Brain complexity declines in Alzheimer's disease

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 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 becomes diminished and then lost.

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 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. 

According to researchers from Boston University Chobanian & Avedisian School of Medicine, the answer is yes. They 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."

Andrew Budson, MD, senior author, professor of neurology, Boston University Chobanian & Avedisian School of Medicine

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.

"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 PhD 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.

These findings appear online in the journal Neuroscience of Consciousness.

This work resulted from data collected through NIH (R01 AG060987) and the BrightFocus Foundation (A2021288S). B.H. is a PhD student and R.A.O. and K.X. are research fellows. S.B. is funded in part by NIA (NIH;1K23AG068384), the Alzheimer's Association (2019-AACSF- 643094), and an internal BIDMC SPARK award. P.J.F. is funded in part by BrightFocus (A2021288S). M.M.S. is funded in part by NIH (R01 AG060987, MH115949, EB032820; P01 AG031720). K.W.T. is funded in part by the Veterans Health Administration (IK2CX002065) and NIH/NIA (P30 AG072978). A.E.B. is funded in part by the Veterans Health Administration (I01CX002400) and NIH/NIA (P30 AG072978). B.F. is funded in part by the Veterans Health Administration (IK2CX002625).