Functional imbalance of two brain networks might predict cognitive decline in Alzheimer’s disease

A neuroimaging study of individuals spanning the Alzheimer’s disease spectrum found that the attenuated anticorrelation (reduced negative association) between the activity of the default mode network and the dorsal attention network of the brain predicted cognitive decline. The association between this anticorrelation and cognitive decline did not depend on education level, a known protective factor against cognitive decline. The research was published in NeuroImage.

Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects memory, thinking, and behavior. It is the most common cause of dementia, accounting for up to 70% of all dementia cases. The disease is characterized by the accumulation of abnormal proteins in the brain—beta-amyloid plaques and tau tangles—that disrupt communication between neurons.

Over time, these accumulations lead to the death of brain cells, causing shrinkage of key regions involved in learning and memory, such as the hippocampus. One of the earliest symptoms is mild forgetfulness that gradually worsens into severe memory impairment. Cognitive decline in Alzheimer’s affects not only memory but also reasoning, problem-solving, language, and spatial orientation.

As the disease progresses, individuals become disoriented, have difficulty recognizing familiar people or places, and struggle with everyday tasks. Emotional and behavioral changes such as apathy, irritability, or anxiety often accompany cognitive deterioration. While age is the strongest risk factor, genetics, cardiovascular health, and lifestyle also play important roles.

Study author Diego-Martin Lombardo and his colleagues note that the accumulation of abnormal proteins starts many years before the first cognitive symptoms appear. This means that Alzheimer’s disease has a long period of development with no symptoms. Because of this, it is important to develop ways to detect the development of Alzheimer’s disease in the early stages, while cognitive symptoms have not yet appeared.

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The study authors hypothesized that one such early indicator of Alzheimer’s disease might be the anticorrelation between two important brain networks: the default mode network and the dorsal attention network. The default mode network, or DMN, is a brain network active during rest, daydreaming, and while a person is thinking about oneself or introspecting.

The dorsal attention network, or DAN, is a brain network engaged during goal-directed attention, focusing on external stimuli, and controlling voluntary attention. Typically, the activity of these two networks is anticorrelated, meaning that when the activity of one of them increases, the activity of the other decreases, and vice versa.

The researchers analyzed functional magnetic resonance imaging (fMRI) data of 182 individuals from one of the datasets belonging to the Alzheimer’s Disease Neuroimaging Initiative, or ADNI. ADNI is a large, long-term research project that collects and shares clinical, imaging, genetic, and biomarker data to study the progression of Alzheimer’s disease and improve its early diagnosis and treatment. The participants’ average age was approximately 70 years, and 59% of them were men.

The authors classified participants into four groups based on whether they showed cognitive impairment and whether abnormally high levels of beta-amyloid protein deposits were detected in their brains. This differentiation allowed researchers to distinguish between different stages of cognitive decline and Alzheimer’s disease progression.

Results showed that anticorrelation between DMN and DAN was weaker in the group that both had cognitive impairment and abnormal levels of amyloid plaque in their brains. The combination of high concentrations of these abnormal proteins and cognitive impairment indicates that these individuals are at a high risk of Alzheimer’s disease or that it has already been developing for some time.

Further analyses indicated that reduced DMN-DAN anticorrelation predicted cognitive decline even after taking into account sex, age, education, and the concentrations of tau proteins (another type of abnormal protein with high concentrations in the brains of individuals with Alzheimer’s disease).
Most interestingly, this association between DMN-DAN anticorrelation and cognitive decline did not depend on education level. Education level is generally an indicator of cognitive reserve—the brain’s ability to modify its pathways to cope with damage and age-related changes. Cognitive reserve is widely believed to be a protective factor against age-related cognitive decline.

“We demonstrate that the attenuation of the anticorrelation between DMN and DAN is associated with a mechanism of cognitive dysfunction independent of tau pathology and proxies of resilience to cognitive decline or cognitive reserve. Our results also suggest the existence of an alternative mechanism of neurocognitive breakdown independent of advanced medial temporal cortex pathology and protective factors of cognitive decline, such as cognitive reserve,” study authors concluded.

The study contributes to the scientific understanding of the neural bases of Alzheimer’s disease. However, the design of the study does not allow any causal inferences to be derived from the results. Therefore, it remains unknown whether the reduced DMN-DAN anticorrelation is one of the causes of cognitive decline seen in Alzheimer’s disease or is a consequence of this decline.

The paper, “The intrinsic connectivity between the Default Mode and Dorsal Attention networks is an independent fMRI biomarker of Alzheimer’s disease pathology burden,” was authored by Diego-Martin Lombardo, Christian F. Beckmann, and the Alzheimer’s Disease Neuroimaging Initiative.