title: Multiple biological pathways link cognitive lifestyle to protection from dementia.
abstract: BACKGROUND
  An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans.
  
  
  METHODS
  Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS.
  
  
  RESULTS
  CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness.
  
  
  CONCLUSIONS
  An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways.
authors: Regenerative Neuroscience Group, School of Psychiatry, University of New South Wales, Sydney, Australia. michaelv@unsw.edu.au
authors: Michael J
authors: MJ
authors: Valenzuela
authors: Fiona E
authors: FE
authors: Matthews
authors: Carol
authors: C
authors: Brayne
authors: Paul
authors: P
authors: Ince
authors: Glenda
authors: G
authors: Halliday
authors: Jillian J
authors: JJ
authors: Kril
authors: Marshall A
authors: MA
authors: Dalton
authors: Kathryn
authors: K
authors: Richardson
authors: Gill
authors: G
authors: Forster
authors: Perminder S
authors: PS
authors: Sachdev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000473:pathology; D002452:Cell Count / Q000379:methods / Q000706:statistics & numerical data; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology; D003071:Cognition; D003704:Dementia / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D008019:Life Style; D008297:Male; D009474:Neurons / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology*; D012727:Sex Characteristics