Can white matter changes in the brain determine our ageing trajectory? Premium

Discover how white matter changes in the brain can predict aging trajectories and cognitive decline in individuals.

Ageing is a major risk factor for most neurological and psychiatric disorders. As populations worldwide continue to grow older, the burden of brain- and cognition-related disorders is expected to rise substantially. There is, therefore, an urgent need to understand the normal trajectory of brain ageing and to develop scientific methods that can determine and predict whether an individual is following a healthy ageing path or is at risk of developing cognitive disorders later in life.

Normal ageing is associated with well-defined changes in brain structure and behaviour. Accelerated changes in brain structure and function beyond this typical trajectory are believed to increase the risk of age-related disorders and may lead to their earlier onset. Central to brain function are the white-matter regions, which consist of axonal fibre tracts responsible for communication and connectivity between different parts of the brain. These fibre tracts, insulated by myelin, are essential for efficient information transfer.

In our research, published in November 2025 in Cerebral Cortex we focused on the health of brain white matter, with an underlying quest to measure the extent of white-matter changes as a quantitative feature that could determine brain health and the ageing trajectory. With the usual ageing process, white matter fibres undergo gradual pruning and degeneration from infarction of the brain’s smallest blood vessels. Brain MRI measurements allow this damage to be detected as white-matter hyperintensities (WMH) in regions near the brain’s ventricles, as well as in deep white matter. These changes accumulate in nearly everyone with age, but not at the same rate. A subset of individuals experiences relatively slow/no accumulation, while others show a much faster deposition of WMHs.

Using a large global ageing consortium, including the U.S.’s National Alzheimer’s Coordinating Center, the multi-centre Alzheimer’s Disease Neuroimaging Initiative, and an Indian meta-cohort of Indian Institute of Science Education and Research, Berhampur, we conducted comprehensive quantitative brain imaging and cognitive investigations to pinpoint white matter changes as an index to map global brain health and brain age.

The central question was to determine when changes that occur in everyone with age begin to interfere with normal brain function.

Our research revealed a clear biological tipping point in the brain aging trajectory, defined by a critical burden of WMH on a brain MRI, beyond which brain tissue loss and cognitive inefficiency increase disproportionately. When WMH volume exceeds approximately 2.5 mL, individuals are more likely to exhibit structural brain loss and impairments in everyday cognitive functions, including reaction time, attention, planning, multitasking, and word retrieval. Importantly, these changes can occur even when standard memory measures and global cognitive tests remain within the normal range.