The development and upkeep of the human brain are influenced by both genetic factors and environmental conditions, which may subsequently impact the risk of dementia later in life. Thus, a recent study published in JAMA Neurology assessed whether there were changes in skull and brain size, as well as the thickness of the cortex, across individuals born between the years 1930 and 1970.
Study: Trends in Intracranial and Cerebral Volumes of Framingham Heart Study Participants Born 1930 to 1970. Image Credit: Gorodenkoff/Shutterstock.com
Background
The health of the American populace has improved significantly due to advancements in healthcare diagnostics and treatment strategies, resulting in an extended average lifespan. However, this increase in longevity also brings a higher likelihood of encountering Alzheimer’s disease and other forms of dementia, as well as various conditions prevalent in older age.
Fortunately, the dementia incidence is decreasing, perhaps in part because of more education and better preventive measures for cardiovascular risk. Another important contributor may be the early environment.
The Framingham Heart Study cohort (FHS) includes many generations of people, followed up over decades. The difference between the earliest and latest subjects to be enrolled in the cohort spans over 80 years.
This led the researchers in the current study to draw their cohort from this study group, examining trends in cardiovascular and brain health in successive generations.
The aim was to look for a predicted increase in brain development in the US population due to changing early life environment trends. This would reflect in larger brain volumes.
About the study
All participants were born between 1925 and 1968. None had been diagnosed with dementia or stroke, and all had undergone magnetic resonance imaging (MRI) between 1999 and 2019. The mean age at MRI varied with the decade of birth but with overlap between decades.
What were the findings?
There were over 3,200 participants, the mean age at MRI being 58 years. The images revealed that multiple brain volume measurements showed an upward trajectory with the later birth cohorts.
The investigators measured intracranial volume (ICV), hippocampal volume (HV), cortical surface area (CSA), cortical gray matter volume (CGMV), and white matter volume (WMV). Females were observed to be 5.5 inches shorter on average, with lower HV, CGMV, and WMV.
The difference in hippocampal volume was by -0.64 mL, while males had ~54 mL and 63 mL greater volumes for gray and white matter, respectively.
The 1930s birth cohort had a mean height of 66 inches vs 68 inches for the 1970s birth cohort. The average ICV increased by over 6%, at 1321 mL in the 1970s vs 1234 mL in the 1930s cohort, respectively. This was after compensating for confounding factors like age, sex, and height.
Regional measures also varied with the birth cohort, showing a definite trend. Both HV and WMV went up with the decade of birth. So did the CSA, while the cortical thickness decreased, implying cortical atrophy.
Comparing the 1930s to the 1970s cohort, the largest increase was for CSA, which increased by 15%. The WMV and HV increased by 8% and 6%, respectively, but CGMV by 2%. The cortical thickness declined by over a fifth, from 2.3 mm to 1.9 mm, respectively. There was no significant difference between the sexes.
Even after limiting the analysis to only those born in the 1940s and aged 55 to 65 years, the same trends were observed, though the differences were attenuated. For instance, the increase in WMV and CGMV were only 0.2% and 0.1%, respectively.
What are the implications?
The study results indicate that later generations are experiencing increased brain volume, both overall and regional. The difference was greatest for ICV, WMV, and HV, when the 1930s and 1940s cohorts were compared.
“We hypothesize that larger brain volumes indicate larger brain development and potentially greater “brain reserve” that could explain the declining incidence of dementia.”
The ICV reflects normal brain development and does not go down with aging or diseases affecting the volume. In fact, the adult ICV predicts cognitive levels in old age and provides a reliable and consistent biomarker for brain size.
HV loss may occur early in neurodegenerative conditions, including Alzheimer’s,
The larger cortical WMV in later cohorts might be the result of greater gyrification, leading to larger CSA. The increased WMV indicates higher neuronal connectivity while reducing the effects of brain tissue loss with aging. The increase in CSA with a reduction in cortical thickness supports this explanation.
The presence of gyri in the brain increases the brain CSA by 1,700 times compared to the brain of a shrew but limits the increase in cortical thickness to six times. Genes regulate different brain regions differently to develop gyri to various extents.
The increase in larger brain structures is due to changes in early life experiences, including better education, social environment, and health status. The better preventive measures for cardiovascular disease may be responsible as well. Thus, modifying these factors could also improve resistance to late-life dementia.
At the population level, these effects may be very important, helping to optimize brain development and building cognitive resilience over the decades.
Some genetic mutations may offer protection against developmental disorders