Mild behavioural impairment a warning signal for neurodegeneration

People who report symptoms of mild behavioural impairment exhibit pronounced cortical thinning in regions involved in emotion regulation, belief formation, and cognitive control in the right side of the brain, according to a study.

In a cross-sectional cohort from the Biomarkers and Cognition Study in Singapore, higher scores on the Mild Behavioral Impairment Checklist (MBI-C) Belief subdomain significantly correlated with MRI-assessed cortical thinning in the right hemisphere (p=0.035). Region-specific analyses showed temporal lobe thinning in the posterior superior temporal sulcus (p=0.013), fusiform gyrus (p=0.009), superior temporal gyrus (p=0.025), temporal pole (p=0.021), and transverse temporal gyrus (p=0.014). [Biol Psychiatry Cogn Neurosci Neuroimaging 2025;doi:10.1016/j.bpsc.2025.06.010]

The associations persisted despite false discovery rate (FDR) correction, with additional correlations observed between higher MBI-C Belief subdomain scores and cortical thinning in the right postcentral gyrus, supramarginal gyrus, and insula (FDR, p≤0.039).

A total of 969 participants (mean age 61.99 years, 39.6 percent male, 87.2 percent Chinese) were included in the analysis. Of these, 34.3 percent were classified as cognitively normal, 26.4 percent as having subjective cognitive decline, and 39.3 percent as having mild cognitive impairment.

“Notably, individuals with subjective cognitive decline exhibited higher MBI-C total and subdomain scores than those who were cognitively normal or had mild cognitive impairment. This finding may reflect heightened self-awareness or hypervigilance, leading to increased reporting of early neuropsychiatric symptom that precede overt cognitive impairment,” said lead study author Yi Jin Leow from Nanyang Technological University and colleagues. [J Alzheimers Dis 2021;80:459-469; Eur Arch Psychiatry Clin Neurosci 2014;264:3-7]

“Elevated symptom reporting may also reflect early affective disturbances and compensatory mechanisms before objective deficits emerge,” they added. [JAMA Neurol 2017;74:1455-1463]

Leow and colleagues highlighted the potential implications of their findings, noting that pronounced thinning in the temporal lobes—which are crucial for memory and semantic processing—occurs in the early stages of Alzheimer’s disease (AD). [Brain 2007;130:1159-1166; Brain 2007;130:708-719]

They also pointed out that AD is characterized by extensive neurodegenerative changes, including parietal thinning and insular atrophy, which are linked to impaired spatial awareness and attention and disrupted emotional and cognitive integration, respectively. [Cereb Cortex 2009;19:497-510; Alzheimers Res Ther 2023;15:114; Neurobiol Aging 2015;36:903-908]

Overall, the findings underscore the potential of mild behavioural impairment as an early biomarker of neurodegeneration, reflecting subtle structural brain changes that may precede overt cognitive decline, according to Leow and colleagues. “This supports the clinical utility of behavioural assessments such as the MBI-C in detecting prodromal AD and related dementias.”

They called for longitudinal studies in larger, multi-ethnic cohorts to clarify the temporal dynamics between neuropsychiatric symptoms and cortical atrophy, which can guide early diagnostic and precision intervention strategies.