11 research outputs found
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The elusive nature of APOE e4 in mid-adulthood: understanding the cognitive profile
Objectives: The apolipoprotein E (APOE) e4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This study undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable. Methods: Thirty-six papers investigating the behavioral effects of APOE e4 in mid-adulthood (defined as a mean sample age between 35 and 60 years) were reviewed. In addition, the effect of carrying an e4 allele on individual cognitive domains was assessed in separate meta-analyses. Results: The average effect size of APOE e4 status was non-significant across cognitive domains. Further consideration of genotype effects indicates preclinical effects of APOE e4 may be observable in memory and executive functioning. Conclusions: The cognitive profile of APOE e4 carriers at mid-age remains elusive. Although there is support for comparable performance by e4 and non-e4 carriers in the 5th decade, studies administering sensitive cognitive paradigms indicate a more nuanced profile of cognitive differences. Methodological issues in this field preclude strong conclusions, which future research must address, as well as considering the influence of further vulnerability factors on genotype effects
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Nicotinic treatment for degenerative neuropsychiatric disorders such as Alzheimerâs disease and Parkinsonâs disease
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Degree of dependence influences the effect of smoking on cognitive flexibility.
Pre-frontal cortical (PFC) dysfunction has been put forward as the basis for development and maintenance of addiction. To explore this relationship, the present study investigated the effects of smoking on PFC-mediated cognitive flexibility and subjective states in low- (LD) and high-dependent (HD) smokers. Twenty-four LD and 24 HD smokers (Fagerström dependence scores = 4 and = 5, respectively) were randomly allocated to non-smoking or smoking condition (12 LD and 12 HD participants per condition). After abstaining from smoking for a minimum of two hours volunteers completed a battery of questionnaires [nicotine-specific Visual Analogue Scales (Nic-VAS), Questionnaire of Smoking Urges (QSU) and Profile of Mood States (POMS)] at baseline [T1] and again after smoking one cigarette or remaining abstinent [T2]. Cognitive flexibility was evaluated at T2 using the Intra-Extra Dimensional Set-Shift test. The Rapid Visual Information Processing test was performed as a control nicotine-sensitive task at several time points during the experiment. Compared to LD smokers, HD smokers had higher salivary cotinine and breath CO levels at baseline and reported more craving (QSU) and felt less stimulated (Nic-VAS), vigorous, friendly and elated (POMS) throughout the experiment. Smoking increased Nic-VAS ratings of 'Buzzed' and 'Dizzy' and decreased craving in all participants. Smoking selectively impaired cognitive flexibility in HD smokers since HD smokers allocated to the smoking condition made significantly more errors with the intra-dimensional set-shift than their counterparts in the abstinent condition. No effect of smoking on RVIP test was observed, most likely due to the practice effect which was significant in both groups of smokers. The practice effect, however, was more pronounced in LD smokers. This study demonstrates that PFC-mediated cognitive effects of smoking as well as subjective reports vary according to the degree of nicotine dependence
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A role for glutamate in subjective response to smoking and its action on inhibitory control
Rationale Our previous study using memantine in smokers suggests that there may be a differential role for N-methyl-d-aspartate (NMDA) receptors in the subjective and cognitive effects of smoking. Objectives This study was designed to investigate if d-cycloserine (DCS) would modulate the subjective and cognitive effects of limited smoking. Methods Forty-eight habitual smokers abstinent for a minimum of 2 h were randomly allocated to receive either placebo or 50 mg DCS (double-blind) and were subsequently required either to smoke half of one cigarette or to remain abstinent. Subjective and physiological effects of DCS were measured at baseline, 90 min postcapsule, and again after the partial-smoking manipulation, while the effects on sustained attention (rapid visual information processing testâRVIP) and cognitive flexibility (intraâextra dimensional set-shift testâIED) were evaluated only after the partial-smoking manipulation. Results DCS alone did not produce significant subjective effects other than an increase in ratings of âStimulatedâ. In combination with partial smoking, however, DCS blocked the smoking-induced increase in âStimulatedâ and the decrease in âRelaxedâ ratings. Furthermore, in combination with smoking, DCS reduced the number of false alarms during the RVIP test (an index of inhibitory control) and produced a small increase in diastolic blood pressure. DCS failed to modulate IED performance. Conclusions These findings provide further evidence of a role for glutamate release in the subjective effects of smoking but not the effects on attention and cognitive flexibility. Furthermore, our results indicate that glutamate release may also be involved in the effect of smoking on inhibitory control
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Effect of varenicline on aspects of inhibitory control in smokers
RATIONALE: Varenicline, a partial agonist at a4Ă2 nicotinic receptors (nAChRs) aids smoking cessation by reducing craving. Successful quitting may be associated with greater inhibitory control but the effectiveness of varenicline in this regard is unknown. OBJECTIVES: This study aimed to investigate the effect of varenicline on aspects of inhibitory control in smokers. METHODS: A double-blind, placebo-controlled study investigating the effect of varenicline 1 mg (or matched placebo) in satiated and abstinent smokers. Tests included Rapid Visual Information Processing (RVIP), Stop-Signal (SS), Prospective Memory (PM) and the Cambridge Gambling Task (CGT). RESULTS: Smoking enhanced RVIP accuracy and latency to respond. Varenicline did not alter RVIP performance, nor the effect of smoking, suggesting that these effects were unrelated to a4Ă2 nAChRs. Smoking increased the number of errors during SS and increased the stop latency, indicating that smoking decreased inhibitory control. Varenicline partially mimicked this effect of smoking but also reduced the smoking-induced increase, indicating a role for a4Ă2 nAChRs. Likewise, smoking increased the number of points bet following a win during CGT and varenicline blocked this effect. There was no effect of smoking or varenicline on PM target detection per se. However, smoking protected the target detection rate in the ongoing task when a concurrent intention was introduced. Varenicline improved response speed in both satiated and abstinent smokers. CONCLUSIONS: Some aspects of inhibitory control may be mediated by a4Ă2-related mechanisms and blockade of smoking-induced disinhibition may contribute towards the action of varenicline as an aid to smoking cessation
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Effects of caffeine on performance and mood depend on the level of caffeine abstinence
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Mid age APOE e4 carriers show memory-related functional differences and disrupted structure-function relationships in hippocampal regions
Carriers of the APOE e4 allele are at higher risk of age-related cognitive decline and Alzheimer's disease (AD). The underlying neural mechanisms are uncertain, but genotype differences in medial temporal lobe (MTL) functional activity and structure at mid-age might contribute. We tested 16 non-e4 and 16 e4 carriers (aged 45-55) on a subsequent memory task in conjunction with MRI to assess how hippocampal volume (from T1 structural) and microstructure (neurite orientation-dispersion, from NODDI) differs by genotype and in relation to memory encoding. No previous study has investigated APOE effects on hippocampal microstructure using NODDI. Recall performance did not differ by genotype. A genotype by condition interaction in left parahippocampus indicated that in e4 carriers activity did not differentiate subsequently remembered from forgotten words. Hippocampal volumes and microstructure also did not differ by genotype but hippocampal volumes correlated positively with recognition performance in non-e4 carriers only. Similarly, greater hippocampal neurite orientation-dispersion was linked to better recall but only in non-e4s. Thus, we suggest that mid-age e4 carriers show a breakdown of normal MTL activation and structure-performance relationships. This could reflect an inability to utilise compensatory mechanisms, and contribute to higher risk of cognitive decline and AD in later life
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Using event-related fMRI to examine sustained attention processes and e?ects of APOE e4 in young adults
In this study we investigated effects of the APOE e4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimerâs Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE e4 allele, and 26 non carriers (aged 18â28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that e4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only e4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in e4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult e4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories
Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers
Introduction: Few studies have longitudinally mapped Quality of Life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during COVID-19.
Methods: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and two years later. Latent growth curve modeling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL).
Results: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic, and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. âConfidence in futureâ and âFeeling supportedâ were the only carer QoL subscales to show some recovery post-pandemic.
Discussion: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL.</p
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Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers
Introduction: Few studies have longitudinally mapped Quality of Life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during COVID-19.
Methods: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and two years later. Latent growth curve modeling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL).
Results: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic, and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. âConfidence in futureâ and âFeeling supportedâ were the only carer QoL subscales to show some recovery post-pandemic.
Discussion: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL.</p