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The Rey 15-item Test is a public-domain, memory-based performance validity test, frequently used in clinical settings. Various efforts have been made to modify the test to make it more sensitive and more robust to effects of lower education and intelligence. The most promising of these is the addition of a recognition trial to the existing free recall paradigm.The present study explored the use of the Rey-15 + Recognition Trial in a sample of 155 younger U.S. military veterans seen for evaluation of mild traumatic brain injury or attention deficit hyperactivity disorder (50 cases classified as invalid, 105 classified as valid).Optimal classification accuracy was obtained on the Combination index (cutoff ≤23, sensitivity = 50%, specificity = 95%) and the Recognition Hits score (cutoff ≤11, sensitivity = 52%, specificity = 93%). The Free Recall score had somewhat lower sensitivity when a similar 95% specificity threshold was set (cutoff ≤11, 38% sensitivity). A qualitative error score used in previous studies did not improve classification accuracy.The Rey-15 + Recognition Trial proved to be effective, with particular advantage bestowed by the recognition trial. Implications of these findings in the context of the study's clinical sample of military veterans and in the broader literature are discussed.

We investigated the imagination inflation effect in healthy older adults and older adults with mild cognitive impairment (MCI) to determine whether an intervention can reduce susceptibility to these distortions, with implications for daily functioning.Fifty-seven older adults aged 69-90 participated. In Session 1, participants either: listened to an action statement being read, performed the action, or imagined performing the action. Actions were eitherMemory was worse for functional compared to nonfunctional actions. For older adults with MCI, the intervention increased correct identifications of functional actions that were performed. For healthy older adults, the intervention increased source memory of functional actions that were imagined. The intervention did not impact the accuracy of nonfunctional actions or the rates of misremembering an action as having been performed.These initial findings supported the efficacy of a cue-utilization intervention to improve memory for functional actions in an imagination inflation effect paradigm in community-dwelling older adults. The use of such strategies represents an important first step in designing interventions that are applicable to daily life. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Post-9/11 service members may return from military service with a complicated set of symptoms and conditions, such as posttraumatic stress disorder (PTSD), depression, substance misuse, and traumatic brain injury (TBI), that interfere with reintegration and impair functioning. Although evidence-based treatments that facilitate recovery exist, their successful delivery at a sufficient dose is limited. Barriers to accessing treatment combined with challenges compiling a comprehensive treatment team further delay delivery of effective evidence-based care for PTSD, TBI, and co-occurring mental health conditions. This paper describes the development of a comprehensive, multidisciplinary, 2-week intensive day program for post-9/11 veterans with complex mental health concerns. The treatment program combines skill building groups, family education, and integrative health approaches with evidence-based individual PTSD or TBI care. Initial results from the first 132 participants were notable for a 97% completion rate, as well as statistically significant and clinically meaningful reductions in PTSD, neurobehavioral, and depression symptom severity for the 107 veterans who completed the PTSD track and the 21 who completed the TBI track. These data suggest the intensive program approach is an effective, well-tolerated model of treatment for post-9/11 veterans with PTSD and/or TBI. Future controlled studies should examine the effectiveness of this intensive model compared to standard evidence-based therapy delivery, as well as longitudinal outcomes.

Background and objectives: To understand the perceptions, knowledge, and understanding of memory, cognition, and aging among older veterans. Research design and methods: Twelve male, Caucasian, community-dwelling veterans from a suburban New England demographic area, aged 62 to 83 years, participated in qualitative interviews. The interviews were audio recorded, transcribed verbatim, and subsequently coded by three independent reviewers. The responses were calculated and analyzed for major themes. Results: Veterans equated healthy aging to be both of a physical and cognitive nature, although a significant subset viewed especially intact cognitive faculties to be a sign of successful aging despite physical limitations. Two of the most widely cited concerns about aging were loss of functional independence and the progression of cognitive decline into dementia, although most of the participants were unable to accurately describe dementia or Alzheimer’s disease. Military service was associated with both positive (e.g., social support) and negative (e.g., trauma) associations with aging. Most of the participants noted the importance of a healthy diet and exercise in aging but were unable to accurately describe a healthy diet or exercise regimen or the effect of these activities on the brain. Discussion and implications: Aging veterans represent a unique population among older adults, and more information is required to understand their specific needs. Older male veterans are less likely to engage in healthcare; for some, education alone may be enough to improve engagement, whereas for others an estimate of current cognitive function would provide the extra motivation required.

This study examined whether objectively measured pretreatment cognitive impairment predicted worse response to treatment for posttraumatic stress disorder. Participants were 113 veterans and active duty service members who participated in a new multidisciplinary 2-week intensive clinical program that included individual trauma-focused cognitive-behavioral therapy, group psychotherapy, psychoeducation, skills-building groups, and complementary and alternative medicine treatments (mean age: 39.7 years [SD=8.5]; 20% women).Prior to treatment, participants completed a brief computerized cognitive battery (CNS Vital Signs) and were operationalized as having cognitive impairment if they scored in the ≤5th percentile on two or more of five core cognitive domains. Participants completed measures of traumatic stress, depression, cognitive self-efficacy, and satisfaction with their ability to participate in social roles before and after treatment.There were no significant correlations between pretreatment individual cognitive test scores and change in the clinical outcome measures. One-half of the study sample (49.6%) met criteria for cognitive impairment. In a mixed multivariate analysis of variance, the interaction between cognitive impairment and time was not significant (F=0.83, df=4, 108, p=0.51), indicating that the pre- to posttreatment changes in outcome scores were not significantly different for the cognitively impaired group compared with the cognitively intact group. The multivariate main effect for time was significant (F=36.75, df=4, 108, p0.001). Follow-up univariate tests revealed significant improvement in traumatic stress, depression, cognitive self-efficacy, and satisfaction with social roles after treatment.Cognitive impairment was not associated with worse response to treatment in veterans with severe and complex mental health problems. Veterans with and without cognitive impairment reported large improvements in symptoms and functioning after treatment.

We conducted a randomized controlled trial of the Aging Well through Interaction and Scientific Education (AgeWISE) program, a 12-week manualized cognitive rehabilitation program designed to provide psychoeducation to older adults about the aging brain, lifestyle factors associated with successful brain aging, and strategies to compensate for age related cognitive decline.Forty-nine cognitively intact participants ≥ 60 years old were randomly assigned to the AgeWISE program (n = 25) or a no-treatment control group (n = 24). Questionnaire data were collected prior to group assignment and post intervention. Two-factor repeated-measures analyses of covariance (ANCOVAs) were used to compare group outcomes.Upon completion, participants in the AgeWISE program reported increases in memory contentment and their sense of control in improving memory; no significant changes were observed in the control group. Surprisingly, participation in the group was not associated with significant changes in knowledge of memory aging, perception of memory ability, or greater use of strategies.The AgeWISE program was successfully implemented and increased participants' memory contentment and their sense of control in improving memory in advancing age.This study supports the use of AgeWISE to improve perspectives on healthy cognitive aging.

While recognition memory has been the primary tool for the assessment of performance validity in neuropsychological evaluations, some consideration has also been given to embedded measures from other cognitive domains, including processing speed. The present study evaluated the classification accuracy of several speed-based measures in a Veterans Affairs Medical Center Polytrauma sample.The present sample consisted of 114 military veterans (Mean age = 35.5, SD = 9.4) referred for a suspected history of mild traumatic brain injury who were administered a full neuropsychological protocol that included several validity checks. Veterans were assigned to Valid (n = 80) or Invalid (n = 34) groups based on outcomes of performance validity measures (PVMs).Several processing speed measures yielded acceptable or excellent classification accuracy; sensitivity values ranged from 29 to 53% with specificity values above 90%. Efforts to identify an improved algorithm that would collapse across multiple processing speed PVMs were unsuccessful compared to classification based on single measures.Processing speed measures can serve as efficient performance validity assessment tools.

Narcolepsy is caused by a loss of orexin/hypocretin signaling, resulting in chronic sleepiness, fragmented non-rapid eye movement sleep, and cataplexy. To identify the neuronal circuits underlying narcolepsy, we produced a mouse model in which a loxP-flanked gene cassette disrupts production of the orexin receptor type 2 (OX2R; also known as HCRTR2), but normal OX2R expression can be restored by Cre recombinase. Mice lacking OX2R signaling had poor maintenance of wakefulness indicative of sleepiness and fragmented sleep and lacked any electrophysiological response to orexin-A in the wake-promoting neurons of the tuberomammillary nucleus. These defects were completely recovered by crossing them with mice that express Cre in the female germline, thus globally deleting the transcription-disrupter cassette. Then, by using an adeno-associated viral vector coding for Cre recombinase, we found that focal restoration of OX2R in neurons of the tuberomammillary nucleus and adjacent parts of the posterior hypothalamus completely rescued the sleepiness of these mice, but their fragmented sleep was unimproved. These observations demonstrate that the tuberomammillary region plays an essential role in the wake-promoting effects of orexins, but orexins must stabilize sleep through other targets.

Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad libitum regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 h after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy.

STUDY OBJECTIVES Narcolepsy is caused by selective loss of the orexin/hypocretin-producing neurons of the hypothalamus. For patients with narcolepsy, chronic sleepiness is often the most disabling symptom, but current therapies rarely normalize alertness and do not address the underlying orexin deficiency. We hypothesized that the sleepiness of narcolepsy would substantially improve if orexin signaling were restored in specific brain regions at appropriate times of day. DESIGN We used gene therapy to restore orexin signaling in a mouse model of narcolepsy. In these Atx mice, expression of a toxic protein (ataxin-3) selectively kills the orexin neurons. INTERVENTIONS To induce ectopic expression of the orexin neuropeptides, we microinjected an adeno-associated viral vector coding for prepro-orexin plus a red fluorescence protein (AAV-orexin) into the mediobasal hypothalamus of Atx and wild-type mice. Control mice received an AAV coding only for red fluorescence protein. Two weeks later, we recorded sleep/wake behavior, locomotor activity, and body temperature and examined the patterns of orexin expression. MEASUREMENTS AND RESULTS Atx mice rescued with AAV-orexin produced long bouts of wakefulness and had a normal diurnal pattern of arousal, with the longest bouts of wake and the highest amounts of locomotor activity in the first hours of the night. In addition, AAV-orexin improved the timing of rapid eye movement sleep and the consolidation of nonrapid eye movement sleep in Atx mice. CONCLUSIONS These substantial improvements in sleepiness and other symptoms of narcolepsy demonstrate the effectiveness of orexin gene therapy in a mouse model of narcolepsy. Additional work is needed to optimize this approach, but in time, AAV-orexin could become a useful therapeutic option for patients with narcolepsy.

Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson’s disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI.

MANY RESEARCHERS HAVE HYPOTHESIZED THAT THE POORLY CONSOLIDATED WAKE AND INAPPROPRIATELY TIMED RAPID EYE MOVEMENT (REM) SLEEP of narcolepsy could be caused by disruption of the circadian rhythms of sleep and wakefulness.1–4 The suprachiasmatic nucleus (SCN) is essential for the timing and consolidation of sleep and wakefulness;5 and squirrel monkeys with SCN lesions lose the circadian rhythms of sleep and wakefulness and are unable to produce long bouts of wakefulness.6 Similarly, people with narcolepsy have difficulty maintaining wakefulness, and their naps often include bouts of REM sleep, regardless of the time of day.1 Most likely, this is not caused by a primary defect in the generation of circadian rhythms because the daily rhythms of body temperature and cortisol are essentially normal.7 Instead, people with narcolepsy may have a specific defect in the circadian control of sleep and wakefulness. Considerable basic research supports this hypothesis. Narcolepsy with cataplexy is caused by a loss of the orexin/hypocretin-producing neurons.8–10 Since the orexin neurons receive both direct and indirect signals from the SCN and send projections to many state-regulatory brain regions, they are anatomically well positioned to mediate the circadian timing of sleep and wakefulness.11–17 Extracellular levels of orexin vary in a circadian pattern, with high levels during the waking period, and lesions of the SCN abolish this rhythm.18–20 Furthermore, nonspecific lesions of the orexin field or of the pathways between the SCN and the orexin neurons disrupt the timing of sleep/wake behavior.12,13,21 We therefore hypothesized that the orexin neurons are an essential relay for the circadian signals that time and consolidate sleep and wake. To determine whether the orexin neurons are necessary for the circadian control of sleep and wakefulness, we examined free-running circadian rhythms in 2 different strains of orexin deficient mice: orexin/ataxin-3 (Atx) mice with an acquired, selective loss of the orexin/hypocretin neurons and orexin peptide knockout (KO) mice.22,23

Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin.