Both normal aging and Alzheimer's change how different brain regions communicate with each other. But a new study from Lund University reveals that these alterations follow distinct patterns where shifts linked to disease are distinguishable from normal aging. And the alterations seen in Alzheimer's patients appear early, even before cognitive symptoms emerge. The discoveries are published in Nature Neuroscience.
The death of neurons in Alzheimer's disease leads to shrinking of certain brain regions, something that becomes pronounced relatively late in the disease. But the way different parts of the brain communicate – known as functional connectivity – also changes in the disease. However, connectivity changes occur during normal aging as well. Jacob Vogel, associate senior lecturer Lund University, and his team took a closer look at brain imaging from more than 1,000 people to investigate how communication between different parts of the brain changes with normal aging and the accumulation of Alzheimer's disease pathology.
"We already know that blood markers such as p-tau217 can reveal signs of Alzheimer's disease before cognitive symptoms appear. What surprised us was that the distinctive pattern of changes in brain communication was already apparent in people with low levels of Alzheimer's pathology who were still cognitively unimpaired," says Jonathan Rittmo, PhD student at Lund University and first author of the study.
Different patterns in aging and Alzheimer's disease
The researchers detected that connectivity alterations were not isolated to a single region-to-region change but rather emerged between several parts of the brain simultaneously, although along different axes in aging and disease. A healthy brain has several major organizational "directions" that describe how different types of regions communicate. This can be compared to a watercolor painting. Some colors are naturally more distinct from each other, while others are more similar. As brain connectivity changes, some of these differences fade, as if the colors were diluted, while others become sharper and more distinct. Importantly, these changes occur together in coordinated patterns across the brain.
"Our analyses showed that brain communication reorganizes in one specific pattern during normal aging, and in a very distinct and different pattern as Alzheimer's pathology accumulates," explains Jonathan Rittmo.
Aging and Alzheimer's pathology often occur at the same time, but the researchers' findings suggest that their effects on brain function are not simply different degrees of the same process but rather develop as distinct patterns. In Alzheimer's disease, communication patterns became more similar in higher-order brain regions involved in functions such as memory, while sensory and motor regions became more distinct. Normal aging showed a different pattern, with regions involved in executive functions becoming more similar and other regions more distinct. Jacob Vogel thinks that their findings propose a conceptual shift:
"Rather than treating connectivity increases and decreases as isolated effects in individual brain regions, our results suggest that they need to be interpreted as parts of larger patterns shaped by the brain's underlying organization."
Before connectivity patterns may be used to distinguish between Alzheimer's and normal brain aging, the group-level patterns found in the present study have to be confirmed in individual-level measures to see whether they predict subsequent cognitive decline. This work is ongoing.
Brain connectivity reflects cognitive function
In the present study, the connectivity pattern was more strongly related to cognitive function than to the accumulation of the Alzheimer's-related proteins amyloid-beta and tau in people with cognitive impairments. In the longer term, these connectivity patterns could potentially help identify brain changes associated with Alzheimer's before clear brain shrinkage or cognitive symptoms emerge. Monitoring brain connectivity could also be useful to evaluate effects of various interventions. Jacob Vogel is optimistic, as brain function is modifiable, for example through brain stimulation, cognitive tasks, or medication.
"If we can determine the downstream consequences of these connectivity patterns, for example if they reflect harmful system-level stress, this could eventually point toward ways of modulating them therapeutically, for example through non-invasive brain stimulation" he concludes.
