Differences in electroencephalography oscillations between normal aging and mild cognitive impairment during semantic memory retrieval.

Semantic memory remains relatively stable with normal cognitive aging and declines in early stages of neurodegenerative disease. We measured electroencephalography (EEG) oscillatory correlates of semantic memory retrieval to examine the effects of normal and pathological aging. Twenty-nine cognitively healthy young adults (YA), 22 cognitively healthy aging adults (HA) and 20 patients with mild cognitive impairment (MCI) completed a semantic memory retrieval task with concurrent EEG recording in which they judged whether two words (features of objects) led to retrieval of an object (retrieval) or not (non-retrieval). Event-related power changes contrasting the two conditions (retrieval vs. non-retrieval) within theta, alpha, low-beta and high-beta EEG frequency bands were examined for normal aging (YA vs. HA) and pathological aging effects (HA vs. MCI). With no behavioural differences between the two normal age groups, we found later theta and alpha event-related power differences between conditions only in YA and a high-beta event-related power difference only in HA. For pathological aging effects, with reduced accuracy in MCI, we found different EEG patterns of early event-related beta power differences between conditions in MCI compared with HA and an event-related low-beta power difference only in HA. Beta oscillations were correlated with behavioural performance only in HA. We conclude that the aging brain relies on faster (beta) oscillations during the semantic memory task. With pathological aging, retrieval accuracy declines and pattern of beta oscillation changes. The findings provide insights about age-related neural mechanisms underlying semantic memory and have implications for early detection of pathological aging.

Enhancing latent cognitive capacity in mild cognitive impairment with gist reasoning training: a pilot study.

OBJECTIVE: Cognitive training offers a promising way to mitigate cognitive deterioration in individuals with mild cognitive impairment (MCI). This randomized control pilot trial examined the effects of Gist Reasoning Training on cognition as compared with a training involving New Learning in a well-characterized MCI group. METHODS: Fifty participants with amnestic MCI were randomly assigned to the experimental Gist Training group or an active control New Learning group. Both groups received 8 h of training over a 4-week period. We compared pre-training with post-training changes in cognitive functions between the two training groups. RESULTS: The Gist Training group showed higher performance in executive function (strategic control and concept abstraction) and memory span compared with the New Learning group. Conversely, the New Learning group showed gains in memory for details. CONCLUSION: These findings suggest that cognitive training in general yields benefits, and more specifically, training programs that target top-down cognitive functions such as gist reasoning may have a broad impact on improving cognition in MCI. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes.

BACKGROUND: West Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that ≤1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future. METHODS: We report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness. RESULTS: At initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition). CONCLUSIONS: This study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00138463 and NCT00069316.

A Critical Review of Noninvasive Brain Stimulation Technologies in Alzheimer's Dementia and Primary Progressive Aphasia.

Multiple pharmacologic agents now have been approved in the United States and other countries as treatment to slow disease and clinical progression for Alzheimer's disease. Given these treatments have not been proven to lessen the cognitive deficits already manifested in the Alzheimer's Clinical Syndrome (ACS), and none are aimed for another debilitating dementia syndrome identified as primary progressive aphasia (PPA), there is an urgent need for new, safe, tolerable, and efficacious treatments to mitigate the cognitive deficits experienced in ACS and PPA. Noninvasive brain stimulation has shown promise for enhancing cognitive functioning, and there has been interest in its potential therapeutic value in ACS and PPA. This review critically examines the evidence of five technologies in ACS and PPA: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), repetitive transcranial magnetic stimulation (rTMS), and noninvasive vagus nerve stimulation (nVNS). Many randomized controlled trials of tDCS and rTMS report positive treatment effects on cognition in ACS and PPA that persist out to at least 8 weeks, whereas there are few trials for tACS and none for tRNS and nVNS. However, most positive trials did not identify clinically meaningful changes, underscoring that clinical efficacy has yet to be established in ACS and PPA. Much is still to be learned about noninvasive brain stimulation in ACS and PPA, and shifting the focus to prioritize clinical significance in addition to statistical significance in trials could yield greater success in understanding its potential cognitive effects and optimal parameters.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart et al., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Traumatic Brain Injury Characteristics Are Not Related to Neurocognitive Decline in Older Adults: A Nationwide Longitudinal Cohort Study.

OBJECTIVE: Evaluate whether traumatic brain injury (TBI) characteristics, age of injury, or recency of injury predicts the course of neurocognitive decline and/or increases conversion rates to mild cognitive impairment (MCI) or dementia. METHODS: Data were obtained from the National Alzheimer's Coordinating Center for participants 50-85 years old with 3-5 visits from 2015 to 2022, with or without TBI history (TBI+ = 508; TBI- = 2,382). Groups were stratified by self-reported TBI history (i.e., single TBI without loss of consciousness [LOC], single TBI with LOC, multiple TBI without LOC, and multiple TBI with LOC), age of most recent TBI, and recency of TBI. Mixed linear models compared neuropsychological composite trajectories (executive functioning/attention/speed, language, memory, and global), co-varying for age, gender, education, apolipoprotein E4 status, race/ethnicity, and baseline diagnosis (normal aging n = 1,720, MCI n = 749, or dementia n = 417). Logistic binary regression examined MCI/dementia conversion rates. RESULTS: There was a slightly higher frequency of MCI/dementia in those with multiple TBIs (50% to 60% with and without LOC, compared to 39% with no TBI) at baseline, but longitudinal trajectories were similar. TBI history, age of injury, or recency of injury did not impact neurocognitive trajectories or conversion rates to MCI/dementia (all p's > .01). CONCLUSIONS: TBI history, regardless of injury characteristics, age of injury, or recency of injury, did not worsen neurocognitive decline or MCI/dementia conversion. Additional longitudinal research in more diverse cohorts with a wider range of TBI severity is needed to evaluate the specific factors and possible mechanisms in which TBI may increase dementia risk.

Verbal retrieval deficits due to traumatic brain injury are associated with changes in event related potentials during a Go-NoGo task.

OBJECTIVE: Verbal retrieval (VR) deficits often occur after traumatic brain injury (TBI), but the mechanisms remain unclear. We examined how event-related potentials (ERPs) during a Go-NoGo task were associated with VR deficits. METHODS: Sixty veterans with a history of TBI underwent a neuropsychological battery and a Go-NoGo task with concurrent EEG recording. We compared task performance and ERP measures (N2, P3) between those with and those without persistent injury-related VR deficits. We then used generalized linear modeling to examine the relationship between ERP measures and scores on measures of executive function and processing speed. RESULTS: Go-NoGo task performance was comparable between the groups. Those with VR deficits had larger N2 amplitude in NoGo than in Go conditions. In participants with VR deficits, larger NoGo N2/P3 amplitude predicted faster processing speed. Furthermore, larger P3 amplitude and shorter P3 latency of the difference wave (NoGo - Go) predicted faster processing speed in those with VR deficits. CONCLUSIONS: Despite no difference in Go-NoGo task performance, ERP amplitude and latency measures associated with cognitive control during Go-NoGo distinguished TBI individuals with VR deficits from those without. SIGNIFICANCE: This study furthers our understanding of VR deficits in TBI and implicates potential application of ERP measures in monitoring and treating such deficits.

Corrigendum: Case report: Improving verbal retrieval deficits with high definition transcranial direct current stimulation targeting the pre-supplementary motor area in a patient with chronic traumatic brain injury.

[This corrects the article DOI: 10.3389/fneur.2021.678518.].

History of traumatic brain injury does not alter course of neurocognitive decline in older adults with and without cognitive impairment.

OBJECTIVE: Traumatic brain injury (TBI) history is associated with dementia risk, but it is unclear whether TBI history significantly hastens neurocognitive decline in older adults. METHOD: Data were derived from the National Alzheimer's Coordinating Center (NACC) data set. Participants with a history of TBI (TBI +; n = 1,467) were matched to individuals without a history of TBI (TBI-; n = 1,467) based on age (50-97, M = 71.61, SD = 8.40), sex, education, race, ethnicity, cognitive diagnosis, functional decline, number of Apolipoprotein ε4 (APOE ε4) alleles, and number of annual visits (3-6). Mixed linear models were used to assess longitudinal neuropsychological test composite scores of executive functioning/attention/speed, language, and memory in TBI + and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined. RESULTS: Longitudinal neuropsychological functioning did not differ between TBI groups (p's > .001). There was a significant three-way interaction (age, TBI history, time) in language (F[20, 5750.1] = 3.133, p < .001) and memory performance (F[20, 6580.8] = 3.386, p < .001), but post hoc analyses revealed TBI history was not driving this relationship (all p's > .096). No significant interactions were observed between TBI history and sex, education, race/ethnicity, number of APOE ε4 alleles, or cognitive diagnosis (p's > .001). CONCLUSIONS: Findings suggest TBI history, regardless of demographic factors, APOE ε4 status, or cognitive diagnosis, does not alter the course of neurocognitive functioning later-in-life in older adults with or without cognitive impairment. Future clinicopathological longitudinal studies that well-characterize head injuries and the associated clinical course are needed to help clarify the mechanism in which TBI may increase dementia risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Microglia as a cellular target of diclofenac therapy in Alzheimer's disease.

Alzheimer's disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit. More recently, protective effects of diclofenac and NSAIDs in the fenamate group have been reported. Diclofenac decreased the frequency of AD significantly compared to other NSAIDs in a large retrospective cohort study. Diclofenac and fenamates share similar chemical structures, and evidence from cell and mouse models suggests that they inhibit the release of pro-inflammatory mediators from microglia with leads to the reduction of AD pathology. Here, we review the potential role of diclofenac and NSAIDs in the fenamate group for targeting AD pathology with a focus on its potential effects on microglia.