APOE, Brain Reserve and Cognition

APOE, Brain Reserve and Cognition

1. Apolipoprotein E

   • Gene located on chromosome 19
   • involved in cholesterol transportation
     • affect likelihood of development of CVD?
   • genotype determined by combination of 3 alleles
     • e2, e3 or e4
     • e2/2 = lowest risk
       • e2 provides protection against dementia in old age
     • e4/4 = highest risk
       • 15% population prevalence of e4
       • e4 carriers have
         • smaller hippocampi
         • greater hippocampal atrophy over time
         • observed in demented and healthy individuals
         • greater and more diffuse activation of hippocampal, prefrontal and parietal brain areas in memory tasks
           • Bookheimer et al (2000)
         • are e4 individuals less efficient in processing information?

2. Brain Reserve

   • stern (2002) good clear review
   • buffers against pathological progression of dementia
   • individual differences in amount of reserve an individual possesses
   • passive
     • Stern (2002) Stern et al (1999) Tisserand et al (2001)
     • neuroanatomical structures deteriorate with age or disease until a threshold is breached, at which point cognitive impairment is manifest
     • threshold*
   • active
     • demographic or lifestyle factors contribute to reserves against deleterious consequences of ageing
       • process tasks in more efficient manner
     • Katzman (1993) - education increases synaptic density -> provides reserve against pathological progression
     • brain is actively attempting to cope or compensate for pathology
       • Stern (2002)
     • cognitive reserve vs compensation
   • the mind's resistance to damage of the brain
     • i.e. deficits in cognition may not be apparent even though damage has taken place?
   • hardware (brain reserve) vs software (cog reserve)

3. Vitamin B12

   • influence on brain reserve
     • genetic predisposition to APOE + Vitamin B = episodic memory deficits?
   • differences observed in cognitive reserve between e4 compared to non e4 due to vitB?
   • ability to digest food efficiently decreases with age - not digesting enough B12?
   • low levels of B12 and folate associated with lower episodic memory performance in old age
     • Calvaresi & Bryan (2001)

4. Antagonistic Pleiotropy

   • comes from evolutionary theory
   • does a gene confer benefits in early life but become a risk factor for disease in later life?
     • e.g. testosterone
   • e4 associated with better cognitive performance in childhood/ early adulthood but deficits in old age
     • suggests a pleiotropic relationship between e4 and cognition across lifespan
   • NO evidence in support of this

5. entorhinal cortex

   • see Bunce et al (2012)
   • e4 individuals have thinnest
     • variation found in young people
   • one of the first areas to exhibit and be severely affected by neuropathology associated with AD