Human Brains Are Getting Bigger – What Does That Mean for Dementia Risk?

Human brains are getting larger, a characteristic that may offer some level of protection against age-related brain diseases. That’s according to a new study led by Dr. Charles DeCarli, professor and director at the University of California Davis Alzheimer’s Disease Research Center.

Brain development and size are, like many human traits, influenced by genetic and environmental factors. DeCarli and colleagues wanted to more closely explore the effects of the environment on the size of our brains. Their study, published in JAMA Neurology, measured differences in cranial and brain volume – and cortical thickness – in individuals born during the 1930s–1970s.

Brain magnetic resonance imaging (MRI) data was obtained from participants recruited to the Framingham Heart Study (FHS), a 75-year research project that was set up in 1948 to explore the incidence of conditions such as cardiovascular disease. The FHS is ongoing and now includes data from both second- and third-generation participants.

DeCarli and colleagues’ cohort comprised 3226 participants – 1706 females and 1520 males – who were born between the 1930s–1970s. On average, they were 57.5 years old at the time of their MRI and did not have a history of stroke or dementia.

Gradual increase in human brain size

Slow, but consistent increases in several brain structures were identified from the MRI data. Brain volume, or intracranial volume (ICV), showed a gradual increase decade by decade; participants born in the 1930s had an average volume of 1,234 mL, whereas participants born in the 1970s had an average volume of 1,321 mL – a 6.6% increase.

“We noted that ICV volume was greater with birth decade even when adjusting for height, sex and age, and this effect did not vary by sex,” the authors described. “These results suggest that ICV is likely increasing through secular trends either in processes different from those influencing height or the magnitudes of influence on these processes.”

Post-hoc analyses found that the largest secular effects for ICV, white matter and hippocampal volume occurred between the 1930s and 1940s.

The average surface area of the brain – or cortical surface area – also increased. Participants born in the 1970s had an average surface area of 2,104 cm², compared to 2,056 cm² for those born in the 1930s. Neurological structures such as white matter, grey matter and the hippocampus also increased in size from the 1930s cohort to the 1970s cohort.

Buffering the late-life effects of age-related brain diseases

DeCarli and colleagues’ study could help to explain data from a 2016 National Institutes of Health (NIH)-funded study of FSH participants. The number of people living with Alzheimer’s disease in the US is anticipated to reach 11.2 million by 2040. Despite this, the NIH researchers tracked the cognitive status of 5,205 FSH participants at 5-year intervals during four periods in the 1970s, 1980s, 1990s and 2000s, and reported a steady decline in new Alzheimer’s and related dementia cases since the 1970s. While the number of people living with dementia is increasing amongst our aging population, the NIH study suggests that the risk of dementia appears to be reducing.

Could an increase in brain size offer some level of protection? “Larger brain structures like those observed in our study may reflect improved brain development and improved brain health,” DeCarli said. “A larger brain structure represents a larger brain reserve and may buffer the late-life effects of age-related brain diseases like Alzheimer’s and related dementias.”

Causation cannot be established based on this work alone, however. “Longitudinal analyses showing secular differences in rates of regional brain atrophy would further support evidence of increased brain reserve through resilience to age-related atrophy,” the researchers explained.

While the study demonstrates that secular trends in brain structure are occurring, at least in the FSH cohort, an important limitation is that the FSH population is predominantly non-Hispanic White, healthy and well-educated individuals. “Current evidence indicates that social-cultural and health disparities, which are more common among non-White individuals in the US, may adversely affect brain health,” the authors said, which limits the generalizability of the findings.

Reference: DeCarli C, Maillard P, Pase MP, et al. Trends in intracranial and cerebral volumes of Framingham Heart Study participants born 1930 to 1970. JAMA Neurol. 2024. doi: 10.1001/jamaneurol.2024.0469

This article is a rework of a press release issued by the University of California, Davis. Material has been edited for length and content.