Results of a new study at the University of Massachusetts Amherst suggest that people in midlife who are at genetic risk for Alzheimer’s disease might show subtle differences in the speed at which they process information compared to those who do not have particular genetic risk. These differences might be associated with changes in brain volume and could serve as markers to allow earlier detection and enhance chances for treatment.
Lead researcher Rebecca Ready, associate professor of psychology at UMass Amherst, says, “Alzheimer’s disease is a progressive neurodegenerative disease in which neuropathology begins to accumulate decades before clinical symptoms are noticeable. In order to maximize the opportunity for preventive interventions and treatment, it’s crucial that we identify early markers. Recent research is consistent with our results showing that a broader focus on early, preclinical markers for this disease is needed.”
“Our data suggest that investigators consider the possibility of subtle changes in processing speed even before clinical symptoms of mild cognitive impairment or Alzheimer’s disease become apparent. The most valuable data about early Alzheimer’s disease will come from long-term studies among high-risk populations, and we hope to expand our current sample and follow them over time to determine which neuropsychological and brain volume measures are related to future cognitive decline.”
Ready and colleagues’ report appears in the current issue of the American Journal of Alzheimer’s Disease and Other Dementias.
In this investigation supported by the UMass Amherst Research Development Office, she and colleagues used parental diagnosis of Alzheimer’s to recruit a genetically-enriched sample of 23 healthy, non-smoking adults (14 women, 9 men) with an average age of 55.8 years. As children of a parent with likely Alzheimer’s, they were considered to be at higher-than-average genetic risk. They agreed to genotyping and participated in several learning and memory, cognitive, motor and visual tests, a mood survey, a saliva assay for the stress hormone cortisol and an MRI.
The selection strategy yielded eight participants, or 35 percent of the original 23, who had the e4 variant of the genetic marker apolipoprotein (ApoE). ApoE e4 is associated with a three- to four-fold greater risk for Alzheimer’s than the estimated 14 to 25 per 100 rate in the wider population. The other 15 subjects had non-E4 variants or alleles of the Apo E gene.
Overall, ApoE e4 participants had similar education levels, verbal IQ scores, marital status, alcohol use, exercise habits, mood, stress levels, and good and bad life experiences over the previous year as participants who were not ApoE e4 positive, the authors say.
Participants attended two laboratory sessions. At the first, they took cognitive tests and were instructed how to collect and store cortisol samples by saliva swab at home over the next two days. Cognitive tests included measures of working memory, long-term memory storage, processing speed and visual scanning, among others. They also completed mood assessment, life events and personality tests. The second session, a few weeks after the first, was for MRI volumetric brain imaging.
Ready and colleagues compared measures for the eight participants in the ApoE e4 subgroup with results of the 15 participants who did not carry the e4 gene. They found that participants with the ApoE e4 marker performed significantly more slowly on an executive function test and had slower processing speed.
ApoE e4 subjects also had less brain volume in white matter. This lower white matter volume was significantly correlated with slower processing speed. “Processing speed and changes in white matter volume are candidate indicators of preclinical decline in Alzheimer’s disease,” Ready explains.
Finally, the ApoE e4 group had significantly greater morning rise in the stress marker cortisol as measured at waking and 30 minutes later, than the non-e4 group, but cortisol level was not associated with cognitive or brain volume measures. More research into associations between ApoE and cortisol is needed, the investigators note.
This study marks a break with past research by studying healthy people in midlife assumed to be at greater risk of developing Alzheimer’s disease than people who do not have a parent with the disease. “The vast majority of research on the effects of ApoE e4 on cognition and brain volume has been conducted on healthy, nondemented groups of older adults,” Ready notes. “We extended this line of research to a genetically-enriched, healthy sample of mid-life adults.”
