Biomedical subjects

Linda K McEvoy

Publications and source records attributed to Linda K McEvoy.

6 recordsLinked to original sources

PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗

PubMed2006

Characterizing impaired functional alertness from diphenhydramine in the elderly with performance and neurophysiologic measures.

STUDY OBJECTIVES: Psychometric task performance measures can be highly sensitive to manipulations that impair functional alertness in young adults; such measures have been shown to be less sensitive to reduced alertness in older adults. The purpose of this study is to determine whether neurophysiologic measures can aid in the detection and characterization of impairments in functional alertness in the elderly. DESIGN: Double-blind, placebo-controlled, counter-balanced, crossover study. SETTING: Research laboratory. PARTICIPANTS: Twelve healthy older adults (62-75 years of age). INTERVENTIONS: Diphenhydramine, 50 mg. MEASUREMENTS AND RESULTS: Behavioral performance and electroencephalogram measures were obtained while participants completed spatial working memory and word recognition episodic memory tasks in a baseline interval before drug ingestion and in 4 hourly test intervals following drug ingestion. Relative to placebo, diphenhydramine had marginal effects on task performance yet was effective in reducing alertness, as evidenced by subjective ratings and objective neurophysiologic (electroencephalogram) markers. Diphenhydramine significantly reduced the amplitude of alertness-sensitive event-related potentials recorded during working memory task performance, including the N160 and P300. It also affected neurophysiologic processes underlying episodic memory, as evidenced by a reduction in the difference in event-related potentials between old and new words in the word recognition task. Discriminant analyses incorporating neurophysiologic measures showed that the time course of the central effects of diphenhydramine in older subjects was similar to that previously observed in young adults. CONCLUSIONS: These results demonstrate that diphenhydramine has adverse neurocognitive effects in elderly individuals and highlights the utility of incorporating direct measures of brain function into assessments of functional alertness.

Aged↗

PubMed2006

Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate.

PURPOSE: To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task-related and resting-state EEG and evoked potential (EP) measures. METHODS: We used a double-blind, randomized, crossover design. Healthy adults (N = 29) had two 8-week periods of dose escalation, 4 weeks of drug maintenance (300 mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM) tasks and resting conditions at baseline, at the end of each maintenance phase, and after final washout. RESULTS. LTG did not affect overt performance on the tasks, although it reduced EEG power in both resting and WM task conditions, most prominently in the 6- to 12-Hz frequency range, and attenuated P300 evoked-potential amplitude equally in both WM task loads. TPM slowed responses and increased errors. It also increased EEG power below 6 Hz in all conditions, and reduced the amplitude of a slow wave observed in a difficult version of the WM task. CONCLUSIONS: The drugs produced both task-independent and task-related alterations in neurophysiologic measures. The EEG and EP changes produced by TPM are consistent with an impairment of WM, as evidenced by overt performance deficits on the behavioral tasks. By contrast, the reduction in synchronous cortical activity produced by LTG was not accompanied by cognitive impairment. It is unknown whether such effects would also be observed at lower doses, such as those that often are used in monotherapy for newly diagnosed patients.

Adult↗

PubMed2002

The impact of moderate sleep loss on neurophysiologic signals during working-memory task performance.

STUDY OBJECTIVES: This study examined how sleep loss affects neurophysiologic signals related to attention and working memory. DESIGN: Subjective sleepiness, resting-state electroencephalogram, and behavior and electroencephalogram during performance of working-memory tasks were recorded in a within-subject, repeated-measures design. SETTING: Data collection occurred in a computerized laboratory setting. PARTICIPANTS: Sixteen healthy adults (mean age, 26 years; 8 female) INTERVENTIONS: Data from alert daytime baseline tests were compared with data from tests during a late-night, extended-wakefulness session that spanned up to 21 hours of sleep deprivation. MEASUREMENTS AND RESULTS: Alertness measured both subjectively and electrophysiologically decreased monotonically with increasing sleep deprivation. A lack of alertness-related changes in electroencephalographic measures of the overall mental effort exerted during task execution indicated that participants attempted to maintain high levels of performance throughout the late-night tests. Despite such continued effort, responses became slower, more variable, and more error prone within 1 hour after participants' normal time of sleep onset. This behavior failure was accompanied by significant degradation of event-related brain potentials related to the transient focusing of attention. CONCLUSIONS: Moderate sleep loss compromises the function of neural circuits critical to subsecond attention allocation during working-memory tasks, even when an effort is made to maintain wakefulness and performance. Multivariate analyses indicate that combinations of working-memory-related behavior and neurophysiologic measures can be sensitive enough to permit reliable detection of such effects of sleep loss in individuals. Similar methods might prove useful for assessment of functional alertness in patients with sleep disorders.

Adult↗

PubMed2002

Tracking the cognitive pharmacodynamics of psychoactive substances with combinations of behavioral and neurophysiological measures.

Many common pharmacological treatments have effects on cognitive ability. Psychometric task batteries used to characterize such effects do not provide direct information about treatment-related changes in brain function. Since overt task performance reflects motivation and effort as well as ability, behavioral measures alone may overestimate or underestimate the impact of a pharmacological intervention on brain function. Here we present a method that combines behavioral and neurophysiological measures in an attempt to detect the psychoactive effects of pharmacological treatments with greater sensitivity than that provided by behavioral measures alone. Initial application of the method is made to the data from a double blind, placebo-controlled, crossover study in which caffeine, diphenhydramine, and alcohol were used to alter the mental state of 16 healthy subjects at rest and while they performed low load and high load versions of a working memory task. For each intervention, more sensitive detection of drug or alcohol effects over a four hour period was obtained when EEG variables were included in multivariate analyses than when only behavioral variables were used. These initial results suggest that it can be useful to incorporate neurophysiological measures of brain activity into inferences concerning the acute impact of drugs on mental function, and demonstrate the feasibility of using multivariate combinations of behavioral and neurophysiological measures to sensitively characterize the pharmacodynamics of drug-induced changes in cognition.

Adult↗

PubMed2002

Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin.

OBJECTIVES: The acute effects of a single, low dose of phenytoin on behavioral and neurophysiological measures of cognitive function were examined in healthy adults. METHODS: Electroencephalograms (EEGs) were recorded from 7 healthy volunteers while they performed spatial working memory tasks and while they rested quietly. Behavioral measures, EEG power spectra, and event-related potentials (ERPs) were compared between separate sessions in which subjects ingested either 10mg/kg of phenytoin or placebo. RESULTS: Peak serum levels of phenytoin were in the low therapeutic range. Although participants reported subjective effects of the drug, task accuracy and response time were not affected. In the resting EEG, phenytoin decreased power in the alpha band. In the task-related EEG, the frontal midline theta signal was enhanced in response to increased task difficulty following placebo but not following phenytoin. An attention-related augmentation of the N160 ERP to matching stimuli was also reduced by phenytoin. CONCLUSIONS: Neurophysiological measures displayed sensitivity to subtle alterations in attentional processing even in response to a dose of phenytoin too low to produce behavioral impairment. Such results indicate that EEG and ERP measures can provide information about the neurocognitive side effects of medications that cannot be inferred from cognitive task performance measures alone.

Adult↗