A recent study, published on June 25, 2025, in Neurology®, the medical journal of the American Academy of Neurology, has drawn attention to the possible connection between neighbourhood disadvantage and early biological indicators linked to inflammation and Alzheimer’s disease. The researchers found that individuals residing in more socioeconomically challenged areas were more likely to exhibit elevated levels of biomarkers associated with both brain inflammation and neurodegeneration. Importantly, the study does not claim that living in such neighbourhoods causes these changes. Instead, it demonstrates a significant association, which adds nuance to the growing understanding of how environmental and socioeconomic factors might influence long-term brain health.
The study was led by Dr Angela L. Jefferson, a neuroscientist at Vanderbilt University Medical Centre and a member of the American Academy of Neurology. She noted that while previous research had already indicated a higher risk of Alzheimer’s disease among those living in disadvantaged neighbourhoods, little was known about the physiological mechanisms that might explain this risk. According to Jefferson, the findings suggest that chronic stressors associated with deprived environments may contribute to increased levels of inflammation within the body and brain. This inflammation, in turn, may lay the groundwork for the development of neurodegenerative diseases like Alzheimer’s, as well as directly raising levels of disease-specific biomarkers such as tau protein.
The longitudinal study followed 334 participants, with an average age of 73, over a period of nine years. Throughout this period, participants underwent regular cognitive tests, blood analyses, and brain imaging at intervals of 18 months, 3, 5, 7, and 9 years. Additionally, a subgroup of 180 individuals provided samples of cerebrospinal fluid, which allowed researchers to examine markers present in the central nervous system. This multifaceted approach enabled the researchers to track both the initial biomarker levels and how these levels changed over time, offering a more dynamic picture of disease development about neighbourhood conditions.
Neighbourhood disadvantage was calculated using an index that incorporated several key factors, including income, employment status, education levels, and rates of disability. Individuals residing in areas characterised by greater disadvantage were found to have higher concentrations of tau in their cerebrospinal fluid at the study’s outset. Tau is a protein that, when abnormally accumulated, is closely linked to the progression of Alzheimer’s disease. The researchers interpreted this as a possible indication that environmental stressors may contribute to early neurodegenerative changes in the brain, well before the onset of visible cognitive symptoms.
In addition to elevated tau, participants from more disadvantaged neighbourhoods also had higher levels of YKL-40, a protein associated with brain inflammation. These results remained consistent even after researchers accounted for a range of other factors that could influence biomarker levels, such as age, sex, and educational attainment. Furthermore, over time, researchers observed that levels of high-sensitivity C-reactive protein (CRP)—a well-known marker of systemic inflammation—rose more rapidly among individuals in disadvantaged areas. For every ten percentile increase in neighbourhood disadvantage, there was an associated yearly increase of 0.05 milligrams per litre in CRP levels. This pattern suggests a cumulative effect of chronic exposure to stressful or unhealthy environments, resulting in sustained inflammation throughout the body.
These findings carry important implications for public health strategies and medical practice. Dr Jefferson emphasised that healthcare providers should consider the broader social and environmental context when working with older adults or individuals at risk for cognitive decline. Lifestyle interventions aimed at reducing inflammation—such as regular physical exercise, a balanced diet, and stress-reduction techniques—could be particularly beneficial for individuals in high-risk communities. The study also highlights the importance of including individuals from disadvantaged backgrounds in clinical trials and preventive health studies, as these groups are often underrepresented in research but may benefit the most from targeted interventions.
However, the study’s authors acknowledged several limitations. Most notably, the participant pool was not fully representative of the broader U.S. population, as the majority were white, well-educated, and living in relatively less disadvantaged areas. As such, while the findings are valuable, they may not fully capture the experience of more severely disadvantaged or ethnically diverse populations. Further research will be necessary to confirm these trends across a broader demographic range and to gain a better understanding of how the lived experience of environmental hardship becomes biologically embedded in ways that affect brain ageing. Nevertheless, the study contributes essential insight into how place and circumstance intersect with biology to influence the risk of diseases like Alzheimer’s.
More information: Angela L. Jefferson et al, Cross-Sectional and Longitudinal Associations of Neighborhood Disadvantage With Fluid Biomarkers of Neuroinflammation and Neurodegeneration, Neurology. DOI: 10.1212/WNL.0000000000213770
Journal information: Neurology Provided by American Academy of Neurology
