Kirk Daffner - Academia.edu (original) (raw)
Papers by Kirk Daffner
OBJECTIVE: To investigate the impact of peripheral sensory impairment (visual and auditory) on ag... more OBJECTIVE: To investigate the impact of peripheral sensory impairment (visual and auditory) on age-related differences in the decision-making process, as indexed by the P3b event-related potential (ERP). BACKGROUND: Numerous studies using a variety of functional imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. One of the most commonly observed finding in the ERP literature on cognitive aging is a reduction in posterior P3b amplitude, an index of cognitive decision-making/updating. Surprisingly, little attention has been paid to the potential influence of age-associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had “normal or corrected- to-normal vision.” However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied on self-reported visual status, which is often inaccurate. METHODS: ERP data from a visual oddball task were collected in well-matched young (n = 26) and old adults (n = 29) subjects. Visual acuity (with corrective lenses) was measured with a Snellen 10 feet wall chart. Auditory acuity was measured using an audiogram. Age-related differences in visual P3b were analyzed before and after controlling for visual and auditory deficits. RESULTS: Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neurocognitive processing. CONCLUSION: We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing. Disclosure: Dr. Porto has nothing to disclose. Dr. Tusch has nothing to disclose. Dr. Fox has nothing to disclose. Dr. Alperin has nothing to disclose. Dr. Holcomb has nothing to disclose. Dr. Daffner has nothing to disclose.
Neurology, Apr 6, 2015
Objective: To investigate whether long-term potentiation (LTP) in the visual pathway persists in ... more Objective: To investigate whether long-term potentiation (LTP) in the visual pathway persists in older adults. Background: LTP is a process by which synaptic strength is augmented. It is believed to serve as a critical mechanism underlying learning, memory and neuroplasticity. In-vitro work on LTP has been done on hippocampal slices using high frequency stimulation. However, it has been difficult to demonstrate LTP in vivo. Recently, LTP was reported in young adults by measuring visual evoked potentials (VEPs) before and after tetanic visual stimulation (TVS). Methods: Seventeen healthy adults, 65 years and older, were recruited from the community. Subjects had a mean age of 77.4 yo, mean MMSE of 29.1, and demonstrated normal visual acuity and performance on neuropsychological tests. VEPs in response to 1 Hz alternating checkerboard stimulation to one hemi-field were recorded before and after 2 minutes of TVS at 9Hz to the same hemi-field. The N1 component was measured at occipital electrode sites in the hemisphere contralateral to tetanic stimulation. Results: The amplitude of the N1 component in response to 1 Hz stimulation was larger after TVS than before TVS [-6.6 (6.5) µV vs. -5.7 (6) µV, p = 0.023 (paired t-test)], indicating a reliable increase in N1 amplitude in response to TVS. Conclusions: High frequency visual stimulation can enhance the N1 response in cognitively normal older adults. This finding suggests that LTP in visual pathways may persist into late life. Future studies should compare the magnitude of this effect in young vs. old subjects, and determine the extent to which this marker of neural plasticity is reduced in neurodegenerative disease. Disclosure: Dr. Porto has nothing to disclose. Dr. Fox has nothing to disclose. Dr. Tusch has nothing to disclose. Dr. Sorond has nothing to disclose. Dr. Mohammed has nothing to disclose. Dr. Daffner has nothing to disclose.
Humana Press eBooks, Feb 9, 2000
Journal of Cognitive Neuroscience, Jun 1, 2011
This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms ... more This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms underlying age-and performance-related differences in working memory. Young and old subjects participated in a verbal n-back task with three levels of difficulty. Each group was divided into high and low performers based on accuracy under the 2-back condition. Both old subjects and low-performing young subjects exhibited impairments in preliminary mismatch/ match detection operations (indexed by the anterior N2 component). This may have undermined the quality of information available for the subsequent decision-making process (indexed by the P3 component), necessitating the appropriation of more resources. Additional anterior and right hemisphere activity was recruited by old subjects. Neural efficiency and the capacity to allocate more resources to decision-making differed between high and low performers in both age groups. Under low demand conditions, high performers executed the task utilizing fewer resources than low performers (indexed by the P3 amplitude). As task requirements increased, high-performing young and old subjects were able to appropriate additional resources to decision-making, whereas their low-performing counterparts allocated fewer resources. Higher task demands increased utilization of processing capacity for operations other than decision-making (e.g., sustained attention) that depend upon a shared pool of limited resources. As demands increased, all groups allocated additional resources to the process of sustaining attention (indexed by the posterior slow wave). Demands appeared to have exceeded capacity in low performers, leading to a reduction of resources available to the decision-making process, which likely contributed to a decline in performance.
Alzheimer's & Dementia: Translational Research & Clinical Interventions
IntroductionThe often‐cited mechanism linking brain‐derived neurotrophic factor (BDNF) to cogniti... more IntroductionThe often‐cited mechanism linking brain‐derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF.MethodsA total of 144 heathy older adults completed a 5‐week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre‐ and post‐intervention.ResultsLinear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention‐related improvement in task performance. Regression analyses showed t...
Executive Functions in Health and Disease
Cognitive and behavioral flexibility is a core adaptive function of the executive control system ... more Cognitive and behavioral flexibility is a core adaptive function of the executive control system in the human brain. Executive functions include a set of processes that allow for context-appropriate volitional control in “nonroutine situations.” Goal-directed behavior requires not only an ability to represent a goal and then generate a plausible sequence of actions that must be accomplished to achieve it but also an ability to prioritize goals (represent the relative value of various goals at a given time), initiate a goal-directed process, and maintain goal pursuit in the face of unexpected environmental factors that might otherwise command attention. Too much environmental dependency will result in distractibility, a tendency for tasks to be interrupted, and, ultimately, an inability to complete a complex task sequence aimed toward a particular goal. This can manifest clinically as impulsivity, where the individual quickly shifts tasks in response to a novel stimulus, leaving the prior task sequence incomplete. However, one must also be able to discontinue an activity, switching to a different task when appropriate. An excessively rigid adherence to a predetermined task sequence or a previously valued goal prevents an individual from appropriately responding to changing environmental contingencies. We examine a variety of forms of cognitive, emotional, and behavioral perseveration in neuropsychiatric disease, and explore the various mechanisms believed to account for these phenomena. In many neuropsychiatric illnesses, impairments of flexibility in one form or another account for a significant restriction in the range of reactions, feelings, and self-generated behaviors an individual may exhibit, leading to a breakdown in social and occupational functioning, and in many cases, significant suffering. Perseveration, in its broadest conceptualization, can occur at a variety of levels of organization from simple motor behaviors (i.e., tics), verbal utterances, complex cognitions (i.e., obsessions in obsessive compulsive disorder, perseverative rumination in mood and anxiety disorders, fixed delusions in psychosis), complex behaviors (i.e., compulsions in obsessive compulsive disorder and addiction), and perseveration of affect in mood and anxiety disorders.
Alzheimer's & Dementia, 2021
BackgroundEvidence suggests that engagement in cognitively stimulating activities may reduce risk... more BackgroundEvidence suggests that engagement in cognitively stimulating activities may reduce risk of cognitive deterioration and dementia. Mechanisms underlying these observations remain to be determined. Animal research indicates that brain‐derived neurotrophic factor (BDNF) plays an important role in neural plasticity, neurogenesis, synaptic growth, and cognitive performance. Working under the assumption that augmented BDNF levels benefit brain function, investigations of human subjects have focused on determining whether physical or mental activities can increase BDNF levels. Surprisingly little research has been devoted to linking alterations in BDNF to changes in cognition. This study aimed to determine whether changes in BDNF contribute to the enhancement of cognitive performance after computerized cognitive training (CCT). We have demonstrated that five weeks of CCT emphasizing working memory (WM) was associated with improvement on an untrained test of WM/processing speed, th...
Neurology, 2017
Objective: To determine the impact of mindfulness training on attention to novelty and openness t... more Objective: To determine the impact of mindfulness training on attention to novelty and openness to new experiences among healthy older adults. Background: Engagement by novelty has been associated with successful cognitive aging. We were interested in developing accessible ways to promote increased attention to novelty. Mindfulness training seemed a promising approach, given reports that it can augment awareness and attention. Design/Methods: Thirty-eight healthy older adults (mean age 75) were randomized to either a computer-based mindfulness training program or active control condition, involving 25 sessions (~35 minutes each) over five weeks in their homes. The mindfulness training consisted of guided meditation and mindfulness-in-action tasks. The control condition was the non-adaptive, Cogmed working memory training program, in which level of difficulty remains constant. Pre-and post-intervention ERPs were collected during a visual novelty oddball task where subjects controlled...
The Journal of Neuropsychiatry and Clinical Neurosciences, 2021
Journal of Alzheimer's Disease, 2021
A decade has passed since we published a comprehensive review in this journal addressing the topi... more A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there ...
Alzheimer's & Dementia, 2019
physical activity. We analyzed the relationship between global cognition (Mini Mental Status Exam... more physical activity. We analyzed the relationship between global cognition (Mini Mental Status Examination (MMSE)) and self-reported walking, jogging and aerobic exercise on Modified National Health Interview Survey, ExercisePhysical Activity Questionnaire. Metabolic equivalents (METS) were calculated for walking, jogging/running, and aerobic exercise. Results: Participants were predominantly females (99%) and averaged 67 years in age. A linear regression analysis, using MMSE scores as dependent variable and tested whether walking, jogging/ running or doing aerobic exercise associated with memory. Unadjusted results showed significant difference only in the aerobic group, but not significant after adjusted for age, sex, and gender. When we modeled walking, jogging/running or doing aerobic exercise METS as predictor variables, aerobic exercise was significantly associated with MMSE in the initial unadjusted regression analyzes. This relationship remained significant after discounting the effects of age, sex, and gender. Conclusions: Although self-reported aerobic exercise is associated with better performance on the MMSE test, less than 1% of our AA sample reported performing aerobic exercise, while 30% self-reported walking. We conclude that physical activity is beneficial to performance on cognitive tasks. Larger prospective study is needed to validate our findings in AAs.
Alzheimer's & Dementia, 2019
novel potentially pathogenic gene, ZDHHC21, were identified for the first time. Patients from ped... more novel potentially pathogenic gene, ZDHHC21, were identified for the first time. Patients from pedigrees without PSENs/APP mutations presented later age at onset, less severe cognitive impairment and more APOEε4 allele, compared with those from pedigrees with PSENs/APP mutations. ROC curve indicated that a FAD patient with an AAO under 60 years-old and without APOEε4 allele had more chance to possess a PSENs/APP mutation. Conclusions: The identification of 14 novel missense mutations suggests a genetic heterogeneity may exist in Chinese and other ethnics. Majority of pedigrees do not carry PSENs/APP mutations. In these pedigrees, APOEε4 might play an important role. Other pathogenic genes, as indicated by the finding of the ZDHHC21, were also involved in the development of FAD. However, all these assumptions need more and deeper studies in the future. O3-13-06 THE MS4A GENE CLUSTER IS A KEY MODULATOR OF SOLUBLE TREM2 AND ALZHEIMER DISEASE RISK Carlos Cruchaga, Bruno Benitez, Celeste M. Karch, Laura Piccio, Washington University School of Medicine, St. Louis, MO, USA; Washington University in Saint Louis, Saint Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. Contact e-mail: bbenitez@DOM.wustl.edu
Frontiers in Aging Neuroscience, 2019
Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitiv... more Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitive function in older adults. Inferences about age-or disease-related differences in neural and behavioral responses to novelty are most often based on results from single experimental testing sessions. There has been very limited research on whether such findings represent stable characteristics of populations studied, which is essential if investigators are to determine the result of interventions aimed at promoting exploratory behaviors or draw appropriate conclusions about differences in the processing of novelty across diverse clinical groups. The goal of the current study was to investigate the short-term test-retest reliability of event-related potential (ERP) and behavioral responses to novel stimuli in cognitively normal older adults. ERPs and viewing durations were recorded in 70 healthy older adults participating in a subject-controlled visual novelty oddball task during two sessions occurring 7 weeks apart. Mean midline P3 amplitude and latency, mean midline amplitude during successive 50 ms intervals, temporospatial factors derived from principal component analysis (PCA), and viewing duration in response to novel stimuli were measured during each session. Analysis of variance (ANOVA) revealed no reliable differences in the value of any measurements between Time 1 and 2. Intraclass correlation coefficients (ICCs) between Time 1 and 2 were excellent for mean P3 amplitude (ICC = 0.86), the two temporospatial factors consistent with the P3 components (ICC of 0.88 and 0.76) and viewing duration of novel stimuli (ICC = 0.81). Reliability was only fair for P3 peak latency (ICC = 0.56). Successive 50 ms mean amplitude measures from 100 to 1,000 ms yielded fair to excellent reliabilities, and all but one of the 12 temporospatial factors identified demonstrated ICCs in the good to excellent range. We conclude that older adults demonstrate substantial stability in ERP and behavioral responses to novel visual stimuli over a 7-week period. These results suggest that older adults may have a characteristic way of processing novelty that appears resistant to transient changes in their environment or internal states, which can be indexed during a single testing session. The establishment of reliable measures of novelty processing will allow investigators to determine whether proposed interventions have an impact on this important aspect of behavior.
Alzheimer's & Dementia, 2017
Background:Increased physical activity (PA) is associated with better cognitive function. We inve... more Background:Increased physical activity (PA) is associated with better cognitive function. We investigated whether individuals with memory problems and additional cerebrovascular risk factors (CVD) could increase PA in the short-term and maintain adherence to a PA program in the long-term. We also examined factors influencing PA adherence.Methods:The AIBLActive trial recruited participants with mild cognitive impairment (MCI) or subjective memory complaints (SMC) and at least 1 CVD risk factor from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). They were randomly assigned to a control or PA group. The control group continued their usual PA throughout the study. The PA group was given a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Scheduled group-specific phone calls (n1⁄418) and newsletters (n1⁄417) were administered to both groups over 24 months. The PA group recorded sessions in diaries and adherence was calculated from the number of sessions recorded expressed as the percentage of the sessions prescribed. At baseline, 6, 12 and 24 months participants completed fitness (6-minute walk distance); PA and PA self-efficacy (one’s confidence to be physically active) questionnaires; cognitive and health assessments. Results:The adherence results for the PA group (n1⁄455) comprising of 53% women are reported. At baseline 24% were defined as inactive; men were significantly older than women; 74.7(6SD 5.6) versus 70.1(4.8) years respectively. Five participants did not start the intervention. After 24 months 96% were still in the study. After 6 months mean PA adherence was 83.5% and declined over the trial with mean 24-month adherence being 75.2%. Age, gender andMCI did not significantly influence adherence. Higher baseline self-efficacy (p<0.05) was associated with higher adherence in the first 6months with higher baseline self-efficacy (p<0.05) and fitness (p<0.01) associated with higher 24-month adherence. Positive program enjoyment, helpfulness of the telephone calls and newsletters were reported by 94%; 98% and 93% of participants respectively. Conclusions:The high retention and adherence rates in both the short and long-term demonstrate that this PA program was both achievable and acceptable in this target group.
Journal of Alzheimer's disease : JAD, Jan 2, 2018
Developing effective interventions to attenuate age-related cognitive decline and prevent or dela... more Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used a...
Neurobiology of Aging, 2000
Early Diagnosis of Alzheimer's Disease
modulation of selective attention to features reflect
The Journal of Neuropsychiatry and Clinical Neurosciences
OBJECTIVE: To investigate the impact of peripheral sensory impairment (visual and auditory) on ag... more OBJECTIVE: To investigate the impact of peripheral sensory impairment (visual and auditory) on age-related differences in the decision-making process, as indexed by the P3b event-related potential (ERP). BACKGROUND: Numerous studies using a variety of functional imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. One of the most commonly observed finding in the ERP literature on cognitive aging is a reduction in posterior P3b amplitude, an index of cognitive decision-making/updating. Surprisingly, little attention has been paid to the potential influence of age-associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had “normal or corrected- to-normal vision.” However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied on self-reported visual status, which is often inaccurate. METHODS: ERP data from a visual oddball task were collected in well-matched young (n = 26) and old adults (n = 29) subjects. Visual acuity (with corrective lenses) was measured with a Snellen 10 feet wall chart. Auditory acuity was measured using an audiogram. Age-related differences in visual P3b were analyzed before and after controlling for visual and auditory deficits. RESULTS: Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neurocognitive processing. CONCLUSION: We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing. Disclosure: Dr. Porto has nothing to disclose. Dr. Tusch has nothing to disclose. Dr. Fox has nothing to disclose. Dr. Alperin has nothing to disclose. Dr. Holcomb has nothing to disclose. Dr. Daffner has nothing to disclose.
Neurology, Apr 6, 2015
Objective: To investigate whether long-term potentiation (LTP) in the visual pathway persists in ... more Objective: To investigate whether long-term potentiation (LTP) in the visual pathway persists in older adults. Background: LTP is a process by which synaptic strength is augmented. It is believed to serve as a critical mechanism underlying learning, memory and neuroplasticity. In-vitro work on LTP has been done on hippocampal slices using high frequency stimulation. However, it has been difficult to demonstrate LTP in vivo. Recently, LTP was reported in young adults by measuring visual evoked potentials (VEPs) before and after tetanic visual stimulation (TVS). Methods: Seventeen healthy adults, 65 years and older, were recruited from the community. Subjects had a mean age of 77.4 yo, mean MMSE of 29.1, and demonstrated normal visual acuity and performance on neuropsychological tests. VEPs in response to 1 Hz alternating checkerboard stimulation to one hemi-field were recorded before and after 2 minutes of TVS at 9Hz to the same hemi-field. The N1 component was measured at occipital electrode sites in the hemisphere contralateral to tetanic stimulation. Results: The amplitude of the N1 component in response to 1 Hz stimulation was larger after TVS than before TVS [-6.6 (6.5) µV vs. -5.7 (6) µV, p = 0.023 (paired t-test)], indicating a reliable increase in N1 amplitude in response to TVS. Conclusions: High frequency visual stimulation can enhance the N1 response in cognitively normal older adults. This finding suggests that LTP in visual pathways may persist into late life. Future studies should compare the magnitude of this effect in young vs. old subjects, and determine the extent to which this marker of neural plasticity is reduced in neurodegenerative disease. Disclosure: Dr. Porto has nothing to disclose. Dr. Fox has nothing to disclose. Dr. Tusch has nothing to disclose. Dr. Sorond has nothing to disclose. Dr. Mohammed has nothing to disclose. Dr. Daffner has nothing to disclose.
Humana Press eBooks, Feb 9, 2000
Journal of Cognitive Neuroscience, Jun 1, 2011
This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms ... more This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms underlying age-and performance-related differences in working memory. Young and old subjects participated in a verbal n-back task with three levels of difficulty. Each group was divided into high and low performers based on accuracy under the 2-back condition. Both old subjects and low-performing young subjects exhibited impairments in preliminary mismatch/ match detection operations (indexed by the anterior N2 component). This may have undermined the quality of information available for the subsequent decision-making process (indexed by the P3 component), necessitating the appropriation of more resources. Additional anterior and right hemisphere activity was recruited by old subjects. Neural efficiency and the capacity to allocate more resources to decision-making differed between high and low performers in both age groups. Under low demand conditions, high performers executed the task utilizing fewer resources than low performers (indexed by the P3 amplitude). As task requirements increased, high-performing young and old subjects were able to appropriate additional resources to decision-making, whereas their low-performing counterparts allocated fewer resources. Higher task demands increased utilization of processing capacity for operations other than decision-making (e.g., sustained attention) that depend upon a shared pool of limited resources. As demands increased, all groups allocated additional resources to the process of sustaining attention (indexed by the posterior slow wave). Demands appeared to have exceeded capacity in low performers, leading to a reduction of resources available to the decision-making process, which likely contributed to a decline in performance.
Alzheimer's & Dementia: Translational Research & Clinical Interventions
IntroductionThe often‐cited mechanism linking brain‐derived neurotrophic factor (BDNF) to cogniti... more IntroductionThe often‐cited mechanism linking brain‐derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF.MethodsA total of 144 heathy older adults completed a 5‐week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre‐ and post‐intervention.ResultsLinear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention‐related improvement in task performance. Regression analyses showed t...
Executive Functions in Health and Disease
Cognitive and behavioral flexibility is a core adaptive function of the executive control system ... more Cognitive and behavioral flexibility is a core adaptive function of the executive control system in the human brain. Executive functions include a set of processes that allow for context-appropriate volitional control in “nonroutine situations.” Goal-directed behavior requires not only an ability to represent a goal and then generate a plausible sequence of actions that must be accomplished to achieve it but also an ability to prioritize goals (represent the relative value of various goals at a given time), initiate a goal-directed process, and maintain goal pursuit in the face of unexpected environmental factors that might otherwise command attention. Too much environmental dependency will result in distractibility, a tendency for tasks to be interrupted, and, ultimately, an inability to complete a complex task sequence aimed toward a particular goal. This can manifest clinically as impulsivity, where the individual quickly shifts tasks in response to a novel stimulus, leaving the prior task sequence incomplete. However, one must also be able to discontinue an activity, switching to a different task when appropriate. An excessively rigid adherence to a predetermined task sequence or a previously valued goal prevents an individual from appropriately responding to changing environmental contingencies. We examine a variety of forms of cognitive, emotional, and behavioral perseveration in neuropsychiatric disease, and explore the various mechanisms believed to account for these phenomena. In many neuropsychiatric illnesses, impairments of flexibility in one form or another account for a significant restriction in the range of reactions, feelings, and self-generated behaviors an individual may exhibit, leading to a breakdown in social and occupational functioning, and in many cases, significant suffering. Perseveration, in its broadest conceptualization, can occur at a variety of levels of organization from simple motor behaviors (i.e., tics), verbal utterances, complex cognitions (i.e., obsessions in obsessive compulsive disorder, perseverative rumination in mood and anxiety disorders, fixed delusions in psychosis), complex behaviors (i.e., compulsions in obsessive compulsive disorder and addiction), and perseveration of affect in mood and anxiety disorders.
Alzheimer's & Dementia, 2021
BackgroundEvidence suggests that engagement in cognitively stimulating activities may reduce risk... more BackgroundEvidence suggests that engagement in cognitively stimulating activities may reduce risk of cognitive deterioration and dementia. Mechanisms underlying these observations remain to be determined. Animal research indicates that brain‐derived neurotrophic factor (BDNF) plays an important role in neural plasticity, neurogenesis, synaptic growth, and cognitive performance. Working under the assumption that augmented BDNF levels benefit brain function, investigations of human subjects have focused on determining whether physical or mental activities can increase BDNF levels. Surprisingly little research has been devoted to linking alterations in BDNF to changes in cognition. This study aimed to determine whether changes in BDNF contribute to the enhancement of cognitive performance after computerized cognitive training (CCT). We have demonstrated that five weeks of CCT emphasizing working memory (WM) was associated with improvement on an untrained test of WM/processing speed, th...
Neurology, 2017
Objective: To determine the impact of mindfulness training on attention to novelty and openness t... more Objective: To determine the impact of mindfulness training on attention to novelty and openness to new experiences among healthy older adults. Background: Engagement by novelty has been associated with successful cognitive aging. We were interested in developing accessible ways to promote increased attention to novelty. Mindfulness training seemed a promising approach, given reports that it can augment awareness and attention. Design/Methods: Thirty-eight healthy older adults (mean age 75) were randomized to either a computer-based mindfulness training program or active control condition, involving 25 sessions (~35 minutes each) over five weeks in their homes. The mindfulness training consisted of guided meditation and mindfulness-in-action tasks. The control condition was the non-adaptive, Cogmed working memory training program, in which level of difficulty remains constant. Pre-and post-intervention ERPs were collected during a visual novelty oddball task where subjects controlled...
The Journal of Neuropsychiatry and Clinical Neurosciences, 2021
Journal of Alzheimer's Disease, 2021
A decade has passed since we published a comprehensive review in this journal addressing the topi... more A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there ...
Alzheimer's & Dementia, 2019
physical activity. We analyzed the relationship between global cognition (Mini Mental Status Exam... more physical activity. We analyzed the relationship between global cognition (Mini Mental Status Examination (MMSE)) and self-reported walking, jogging and aerobic exercise on Modified National Health Interview Survey, ExercisePhysical Activity Questionnaire. Metabolic equivalents (METS) were calculated for walking, jogging/running, and aerobic exercise. Results: Participants were predominantly females (99%) and averaged 67 years in age. A linear regression analysis, using MMSE scores as dependent variable and tested whether walking, jogging/ running or doing aerobic exercise associated with memory. Unadjusted results showed significant difference only in the aerobic group, but not significant after adjusted for age, sex, and gender. When we modeled walking, jogging/running or doing aerobic exercise METS as predictor variables, aerobic exercise was significantly associated with MMSE in the initial unadjusted regression analyzes. This relationship remained significant after discounting the effects of age, sex, and gender. Conclusions: Although self-reported aerobic exercise is associated with better performance on the MMSE test, less than 1% of our AA sample reported performing aerobic exercise, while 30% self-reported walking. We conclude that physical activity is beneficial to performance on cognitive tasks. Larger prospective study is needed to validate our findings in AAs.
Alzheimer's & Dementia, 2019
novel potentially pathogenic gene, ZDHHC21, were identified for the first time. Patients from ped... more novel potentially pathogenic gene, ZDHHC21, were identified for the first time. Patients from pedigrees without PSENs/APP mutations presented later age at onset, less severe cognitive impairment and more APOEε4 allele, compared with those from pedigrees with PSENs/APP mutations. ROC curve indicated that a FAD patient with an AAO under 60 years-old and without APOEε4 allele had more chance to possess a PSENs/APP mutation. Conclusions: The identification of 14 novel missense mutations suggests a genetic heterogeneity may exist in Chinese and other ethnics. Majority of pedigrees do not carry PSENs/APP mutations. In these pedigrees, APOEε4 might play an important role. Other pathogenic genes, as indicated by the finding of the ZDHHC21, were also involved in the development of FAD. However, all these assumptions need more and deeper studies in the future. O3-13-06 THE MS4A GENE CLUSTER IS A KEY MODULATOR OF SOLUBLE TREM2 AND ALZHEIMER DISEASE RISK Carlos Cruchaga, Bruno Benitez, Celeste M. Karch, Laura Piccio, Washington University School of Medicine, St. Louis, MO, USA; Washington University in Saint Louis, Saint Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. Contact e-mail: bbenitez@DOM.wustl.edu
Frontiers in Aging Neuroscience, 2019
Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitiv... more Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitive function in older adults. Inferences about age-or disease-related differences in neural and behavioral responses to novelty are most often based on results from single experimental testing sessions. There has been very limited research on whether such findings represent stable characteristics of populations studied, which is essential if investigators are to determine the result of interventions aimed at promoting exploratory behaviors or draw appropriate conclusions about differences in the processing of novelty across diverse clinical groups. The goal of the current study was to investigate the short-term test-retest reliability of event-related potential (ERP) and behavioral responses to novel stimuli in cognitively normal older adults. ERPs and viewing durations were recorded in 70 healthy older adults participating in a subject-controlled visual novelty oddball task during two sessions occurring 7 weeks apart. Mean midline P3 amplitude and latency, mean midline amplitude during successive 50 ms intervals, temporospatial factors derived from principal component analysis (PCA), and viewing duration in response to novel stimuli were measured during each session. Analysis of variance (ANOVA) revealed no reliable differences in the value of any measurements between Time 1 and 2. Intraclass correlation coefficients (ICCs) between Time 1 and 2 were excellent for mean P3 amplitude (ICC = 0.86), the two temporospatial factors consistent with the P3 components (ICC of 0.88 and 0.76) and viewing duration of novel stimuli (ICC = 0.81). Reliability was only fair for P3 peak latency (ICC = 0.56). Successive 50 ms mean amplitude measures from 100 to 1,000 ms yielded fair to excellent reliabilities, and all but one of the 12 temporospatial factors identified demonstrated ICCs in the good to excellent range. We conclude that older adults demonstrate substantial stability in ERP and behavioral responses to novel visual stimuli over a 7-week period. These results suggest that older adults may have a characteristic way of processing novelty that appears resistant to transient changes in their environment or internal states, which can be indexed during a single testing session. The establishment of reliable measures of novelty processing will allow investigators to determine whether proposed interventions have an impact on this important aspect of behavior.
Alzheimer's & Dementia, 2017
Background:Increased physical activity (PA) is associated with better cognitive function. We inve... more Background:Increased physical activity (PA) is associated with better cognitive function. We investigated whether individuals with memory problems and additional cerebrovascular risk factors (CVD) could increase PA in the short-term and maintain adherence to a PA program in the long-term. We also examined factors influencing PA adherence.Methods:The AIBLActive trial recruited participants with mild cognitive impairment (MCI) or subjective memory complaints (SMC) and at least 1 CVD risk factor from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). They were randomly assigned to a control or PA group. The control group continued their usual PA throughout the study. The PA group was given a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Scheduled group-specific phone calls (n1⁄418) and newsletters (n1⁄417) were administered to both groups over 24 months. The PA group recorded sessions in diaries and adherence was calculated from the number of sessions recorded expressed as the percentage of the sessions prescribed. At baseline, 6, 12 and 24 months participants completed fitness (6-minute walk distance); PA and PA self-efficacy (one’s confidence to be physically active) questionnaires; cognitive and health assessments. Results:The adherence results for the PA group (n1⁄455) comprising of 53% women are reported. At baseline 24% were defined as inactive; men were significantly older than women; 74.7(6SD 5.6) versus 70.1(4.8) years respectively. Five participants did not start the intervention. After 24 months 96% were still in the study. After 6 months mean PA adherence was 83.5% and declined over the trial with mean 24-month adherence being 75.2%. Age, gender andMCI did not significantly influence adherence. Higher baseline self-efficacy (p<0.05) was associated with higher adherence in the first 6months with higher baseline self-efficacy (p<0.05) and fitness (p<0.01) associated with higher 24-month adherence. Positive program enjoyment, helpfulness of the telephone calls and newsletters were reported by 94%; 98% and 93% of participants respectively. Conclusions:The high retention and adherence rates in both the short and long-term demonstrate that this PA program was both achievable and acceptable in this target group.
Journal of Alzheimer's disease : JAD, Jan 2, 2018
Developing effective interventions to attenuate age-related cognitive decline and prevent or dela... more Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used a...
Neurobiology of Aging, 2000
Early Diagnosis of Alzheimer's Disease
modulation of selective attention to features reflect
The Journal of Neuropsychiatry and Clinical Neurosciences