I’ve reported before on the evidence suggesting that carriers of the ‘Alzheimer’s gene’, APOE4, tend to have smaller brain volumes and perform worse on cognitive tests, despite being cognitively ‘normal’. However, the research hasn’t been consistent, and now a new study suggests the reason.
The e4 variant of the apolipoprotein (APOE) gene not only increases the risk of dementia, but also of cardiovascular disease. These effects are not unrelated. Apoliproprotein is involved in the transportation of cholesterol. In older adults, it has been shown that other vascular risk factors (such as elevated cholesterol, hypertension or diabetes) worsen the cognitive effects of having this gene variant.
This new study extends the finding, by looking at 72 healthy adults from a wide age range (19-77).
Participants were tested on various cognitive abilities known to be sensitive to aging and the effects of the e4 allele. Those abilities include speed of information processing, working memory and episodic memory. Blood pressure, brain scans, and of course genetic tests, were also performed.
There are a number of interesting findings:
- The relationship between age and hippocampal volume was stronger for those carrying the e4 allele (shrinkage of this brain region occurs with age, and is significantly greater in those with MCI or dementia).
- Higher systolic blood pressure was significantly associated with greater atrophy (i.e., smaller volumes), slower processing speed, and reduced working memory capacity — but only for those with the e4 variant.
- Among those with the better and more common e3 variant, working memory was associated with lateral prefrontal cortex volume and with processing speed. Greater age was associated with higher systolic blood pressure, smaller volumes of the prefrontal cortex and prefrontal white matter, and slower processing. However, blood pressure was not itself associated with either brain atrophy or slower cognition.
- For those with the Alzheimer’s variant (e4), older adults with higher blood pressure had smaller volumes of prefrontal white matter, and this in turn was associated with slower speed, which in turn linked to reduced working memory.
In other words, for those with the Alzheimer’s gene, age differences in working memory (which underpin so much of age-related cognitive impairment) were produced by higher blood pressure, reduced prefrontal white matter, and slower processing. For those without the gene, age differences in working memory were produced by reduced prefrontal cortex and prefrontal white matter.
Most importantly, these increases in blood pressure that we are talking about are well within the normal range (although at the higher end).
The researchers make an interesting point: that these findings are in line with “growing evidence that ‘normal’ should be viewed in the context of individual’s genetic predisposition”.
What it comes down to is this: those with the Alzheimer’s gene variant (and no doubt other genetic variants) have a greater vulnerability to some of the risk factors that commonly increase as we age. Those with a family history of dementia or serious cognitive impairment should therefore pay particular attention to controlling vascular risk factors, such as hypertension and diabetes.
This doesn’t mean that those without such a family history can safely ignore such conditions! When they get to the point of being clinically diagnosed as problems, then they are assuredly problems for your brain regardless of your genetics. What this study tells us is that these vascular issues appear to be problematic for Alzheimer’s gene carriers before they get to that point of clinical diagnosis.
 . Age-Related Differences in Memory and Executive Functions in Healthy APOE ɛ4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure. Neuropsychologia [Internet]. Submitted ;50(5):704 - 714. Available from: http://www.sciencedirect.com/science/article/pii/S0028393212000103?v=s5