. Effect of Cognitive Reserve on Age-Related Changes in Cerebrospinal Fluid Biomarkers of Alzheimer Disease. JAMA Neurol. 2015 Jun;72(6):699-706. PubMed.


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  1. A possible physiological explanation for the inverse relationship between cognition and dementia that is worthy of consideration derives from the models of Raichle et al., 2001; Buckner et al., 2005, 2008; Cirrito et al, 2005; and Bero et al., 2011, on the activity of default mode network (DMN) neurons, cognitive resting-state conditions, and regional amyloid accumulation.

    The influence of neuronal activation on synaptic amyloid release, interstitial amyloid quantities, and regional amyloid accumulation has been described by Cirrito et al. and Bero et al.

    Buckner et al. proposed that accumulations of amyloid in the brains of subjects with Alzheimer’s disease overlap DMN regions that are persistently active or overactive during cognitive resting-state conditions in young adults.

    The proposed relationship between cognitive resting, increased DMN activity, and amyloid accumulation suggests that the protective effect of cognitive stimulation on the brain results from the effect cognitive challenges have on deactivating DMN regions that are vulnerable to amyloid. Perhaps "cognitive reserve" is a metaphor for the long-term effects that cognitive stimulation has on deactivating the DMN.

    Bero et al. proposed that education might be protective to brains, based in part on the putative relationship between neuronal activity and amyloid accumulation in the DMN. The proposal discussed by Bero et al. provides a possible physiological explanation for the inverse relationship between long-term cognitive enrichment and dementia. 


    . Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat Neurosci. 2011 Jun;14(6):750-6. Epub 2011 May 1 PubMed.

    . Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005 Aug 24;25(34):7709-17. PubMed.

    . The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008 Mar;1124:1-38. PubMed.

    . Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron. 2005 Dec 22;48(6):913-22. PubMed.

    . A default mode of brain function. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82. PubMed.

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  1. Cognitive Reserve—More Evidence It Prevents Neurodegeneration