APOE, Brain Reserve and Cognition

1. Gene located on chromosome 19
2. involved in cholesterol transportation
   1. affect likelihood of development of CVD?
3. genotype determined by combination of 3 alleles
   1. e2, e3 or e4
   2. e2/2 = lowest risk
      1. e2 provides protection against dementia in old age
   3. e4/4 = highest risk
      1. 15% population prevalence of e4
      2. e4 carriers have
         1. smaller hippocampi
         2. greater hippocampal atrophy over time
         3. observed in demented and healthy individuals
         4. greater and more diffuse activation of hippocampal, prefrontal and parietal brain areas in memory tasks

            Annotations:

            • Bookheimer et al (2000)
         5. are e4 individuals less efficient in processing information?

Annotations:

• stern (2002) good clear review

1. buffers against pathological progression of dementia
2. individual differences in amount of reserve an individual possesses
3. passive

   Annotations:

   • Stern (2002) Stern et al (1999) Tisserand et al (2001)
   1. neuroanatomical structures deteriorate with age or disease until a threshold is breached, at which point cognitive impairment is manifest
   2. threshold*
4. active
   1. demographic or lifestyle factors contribute to reserves against deleterious consequences of ageing
      1. process tasks in more efficient manner
   2. Katzman (1993) - education increases synaptic density -> provides reserve against pathological progression
   3. brain is actively attempting to cope or compensate for pathology

      Annotations:

      • Stern (2002)
   4. cognitive reserve vs compensation
5. the mind's resistance to damage of the brain
   1. i.e. deficits in cognition may not be apparent even though damage has taken place?
6. hardware (brain reserve) vs software (cog reserve)

1. influence on brain reserve
   1. genetic predisposition to APOE + Vitamin B = episodic memory deficits?
2. differences observed in cognitive reserve between e4 compared to non e4 due to vitB?
3. ability to digest food efficiently decreases with age - not digesting enough B12?
4. low levels of B12 and folate associated with lower episodic memory performance in old age

   Annotations:

   • Calvaresi & Bryan (2001)

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

Annotations:

• see Bunce et al (2012)

1. e4 individuals have thinnest
   1. variation found in young people
2. one of the first areas to exhibit and be severely affected by neuropathology associated with AD