Computerized Games versus Crosswords Training in Mild Cognitive Impairment.

BACKGROUND: Mild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear. METHODS: In a two-site, single-blinded, 78-week trial, participants with MCI - stratified by age, severity (early/late MCI), and site - were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed. RESULTS: Among 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, -1.44; 95% confidence interval [CI], -2.83 to -0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, -2.45; SE, 0.89; 95% CI, -4.21 to -0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, -1.08; 95% CI, -1.97 to -0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]). CONCLUSIONS: Home-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.).

Testing the Mechanism of Action of Computerized Cognitive Training in Young Adults with Depression: Protocol for a Blinded, Randomized, Controlled Treatment Trial.

BACKGROUND: Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). Cognitive symptoms commonly persist with the resolution of affective symptoms and increase risk of relapse and recurrence. The cognitive control network is comprised of brain areas implicated in EF and mood regulatory functions. Prior research has demonstrated the effectiveness of computerized cognitive training (CCT) focused on PS and EF in mitigating both cognitive and affective symptoms of depression. METHODS: Ninety participants aged 18-29 with a current diagnosis of major depressive disorder or persistent depressive disorder, or a Hamilton Depression Rating Scale score ≥12, will be randomized to either PS/EF CCT, verbal CCT, or waitlist control. Participants in the active groups will complete 15 min of training 5 days/week for 8 weeks. Clinical and neuropsychological assessments will be completed at baseline, week 4, week 8, and 3-month follow-up. Structural and functional magnetic resonance imaging (fMRI) will be completed at baseline and week 8. We will compare changes in mood, cognition, daily functioning, and fMRI data. We will explore cognitive control network functioning using resting-state and task-based fMRI. RESULTS: Recruitment began in October 2019; we expect to finish recruitment by April 2022 and subsequently begin data analysis. CONCLUSIONS: This study is innovative in that it will include both active and waitlist control conditions and will explore changes in neural activation. Identifying the neural networks associated with improvements following CCT will allow for the development of more precise and effective interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03869463; https://clinicaltrials.gov/ct2/show/NCT03869463.

Vascular depression for radiology: A review of the construct, methodology, and diagnosis.

Vascular depression (VD) as defined by magnetic resonance imaging (MRI) has been proposed as a unique subtype of late-life depression. The VD hypothesis posits that cerebrovascular disease, as characterized by the presence of MRI-defined white matter hyperintensities, contributes to and increases the risk for depression in older adults. VD is also accompanied by cognitive impairment and poor antidepressant treatment response. The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely, if ever, discussed in radiology journals. The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community. Case reports are highlighted in order to illustrate the profile of VD in terms of radiological, clinical, and neuropsychological findings. A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi- and fully-automated volumetric methods. These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD. Additionally, these rating methods have implications for the growing field of computer assisted diagnosis. Since VD has been found to have a profile that is distinct from other types of late-life depression, neuroradiologists, in conjunction with psychiatrists and psychologists, should consider VD in diagnosis and treatment planning.

Clinical and radiological characteristics of early versus late mild cognitive impairment in patients with comorbid depressive disorder.

OBJECTIVE: The classification of mild cognitive impairment (MCI) continues to be debated though it has recently been subtyped into late (LMCI) versus early (EMCI) stages. Older adults presenting with both a depressive disorder (DEP) and cognitive impairment (CI) represent a unique, understudied population. Our aim was to examine baseline characteristics of DEP-CI patients in the DOTCODE trial, a randomized controlled trial of open antidepressant treatment for 16 weeks followed by add-on donepezil or placebo for 62 weeks. METHODS/DESIGN: Key inclusion criteria were diagnosis of major depression or dysthymic disorder with Hamilton Depression Rating Scale (HAM-D) score >14, and cognitive impairment defined by MMSE score ≥21 and impaired performance on the WMS-R Logical Memory II test. Patients were classified as EMCI or LMCI based on the 1.5 SD cutoff on tests of verbal memory, and compared on baseline clinical, neuropsychological, and anatomical characteristics. RESULTS: Seventy-nine DEP-CI patients were recruited of whom 39 met criteria for EMCI and 40 for LMCI. The mean age was 68.9, and mean HAM-D was 23.0. Late mild cognitive impairment patients had significantly worse ADAS-Cog (P < .001), MMSE (P = .004), Block Design (P = .024), Visual Rep II (P = .006), CFL Animal (P = .006), UPSIT (P = .051), as well as smaller right hippocampal volume (P = .037) compared to EMCI patients. MRI indices of cerebrovascular disease did not differ between EMCI and LMCI patients. CONCLUSIONS: Cognitive and neuronal loss markers differed between EMCI and LMCI among patients with DEP-CI, with LMCI being more likely to have the clinical and neuronal loss markers known to be associated with Alzheimer's disease.

Growing older with drug-resistant epilepsy: cognitive and psychosocial outcomes.

We aimed to investigate the cognitive and psychosocial outcomes of patients older than 50 with drug-resistant temporal lobe epilepsy as compared to a younger cohort. One hundred and thirty-one patients with temporal lobe epilepsy (47% age ≥ 50) who underwent comprehensive neuropsychological testing were retrospectively identified. A comparison of percentage of Z scores < - 1.5 between the older and younger cohort on Trail Making Tests A and B, Boston Naming Test, Rey Auditory Verbal Learning Test (RAVLT) delayed recall, and Rey-Osterrieth complex figure test delayed recall was performed as well as the presence of disability due to epilepsy and depression scores. Grading of white matter hyperintensities on MRI was also performed. Older patients with epilepsy were more likely to score Z < - 1.5 on the RAVLT (54.1 vs 32.8%) and were more likely to be on disability due to their seizures (23.0 vs 5.7%). A higher grade of white matter hyperintensities correlated with worse performance on Trail Making Test A, while a higher number of anti-epileptic drugs (AEDs) correlated with worse performance on Trail Making Test B regardless of age. The results of this study reveal that older patients with drug-resistant epilepsy are a vulnerable population with an impaired cognitive profile. In addition, limiting the number of AEDs and addressing markers of small vessel disease should also be prioritized by clinicians.

Clark's nutcrackers (Nucifraga columbiana) are sensitive to distance, but not lighting when caching in the presence of a conspecific.

We examined the caching behavior of the Clark's nutcracker (Nucifraga columbiana), a relatively asocial corvid bird, during social and non-social conditions with conspecifics. Past work by Dally et al., (2004, 2005a) has found that the related but more social scrub jay (Aphelocoma californica) caches food in locations that are far away or that are more dimly illuminated when in the presence of an observer. Here, we used procedures comparable to those of Dally's group to examine if the less social nutcracker is also sensitive to these same factors when caching in the presence of a conspecific. We found that nutcrackers cached nuts farther away, but showed no preference for caching in a dimly compared to a brightly illuminated area when in the presence of a conspecific observer. When comparing the measures of cache protection used in the past work with scrub jays the results are consistent with the social organization of these birds; that is, the less social nutcracker engaged in fewer cache protection behaviors than the more social scrub jays, However, we explore other possible explanations for our findings given the wider body of literature on corvid cache protection suggesting that nutcrackers and scrub jays may be more comparable.

Two systems drive attention to rewards.

How options are framed can dramatically influence choice preference. While salience of information plays a central role in this effect, precisely how it is mediated by attentional processes remains unknown. Current models assume a simple relationship between attention and choice, according to which preference should be uniformly biased towards the attended item over the whole time-course of a decision between similarly valued items. To test this prediction we considered how framing alters the orienting of gaze during a simple choice between two options, using eye movements as a sensitive online measure of attention. In one condition participants selected the less preferred item to discard and in the other, the more preferred item to keep. We found that gaze gravitates towards the item ultimately selected, but did not observe the effect to be uniform over time. Instead, we found evidence for distinct early and late processes that guide attention according to preference in the first case and task demands in the second. We conclude that multiple time-dependent processes govern attention during choice, and that these may contribute to framing effects in different ways.