Mild cognitive impairment (MCI) defines the intermediate state between healthy cognition and early dementia1 and is not typical for normal brain aging2. In 2020 the estimated prevalence of MCI in elderlies was 22.7%, and it is projected that the number of people in the US with MCI will almost double by 20603. The associated increasing rate of dementia and the importance of early detection of its forerunners have underlined the importance of detecting MCI for better management of dementia and its consequences. However, the heterogeneity in cognitive deficits, the long presymptomatic phase (See Figure 1), and the fact that not all may only suffer from memory problems 4, make the identification and monitoring of MCI particularly challenging. Current routine examinations like the Mini Mental State Exam (MMSE) have been shown to be insufficient as stand-alone tools in managing MCI and dementia5. Thus, there is a pressing need for new clinical examinations and tools that can track subtle cognitive changes, detect the onset of MCI and register the progression to dementia.
A 77- year-old male with suspected MCI enrolled in a clinical study.
BNA™ was recorded twice in the first week and again after six months. The MMSE score was calculated at each visit, which showed normal cognition at all three visits (See Figure 2).
Summary Report of the Auditory Oddball Task
BNA™ Results & Physician Interpretation
The research physician interpreted the BNA™ results as following:
BNA™ Visit 1: The first visit shows slightly enlarged ERP amplitudes in the N100 (Z-score +1.4) and P200 (Z-score +1.4) and a strongly enlarged P3b amplitude (Z-score +2.4). The N100 and P200 are commonly associated with sensory processing and attention, respectively 6. The P3b has been associated with working memory7. The physician interpreted this higher neural recruitment as compensatory mechanisms that can appear early in degenerative diseases before the relevant amplitudes commonly decline as the disease progresses. Further inspection of the ERP Report showed strongly decreased neural consistencies in the P200 (Z-score -2.0) and P3b (Z-score -2.1). Low neural consistency indicates little reliability in how the brain reacts to the same type of stimulus. Internal elminda studies could correlate such patterns with impacted cognitive functions.
BNA™ Visit 2: The second visit, conducted one week later, showed further increases in the amplitudes of the N100 (Z-score +1.9) and the P200 (Z-score +2.2). The accuracy dropped by 10%. However, the P3b was less enlarged than in the previous visit (Z-score +2.0), and its neural consistency score was closer to the normal range (Z-score -0.9) than before. The physician interpreted these fluctuations within only one week as typical for MCI patients in which “good” and “bad days” alternate8.
BNA™ Visit 3: The last BNA™ visit occurred six months later. The amplitudes of the N100 and P200 continued to increase (Z-scores +2.1 and +2.3, respectively), while the amplitude of the P3b seemed to have normalized (Z-score +0.6). The physician interpreted this additional neural recruitment in the sensory processing and attentional domains (N100 & P200) as a continuation of the brain’s compensation as the neurodegeneration progresses. The reduced P3b was due to the steep drop not interpreted as normalization in electrophysiology or as part of the usual “up and downs” in MCI, but rather as the first indicator of a starting decline in the P3b ‘s amplitude as expected in a progression to Dementia9. The neural consistencies for both the P200 and P3b remained low (Z-scores -2.1 and -1.1, respectively), further indicating instability in brain responses.
Benefits of BNA™ for MCI Detection and Monitoring
Despite the MMSE score remaining on a normal level, the BNA™ scores indicated from the first visit on substantial deviations from the healthy age-matched norm in the domains of sensory processing (N100), attention (P200) and working memory (P3b). The physician interpreted these BNA™ results as indicators of compromised cognitive networks that the MMSE was not sensitive enough to detect at such early stages. Thus, using BNA™ in primary care settings could sensitize standard screenings to detect subtle cognitive changes that may otherwise go unnoticed. The monitoring of results across the three visits further identified variations in neurophysiology that could indicate the first signs of a progression to dementia, making BNA™ a valuable tool for both the screening and monitoring phase in MCO and dementia.
- Reisberg B, Ferris SH, de Leon MJ, et al. Stage-Specific Behavioral, Cognitive, and In Vivo Changes in Community Residing Subjects With Age-Associated Memory Impairment and Primary Degenerative Dementia of the Alzheimer Type. Vol 15.; 1988.
- Snyder PJ, Jackson CE, Petersen RC, et al. Assessment of cognition in mild cognitive impairment: A comparative study. Alzheimer’s and Dementia. 2011;7(3):338-355. doi:10.1016/j.jalz.2011.03.009
- Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020–2060). Alzheimer’s and Dementia. 2021;17(12):1966-1975. doi:10.1002/alz.12362
- Decarli C. Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. THE LANCET Neurology. 2003;2:15-21. http://neurology.thelancet.com
- Arevalo-Rodriguez I, Smailagic N, Roqué-Figuls M, et al. Mini-Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews. 2021;2021(7). doi:10.1002/14651858.CD010783.pub3
- Crowley KE, Colrain IM. A review of the evidence for P2 being an independent component process: age, sleep and modality. Clinical Neurophysiology. 2004;115(4):732-744. doi:10.1016/j.clinph.2003.11.021
- Polich J. Updating P300: An integrative theory of P3a and P3b. Clinical Neurophysiology. 2007;118(10):2128-2148. doi:10.1016/j.clinph.2007.04.019
- Zonderman AB, Dore GA. Risk of dementia after fluctuating mild cognitive impairment : When the yo-yoing stops. Neurology. 2014;82(4):290-291. doi:10.1212/WNL.0000000000000065
- Bonanni L, Franciotti R, Onofrj V, et al. Revisiting P300 cognitive studies for dementia diagnosis: Early dementia with Lewy bodies (DLB) and Alzheimer disease (AD). Neurophysiologie Clinique/Clinical Neurophysiology. 2010;40(5-6):255-265. doi:10.1016/j.neucli.2010.08.001