughing or crying, or forced yawning

Hoffman Sign

Treatment No cure. Riluzole is the only available drug to increase life expectancy 12 month survival rate increases from ~60 to 75% Management of symptoms Dysarthria (Speech loss) → Alternative communication (writing, electronic speech) Dyspnea (breathing problems) → artificial ventilation, treatment of pneumonia Muscle spasms → quinine (or alternatives) Sialorrhea (drooling) → various medications Pain → painkillers, including opioids Psychosocial issues → antidepressants, ???