Neurodegenerative Disorders

neurodegeneration

progressive dysfunction and loss of neurons → produces predictable circuit dysfunction

Parkinson’s disease

progressive neurodegenerative disorder

motor symptoms of Parkinson

bradykinesia, rigidity, resting tremor, postural/gait impairment

nonmotor symptoms of Parkinson

orthostatic hypotension, constipation, urinary dysfunction, sweating, autonomic dysfunction, mood & cognitive disturbances, sleep issues, dysphagia

pathology of Parkinson

α-synuclein accumulation associated with Lewy bodies; degeneration of substantia nigra dopamine neurons

stages of Parkinson

1) unilateral symptoms, minimal/no functional disability

2) bilateral symptoms, without balance impairment

3) bilateral, some postural instability, physically independent

4) severe disability, walk unassisted, assistance for activities

5) confined to wheelchair or bed unless assisted

risk factors of Parkinson

strongest risk factor is age

-genetic susceptibility, environmental (pesticide, head trauma)

basal ganglia

regulates movement, contains striatum

nigrostriatal pathway

SNc dopamine neurons project to striatum and modulate basal ganglia movement circuits

cellular dysfunction in Parkinson

cellular stress makes substantial nigra dopamine neurons move vulnerable to degeneration

-mitochondrial dysfunction, oxidative stress, impaired protein clearance

α-synuclein accumulation and Lewy pathology in Parkinson

α-synuclein proteins misfold & aggregate → accumulate in Lewy bodies in neurons → Lewy bodies become too big → progressive dopaminergic neuron loss

why are substantia nigra dopamine neurons vulnerable

they are constantly firing, so they are under high metabolic stress and have a sustained calcium load

motor effects of Parkinson caused by

loss of dopamine producing neurons

Alzheimer’s disease

characterized by degree of cognitive decline & effect on independent function

normal cognitive aging

slower recall, more time to learn, independence preserved

mild cognitive impairment

decline greater than expected for age

-may need reminders, complex tasks require more effort, mostly still independent

dementia

cognitive decline affects independence

types/causes of dementia

-Alzheimer’s (progressive, hippocampal & cortical networks, amyloid of tau pathology)

-vascular (brain vessel disease/stroke)

-vitamin B12 deficiency, thyroid, meds

risk factors of Alzheimer’s

largely age

-genetics, vascular/metabolic (diabetes)

clinical pattern of Alzheimer’s

-early (memory-predominant): difficulty learning, repeated questions, misplacing items, forgetting recent events, disorientation

-middle (broader cognitive decline): word finding difficulty, impaired judgement, more help with meds/meals

-late (global cognitive & functional decline): severe memory & communication impairment, behavioral symptoms, dependent

anatomical pathology of Alzheimer’s

cortical atrophy, ventricular enlargement, hippocampal atrophy

pathology of Alzheimer’s

-amyloid-ß and Tau disrupt synapses → cognitive decline

-loss of basal forebrain cholinergic neurons reduces ACh signaling → contributes to impaired cognitive function

amyloid-ß pathology

amyloid plaques form from accumulation of amyloid-ß; plaques associated with inflammation, synaptic dysfunction

-outside neurons

Tau

stabilizes microtubules

Tau pathology

Tau is abnormally phosphorylated, unravels, causing tangles → transport fails, neuronal dysfunction

-inside neurons

synaptic dysfunction & loss in Alzheimer’s

amyloid ß and tau disrupt synapses → cognitive decline