HMN 2026: How Alzheimer’s disease can be evaluated with brain stimulation

As individuals with Alzheimer’s disease (AD) move from the mild cognitive impairment stage to moderate and severe dementia, complex awareness deteriorates although lower-level sensory awareness is relatively maintained. Most conscious processes also become more impaired as AD progresses, including attention, working memory, episodic memory and executive function, while unconscious processes, such as procedural or muscle memory, operant conditioning (behavior controlled by consequences), and priming (where the experience of a stimulus affects the processing of a similar stimulus) are relatively spared.

However, as damage spreads across different cortical regions in dementias such as AD, corresponding aspects of conscious awareness become diminished and then lost.

How brain complexity is measured

One measure of brain complexity, the perturbation complexity index-state transitions (PCI-ST), can be calculated by recording EEG signals following a transcranial magnetic stimulation pulse. This measure has previously been used to determine when people are in a coma versus in a minimally conscious state. A new study asks whether this same measure could be used to evaluate the integrity of conscious processing in people with AD.

The work is published in the journal Neuroscience of Consciousness.

Key findings from the new study

According to researchers from Boston University Chobanian & Avedisian School of Medicine, the answer is yes. They have found that brain complexity in response to magnetic stimulation was reduced in people with AD compared with people aging normally.

“Despite their impaired conscious memory, individuals with Alzheimer’s disease may be able to use intact implicit, unconscious forms of memory, such as procedural memory (often termed ‘muscle memory’) to continue their daily routines at home. When they travel, however, their home routines are not helpful and their dysfunctional conscious memory can lead to disorientation and distress,” explains senior author Andrew Budson, MD, professor of neurology at the school.

The researchers assessed 28 participants with AD and 27 healthy controls, measuring their cognition and disease severity. They found lower PCI-ST in the AD group compared to controls across both the motor cortex and parietal stimulation sites, suggesting that PCI-ST may reflect the impaired conscious cognitive processes and functional capacity seen in AD.

Implications for future research and care

“This research opens the avenue for future studies in individuals with cortical dementia to examine the relationship between conscious processes, global measures of consciousness, and their underlying neuroanatomical correlates, in addition to enhancing our understanding of dementia and suggesting possible therapeutic strategies,” adds Budson, who also is chief of Cognitive & Behavioral Neurology and director of the Center for Translational Cognitive Neuroscience at the Veterans Affairs (VA) Boston Healthcare System.

Lead author Brenna Hagan, a Behavioral Neuroscience Ph.D. candidate at the school, points out that pharmacologic therapies, including donepezil (Aricept) and memantine (Namenda) alter neurotransmitters that can improve conscious abilities in those with Alzheimer’s disease. Additionally, non-pharmacological interventions can take advantage of relatively preserved procedural memory and other unconscious forms of memory to strengthen habits that may lead to improved quality of life.