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. Author manuscript; available in PMC: 2011 Oct 1.
Published in final edited form as: J Am Geriatr Soc. 2010 Oct;58(Suppl 2):S313–S318. doi: 10.1111/j.1532-5415.2010.02982.x

TABLE 1.

Selected non-normative influences on cognitive trajectories by mechanism

Neurodegenerative Proteinopathies Cerebrovascular Systemic/Homeostatic
β-amyloidopathy Stroke Stress, pain, sleep
Tauopathy White matter degeneration (leukoaraiosis) Emotional dysregulation
α-synucleinopathy Diabetes, hypertension, dyslipidemia Diabetes, hypertension, dyslipidemia
TDP-43opathy Cardiorespiratory insufficiency CNS inflammation
Hippocampal sclerosis Hippocampal sclerosis Medications, toxins

CNS=Central nervous system. β-amyloid, tau, α-synuclein, and TDP-43 (Transactivation response DNA binding protein) are examples of proteins which aggregate and are detectable via pathologic evaluation in neurodegenerative diseases. Note that mechanistic categories may not be entirely distinct, for example if ischemic changes lead to neurodegeneration. As such, pathobiologic conditions may pertain to more than one category.