%0 Journal Article %J J Alzheimers Dis %D 2021 %T Memory-Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis. %A Jiang, Yang %A Li, Juan %A Schmitt, Frederick A %A Jicha, Gregory A %A Munro, Nancy B %A Zhao, Xiaopeng %A Smith, Charles D %A Kryscio, Richard J %A Abner, Erin L %K Aged %K Brain Waves %K Cognition %K Cognitive Dysfunction %K Electroencephalography %K Female %K Humans %K Longitudinal Studies %K Male %K Memory, Short-Term %K Neuropsychological Tests %K Prodromal Symptoms %X

BACKGROUND: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer's disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals.

OBJECTIVE: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis.

METHODS: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed.

RESULTS: Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters' frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters' baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08).

CONCLUSION: The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.

%B J Alzheimers Dis %V 79 %P 531-541 %8 2021 %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/33337367?dopt=Abstract %R 10.3233/JAD-200931 %0 Journal Article %J J Alzheimers Dis %D 2021 %T Selective Impairment of Long-Range Default Mode Network Functional Connectivity as a Biomarker for Preclinical Alzheimer's Disease in People with Down Syndrome. %A DiProspero, Natalie D %A Keator, David B %A Phelan, Michael %A van Erp, Theo G M %A Doran, Eric %A Powell, David K %A Van Pelt, Kathryn L %A Schmitt, Frederick A %A Head, Elizabeth %A Lott, Ira T %A Yassa, Michael A %X

BACKGROUND: Down syndrome (DS) is associated with increased risk for Alzheimer's disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS.

OBJECTIVE: Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS?

METHODS: Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38-61 years).

RESULTS: Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity.

CONCLUSION: Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.

%B J Alzheimers Dis %V 85 %P 153-165 %8 2022 Jan 04 %G eng %N 1 %R 10.3233/JAD-210572 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Challenges and Considerations Related to Studying Dementia in Blacks/African Americans. %A Ighodaro, Eseosa T %A Nelson, Peter T %A Kukull, Walter A %A Schmitt, Frederick A %A Abner, Erin L %A Caban-Holt, Allison %A Bardach, Shoshana H %A Hord, Derrick C %A Glover, Crystal M %A Jicha, Gregory A %A Van Eldik, Linda J %A Byrd, Alexander X %A Fernander, Anita %X

Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations.

%B J Alzheimers Dis %V 60 %P 1-10 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/28731440?dopt=Abstract %R 10.3233/JAD-170242