Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Roberts RO, Lowe VJ, Kantarci K, Senjem ML, Gunter JL, Boeve BF, Petersen RC, Jack CR. Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Ann Neurol. 2012 Nov;72(5):730-8. PubMed.
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This is an interesting article. I do think it is one of a growing number of reports that factors associated with cognitive reserve (CR) may actually directly affect Alzheimer pathology. We also have a previous report (Lo et al., 2013) in which we looked at longitudinal change in CSF and found that education, occupation, and ANART scores were associated with slower change in Aβ. There have also been studies from our group (see Landau et al., 2012; Wirth et al., 2014) on relationships between cognitive activity and PIB PET measures of Aβ. And the Washington University group has reported similar results for physical activity and PIB measures of Aβ (Head et al., 2012; Liang et al., 2010). So all in all there are quite a lot of papers suggesting that “lifestyle” variables may affect risk for AD directly through effects on AD pathology. There are a few other papers I haven’t mentioned. CR is one of these potential lifestyle variables.
However, not all such studies agree. The Mayo group (Vemuri et al., 2012) in particular had a very large study that did not find such associations.
This is a very complicated area. This paper, in particular, is a bit different from others in two ways. First, the major finding seems to be CSF tau, and second, the effect appeared in the relationships between age and tau—that is, CR attenuated the association between advancing age and higher tau. This is similar to a previous study from this group showing an effect of physical activity on age-related Aβ increases (also memory and hippocampal volume). One can, I suppose, consider these findings all in agreement or not. There does seem to be a trend in the literature associating a variety of lifestyle factors with AD biomarkers. However, the lifestyle factors differ considerably and are measured and categorized in very different ways, and the biomarkers also differ and seem to include both Aβ and what many people consider “downstream” effects of Aβ. I guess you can draw two conclusions from all this: (1) there is growing information that lifestyle directly affects AD biomarkers, not simply the “response” to such biomarkers, and (2) the data are not in agreement about what lifestyle factors are important nor what biomarkers are affected.
References:
Lo RY, Jagust WJ, . Effect of Cognitive Reserve Markers on Alzheimer Pathologic Progression. Alzheimer Dis Assoc Disord. 2013 Apr 1; PubMed.
Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O'Neil JP, Wilson RS, Jagust WJ. Association of Lifetime Cognitive Engagement and Low β-Amyloid Deposition. Arch Neurol. 2012 Jan 23; PubMed.
Wirth M, Villeneuve S, La Joie R, Marks SM, Jagust WJ. Gene-environment interactions: lifetime cognitive activity, APOE genotype, and β-amyloid burden. J Neurosci. 2014 Jun 18;34(25):8612-7. PubMed.
Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T, Holtzman DM, Morris JC. Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition. Arch Neurol. 2012 Jan 9; PubMed.
Liang KY, Mintun MA, Fagan AM, Goate AM, Bugg JM, Holtzman DM, Morris JC, Head D. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann Neurol. 2010 Sep;68(3):311-8. PubMed.
Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Roberts RO, Lowe VJ, Kantarci K, Senjem ML, Gunter JL, Boeve BF, Petersen RC, Jack CR. Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Ann Neurol. 2012 Nov;72(5):730-8. PubMed.
Mayo Clinic and Foundation
While there has been a recent flurry of papers investigating CR, biomarkers, and cognition, there is no clear consensus on these interrelationships. The sample characteristics, measures of CR, and cognition appear to greatly influence the picture. However all the studies as well as this one have found that CR may be helpful in reducing the deleterious effects of dementia. This study found that higher CR was associated with a diminution of age-related alterations in CSF biomarkers (specifically neuronal injury biomarkers) of AD, supporting the prevailing idea that higher CR is helpful. One major drawback of the study is the inclusion of both younger cognitively normal and older cognitively impaired because non-age-matched subjects may not accurately represent the CN-MCI-mild AD spectrum and will influence the age and biomarker associations in the overall association analyses.
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