“Having a big head may protect against dementia,” reported the BBC. The news report said that research in 270 patients with Alzheimer’s disease found that a larger head size (as a marker of brain size) was linked to better performance in cognitive tests, even when patients had the same amount of brain loss assessed by MRI scan.
This was a preliminary study that requires further research in a larger group of people. It is important to highlight that brain size is largely determined by genes and it is not clear whether it is possible to influence brain size during childhood sufficiently to promote greater brain function resilience following brain loss in later life.
However, researchers hope that understanding how the brain compensates after being damaged by Alzheimer’s disease may help to develop strategies to keep enhanced function for longer in patients with the condition.
Where did the story come from?
The study was carried out by researchers from the Technische Universität München in Germany, the University of Cambridge, Boston University School of Public Health and the University of California at Davis. It was funded by The National Institute on Aging in the US. The study was published in the (peer-reviewed) medical journal Neurology .
What kind of research was this?
This cross-sectional study in people with Alzheimer’s disease (AD) explored how the size of a person’s brain and the amount of brain cell death they had affected their symptoms of AD.
What did the research involve?
The researchers used data from the Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) study, an ongoing multi-centre study looking for genetic and environmental risk factors for AD. The data included information on participants’ risk factors for Alzheimer’s disease, blood samples for genetic testing and MRI scans of their brains. There was also information on the participants’ degree of cognitive impairment, assessed by a test called the Mini-Mental State Examination (MMSE).
The researchers used the MRI scans to assess the proportion of brain loss in each patient. They also assessed what variant of the APOE gene (associated with Alzheimer’s disease) each participant had.
For this study, the researchers made an additional measurement of head circumference in 270 patients with Alzheimer’s disease using a tape measure. These patients had Alzheimer’s disease symptoms for an average of five and a half years, and were 70 years of age when symptoms began. These new measurements were compared with the participants’ medical data from the MIRAGE study to estimate the relationship between brain cell loss and loss of cognitive function and whether the brain size of the patient affected this.
What were the basic results?
The researchers found that people who had Alzheimer’s disease for a shorter time achieved higher scores on the MMSE test (indicating less cognitive impairment) and were associated with less brain loss. People with lower MMSE scores tended to be older, but there was no association between head circumference and the score that people achieved on the MMSE test.
MMSE scores were unaffected by ethnicity or other medical conditions such as diabetes or depression. The scores were also unaffected by whether or not a person carried the APOE variant, as those who did carry it had similar scores on the test to people who did not.
The researchers modelled the association between brain loss and MMSE score using a statistical technique called multiple linear regression. Although previous analysis had shown no association between head circumference and cognitive ability, the regression testing showed that head circumference influenced the relationship between the degree of brain loss and brain function. This meant that a larger head circumference was associated with a reduced effect of brain loss on brain function (p=0.04, β=-0.21).
How did the researchers interpret the results?
The researchers say that larger head circumference reduced the association between brain cell loss and cognitive impairment.
They also say that, as human brains reach 93% of their full size by the age of six, “optimal neural development” in these early years may provide a buffer for later in life. Although this is mostly predetermined by genetics, other external influences, such as nutrition and brain diseases, can also have an effect. They suggest that targeting these factors in early life may affect the risk of developing Alzheimer’s in later life.
This preliminary study found that a larger head circumference (as an indicator of brain size) was associated with less brain cell death and fewer symptoms of Alzheimer’s disease. The researchers highlighted the following limitations to their study.
- The patients were recruited for the study at specialised memory clinics. As such, these patients may not be representative of the wider Alzheimer’s disease population as they may have received different care.
- Brain loss was graded by the researchers themselves by visually examining the MRI scans. In hindsight, the researchers suggest that a computerised approach to measuring brain volumes would have reduced the likelihood of human error.
- Head circumference was used to estimate brain size. Although this is a widely accepted way of indirectly measuring brain size, a computer measurement of the inside volume of the skull may have provided more accurate measurements of brain size.
- The study only made one measurement of brain loss and used only the most recent assessment of brain function. Further research would be needed to see whether these associations were maintained over time.
This was a preliminary study, which warrants further research on a larger group of people. It is important to highlight that brain size is largely determined by genes and it is not clear whether it is possible to influence brain size during childhood and therefore to promote greater brain function resilience following brain loss. However, understanding how the brain compensates after being damaged by Alzheimer’s disease may help to develop strategies to promote enhanced function for longer in patients with Alzheimer’s disease.