Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study.

BACKGROUND: Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS. METHODS: In this small cohort observation study, we examined the efficacy of bilateral sequential theta-burst stimulation (bsTBS) in 8 treatment resistant depression (TRD) military veterans with PTSD comorbidity stemming from military service experience. RESULTS: bsTBS was generally well tolerated and resulted in 25% and 38% remission and response rates on Depression scores respectively; 25% remission and response rate on PTSD scores. DISCUSSION: This study demonstrates preliminary feasibility and safety of bsTBS in TRD with comorbid military service related PTSD. We concluded that this paradigm might hold promise as a therapeutic tool to help patients with TRD co-morbid with military service related PTSD. Further adequately powered studies to compare rTMS treatment paradigms in this patient group are warranted.

Disentangling Reversal-learning Impairments in Frontotemporal Dementia and Alzheimer Disease.

BACKGROUND: Individuals with frontotemporal dementia (FTD) often present with poor decision-making, which can affect both their financial and social situations. Delineation of the specific cognitive impairments giving rise to impaired decision-making in individuals with FTD may inform treatment strategies, as different neurotransmitter systems have been associated with distinct patterns of altered decision-making. OBJECTIVE: To use a reversal-learning paradigm to identify the specific cognitive components of reversal learning that are most impaired in individuals with FTD and those with Alzheimer disease (AD) in order to inform future approaches to treatment for symptoms related to poor decision-making and behavioral inflexibility. METHOD: We gave 30 individuals with either the behavioral variant of FTD or AD and 18 healthy controls a stimulus-discrimination reversal-learning task to complete. We then compared performance in each phase between the groups. RESULTS: The FTD group demonstrated impairments in initial stimulus-association learning, though to a lesser degree than the AD group. The FTD group also performed poorly in classic reversal learning, with the greatest impairments being observed in individuals with frontal-predominant atrophy during trials requiring inhibition of a previously advantageous response. CONCLUSION: Taken together, these results and the reversal-learning paradigm used in this study may inform the development and screening of behavioral, neurostimulatory, or pharmacologic interventions aiming to address behavioral symptoms related to stimulus-reinforcement learning and response inhibition impairments in individuals with FTD.

Depressive Symptoms Are Associated With More Negative Functional Outcomes Than Anxiety Symptoms in Persons With Multiple Sclerosis.

Depression and anxiety are common among persons with multiple sclerosis (MS), and both negatively affect functional status. However, studies rarely account for overlap in depressive and anxiety symptoms on functional outcomes among people with MS. The authors aimed to examine the differential impact of depression and anxiety, measured by the Anxiety and Depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), on functional outcomes among people with MS. Using a retrospective chart review of 128 people with MS, the authors used exploratory structural equation modeling to examine the relation of HADS-A and HADS-D to functional outcomes, namely employment status, fatigue (with the Fatigue Severity Scale), disability (with the Expanded Disability Status Scale [EDSS]), and cognition (with the Symbol Digit Modalities Test [SDMT]). After the authors controlled for the effects of covariates, HADS-A was negatively associated with EDSS (ß=-0.22, p<0.05) and positively associated with vocation (ß=0.23, p<0.05). In contrast, HADS-D was positively correlated with fatigue (ß=0.37, p<0.05) and EDSS (ß=0.26, p<0.05) and negatively correlated with vocation (ß=-0.32, p<0.05) and SDMT (ß=-0.28, p<0.05). HADS-A and HADS-D explained 5% of the variability in employment, 14.5% in fatigue, 1.6% in EDSS, and 4.3% in SDMT, beyond the effects of the covariates. Depressive symptoms have a significant negative impact on functional outcomes among people with MS, relative to anxiety symptoms. These findings support the importance of identifying and treating depressive symptoms among people with MS.

Depressive Symptoms Negatively Impact Montreal Cognitive Assessment Performance: A Memory Clinic Experience.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a general cognitive screening tool that has shown sensitivity in detecting mild levels of cognitive impairment in various clinical populations. Although mood dysfunction is common in referrals to memory clinics, the influence of mood on the MoCA has to date been largely unexplored. METHOD: In this study, we examined the impact of mood dysfunction on the MoCA using a memory clinic sample of individuals with depressive symptoms who did not meet criteria for a neurodegenerative disease. RESULTS: Half of the group with depressive symptoms scored below the MoCA-suggested cutoff for cognitive impairment. As a group, they scored below healthy controls, but above individuals with Alzheimer's disease and frontotemporal dementia. A MoCA subtask analysis revealed a pattern of executive/attentional dysfunction in those with depressive symptoms. CONCLUSIONS: This observed negative impact of depressive symptomatology on the MoCA has interpretative implications for its utility as a cognitive screening tool in a memory clinic setting.

The influence of personality in persons with MS.

BACKGROUND: Comprehending the influence of personality traits on functional outcomes in persons with Multiple Sclerosis (pwMS) can aid in tailoring interventions and support strategies. We explored how demographic variables and personality traits predicted current vocation, information processing speed, anxiety and depression symptoms, and disability level in pwMS. METHODS: We used a retrospective chart review on pwMS treated at the London (ON) MS Clinic, that assessed demographic data and personality traits. Participants were 384 (68.8 % females, mean age of 37.8, SD = 10.4) individuals with relapsing and primary progressive MS. We performed hierarchical linear regressions to predict outcomes while considering demographic variables and personality traits. RESULTS: Younger age, higher education, and conscientiousness were significant predictors for better information processing speed, current vocation, depression symptoms, and disability level. Neuroticism was positively associated with anxiety and depression symptoms, while extraversion was negatively associated with depression symptoms. Women showed higher anxiety symptoms, while men showed higher depression symptoms. CONCLUSION: Personality traits, such as neuroticism and conscientiousness, influence psychological outcomes in pwMS. Younger age and higher education are associated with better functional outcomes. Thus, when considering personality traits, future interventions should focus on those with higher neuroticism and lower scores on both extraversion and conscientiousness. Consideration of social support, coping strategies, and disease severity in future research may further enrich our understanding of MS outcomes.

Self-reported cognitive function mediates the relationship between employment status and cognitive functioning in persons with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is common in people with MS (PwMS). Evidence is lacking for the self-reported CI's mediation effect on employment status and objective cognitive performance. Self-reported CI was found to be unreliable and seemed to be more associated with depression rather than formal cognitive performance. We hypothesized that the link between subjective and objective assessments of cognitive functions, mood, and employment status may be more complex in PwMS than previously reported. OBJECTIVE: The aims of this study are the following: (Romero-Pinel et al., 2022) to determine whether employment status could affect performance in cognitive function testing and (Rao et al., 1991) whether their relationship may be mediated by self-reported CI; and (Deluca et al., 2013) to determine whether self-reported depression interacts with self-reported CI in influencing performance in various cognitive domains in PwMS. METHODOLOGY: A retrospective study was performed involving PwMS who completed the self-report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale-depression scale (HADS-D), Minimal Assessment of Cognitive Function in MS (MACFIMS) and had data regarding employment status. Included PwMS were classified as employed or unemployed. A structural equation modeling (SEM) approach was taken due to the advantage of examining multiple cognitive outcomes simultaneously while accounting for shared associations. First, a latent factor of memory and executive functioning modeled the error-free associations between both factors and a processing speed task (SDMT). Next, the model tested for the indirect effect of self-reported cognition (MSNQ) on employment status differences in each outcome (memory, speed, and executive functioning). Finally, we tested interactions between MSNQ and HADS-D on each of the outcomes. RESULTS: We included 590 PwMS: 72.5% female, mean age 44.2 years (SD = 10.5), mean disease duration 8.6 years (SD 9.0). The majority (n = 455, 77.1%) had relapsing MS; 357 (60.5%) were employed. About half (n = 301, 51%) did not report CI on the MSNQ; of those, 213 (70.8%) were employed. The mean MSNQ for employed PwMS was 24.5 (SD = 10.7) and 29.8 (SD = 11.2) for unemployed PwMS. Employed PwMS had significantly better memory (ß = .16, p < .05), executive functioning (ß = .25, p < .05), and processing speed (ß = .22, p < .05). MSNQ partially indirectly mediated the effect of employment status on memory (Δß = .03, p < .05) and executive functioning (Δß = .03, p < .05) and processing speed (Δß = .04, p < .05), indicating that self-report CI partially explains the influence of employment status on these cognitive domains. The association between MSNQ with both memory and executive functioning was moderated by depression, meaning that in PwMS with high HADS-D scores, MSNQ was more strongly related to worse memory and executive functioning. The final model was an acceptable fit to the data (χ2(87) = 465.07, p < .05; CFI = .90, RMSEA = .08, 90% CI [.06, .09], SRMR = .05) explaining 41.20%, 38.50% and 33.40% of the variability in memory, executive functioning, and processing speed, respectively. CONCLUSION: Self-reported CI partially explains the associations between employment status and objective cognitive assessment in PwMS. Depression may moderate the relationship between self-reported cognitive assessment and objective cognitive performance. Thus, employment status and mood may guide the interpretation of self-reported CI.

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review.

Background: We aimed to determine the effects and tolerability of repetitive transcranial magnetic stimulation (rTMS) on apathy in patients with neurodegenerative conditions, mild cognitive impairment (MCI), stroke, and traumatic brain injury (TBI) via systematic review. Methods: We conducted a systematic search in major electronic health databases, including PubMed, Scopus, and PsycINFO, covering the period from inception to June 2023. Comparative clinical trials and cohort studies, and studies with before-after designs were considered for inclusion. We used the Cochrane Risk of Bias and the National Institutes of Health (NIH) tools to assess methodological quality. Results: Out of 258 records identified, 14 studies met our eligibility criteria (11 randomized controlled trials (RCT) and 3 studies utilized before-and-after designs) with a total of 418 patients (overall female-to-male ratio 1:1.17) included in the review. The overall methodological quality of the included studies was assessed to be fair to good. The stimulation parameters used varied considerably across the studies. The summary findings of our review indicate the following observations on the effects of rTMS on apathy: (1) the results of all included studies in Alzheimer's disease investigating the effects of rTMS on apathy have consistently shown a positive impact on apathy; (2) the majority of studies conducted in Parkinson's disease have not found statistically significant results; (3) a single study (RCT) on patients with primary progressive aphasia demonstrated significant beneficial effects of rTMS on apathy; (4) the trials conducted on individuals with MCI yielded varying conclusions; (5) one study (RCT) in chronic stroke suggested that rTMS might have the potential to improve apathy; (6) one study conducted on individuals with mild TBI did not find a significant favorable association on apathy; and (7) the use of different rTMS protocols on the populations described is generally safe. Conclusion: The feasibility of utilizing rTMS as a treatment for apathy has been suggested in this review. Overall, limited evidence suggests that rTMS intervention may have the potential to modify apathy among patients with AD, PPA, MCI and chronic stroke, but less so in PD and mild TBI. These findings require confirmation by larger, well-designed clinical trials.

Does cognitive training improve attention/working memory in persons with MS? A pilot study using the Cogmed Working Memory Training program.

BACKGROUND: Cognitive deficits, especially in attention, are common in persons with MS (PwMS) and are associated with clinically meaningful outcomes, such as work disability and lower quality of life (QOL). In this study, we aimed to determine whether Cogmed Working Memory Training (CWMT) improves attention/working memory in PwMS displaying impairment in these domains. METHODS: This single blind, randomized controlled, pilot study compared the effects of CWMT, a five-week evidenced-based computer-assisted training program that is supported by weekly meetings with a coach, to standard medical care (treatment as usual). We recruited PwMS from one MS center (London (ON) Canada), aged 18-64, with an Expanded Disability Status Scale (EDSS) score of ≤ 7.0, and a visual acuity (corrected) of at least 20/70. Potential subjects had to demonstrate impaired attention on at least two of three measures (Paced Auditory Serial Addition Test [PASAT], Symbol Digit Modalities Test [SDMT], and/or DKEFS Color-Word Interference Test); these measures also served as the primary study outcomes. Subjects were randomized to either the CWMT or treatment as usual. Secondary cognitive outcomes included other measures of attention, memory, as well as a self-reported cognitive function measure. Self-reported measures of mood (depression and anxiety), pain, and QOL were also included as other secondary outcomes. Subjects received assessments at baseline, post-treatment, and 6-month follow-up, or an equivalent time period for the treatment as usual group. The two groups were compared at baseline on background measures using independent samples t-tests, Chi-Square tests, and Mann-Whitney U tests. To analyze primary and secondary outcomes, a non-parametric approach was used due the small sample size and that many of our outcomes did not meet assumptions for parametric analyses. Friedman's test was conducted followed by post hoc pairwise comparisons within each group using Wilcoxon Signed-Rank tests with Bonferroni corrected post hoc contrasts, which allowed us to examine for differences between time points. RESULTS: Of 30 subjects, 15 were assigned to CWMT. Significant training effects were noted in 1 of 3 primary attentional outcomes (DKEFS Color-Word Interference Test), 2 of 3 secondary attentional outcomes (Letter-Number Sequencing, Digit Span), and 1 mood scale (Hospital Anxiety and Depression scale (HADS) - Depression Subscale), ps < .025. No significant changes were observed in the treatment as usual group. CONCLUSION: This pilot study demonstrates that cognitive training with CWMT has the potential to improve attention/working memory in PwMS, as well as a potential positive effect on mood, in PwMS. Further exploration of this intervention in PwMS with attention/working memory impairment is warranted.

Predictors of vocational status among persons with multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a common cause of neurological disability in young to middle-aged adults, resulting in physical, psychosocial, and cognitive impairments. Manifestation of these symptoms during crucial work-life years can greatly influence the ability of persons with (PwMS) to retain employment. It is unknown what factors are most important in leading to work disability, and if/how these different factors interact with each other and result in work disability. OBJECTIVE: To determine significant predictors of vocational status among PwMS using a structural equation modeling approach. METHODS: A retrospective chart review identified PwMS at an academic tertiary care hospital. The following data was collected: demographics and disease characteristics, vocational status, physical disability status (Expanded Disability Status Scale, EDSS), fine motor function (Nine Hole Peg Test, NHPT), generalized fatigue (Fatigue Severity Scale, FSS), mood and anxiety symptoms (Hospital Anxiety and Depression Scale, HADS) and cognitive function (Symbol Digit Modalities Test, SDMT). An exploratory structural equation model (SEM) was developed to examine the predictive utility of clinical and psychosocial variables on vocational status after controlling for demographic and disease characteristics. The fit of the model to the data was examined using the comparative fit index (CFI), normal fit index (NFI), root-mean-squared error of approximation (RMSEA), and standardized root mean residual (SRMR). RESULTS: There were 158 PwMS included in the analysis. The final model demonstrated that SDMT (ß = 0.16), EDSS (ß = -0.33), and HADS-D (ß = -0.23) significantly predicted vocational status (ps < 0.05). It explained 37% of the variance and provided a good fit to the data (χ2(11) = 13.01, p > 0.05, SRMR = 0.055, RMSEA = 0.034, NFI = 0.94, CFI = 0.99. CONCLUSIONS: Physical disability, depressive symptoms, and reduced information processing affect work-related disability and vocational status among PwMS. Interventions targeting these factors should be prioritized by clinicians.

Financial capacity in frontotemporal dementia and related presentations.

BACKGROUND: Changes in financial judgement and skills can herald a neurodegenerative dementia and are a common reason for referral for cognitive neurologic assessment. However, patients with neurodegenerative diseases affecting the frontal or temporal lobes may perform well on standard cognitive tests, complicating clinical determinations about their diagnosis and financial capacity. METHODS: Forty-five patients with possible or probable FTD or Alzheimer's disease and 22 healthy controls completed two financial assessment batteries, the FACT and the FCAI. Patients' performance was compared to study partner estimates of patients' financial abilities. RESULTS: All three patient groups performed worse than controls on both the FACT and the FCAI. Study partners over-estimated the performance of patients with Alzheimer's disease. CONCLUSIONS: These initial findings suggest that accurate clinical assessment of financial skills and judgement in patients with possible neurodegenerative dementias requires performance-based assessment.

Diagnosis and treatment of dementia: 2. Diagnosis.

BACKGROUND: Dementia can now be accurately diagnosed through clinical evaluation, cognitive screening, basic laboratory evaluation and structural imaging. A large number of ancillary techniques are also available to aid in diagnosis, but their role in the armamentarium of family physicians remains controversial. In this article, we provide physicians with practical guidance on the diagnosis of dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that pertained to key diagnostic issues in dementia. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: Of the 1591 articles we identified on all aspects of dementia diagnosis, 1095 met our inclusion criteria; 620 were deemed to be of good or fair quality. From a synthesis of the evidence in these studies, we made 32 recommendations related to the diagnosis of dementia. There are clinical criteria for diagnosing most forms of dementia. A standard diagnostic evaluation can be performed by family physicians over multiple visits. It involves a clinical history (from patient and caregiver), a physical examination and brief cognitive testing. A list of core laboratory tests is recommended. Structural imaging with computed tomography or magnetic resonance imaging is recommended in selected cases to rule out treatable causes of dementia or to rule in cerebrovascular disease. There is insufficient evidence to recommend routine functional imaging, measurement of biomarkers or neuropsychologic testing. INTERPRETATION: The diagnosis of dementia remains clinically integrative based on history, physical examination and brief cognitive testing. A number of core laboratory tests are also recommended. Structural neuroimaging is advised in selected cases. Other diagnostic approaches, including functional neuroimaging, neuropsychological testing and measurement of biomarkers, have shown promise but are not yet recommended for routine use by family physicians.

Short Report: Prevalence of Cognitive Impairment in Newly Diagnosed Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) and can manifest early in the disease process, sometimes as early as the first demyelinating event. However, the frequency of cognitive impairment in a newly diagnosed MS population has not been evaluated comprehensively in a clinical population. We sought to examine the prevalence of cognitive impairment in relapsing-remitting MS (RRMS) within a year of diagnosis in a clinic where cognitive testing at diagnosis is part of routine practice. METHODS: A retrospective medical record review of persons with RRMS assessed in a cognitive MS clinic identified 107 patients assessed by the Minimal Assessment of Cognitive Function in Multiple Sclerosis battery within 1 year of a confirmed RRMS diagnosis. RESULTS: The cohort was predominantly female (n = 82 [76.6%]) and white (n = 93 [86.9%]). Only 36 patients (33.6%) were diagnosed as having RRMS based on a second clinical event. Processing speed was the most frequently impaired domain (n = 38 [35.5%]). Only 37 patients (34.6%) were within normal limits on all cognitive domains. Regarding mood symptoms, 25 patients (23.4%) were positive for depressive symptoms; 59 (55.1%), for anxiety. Severe fatigue was correlated with a lower score on the Symbol Digit Modalities Test (SDMT) (r = -0.380, P < .001), and higher depressive scores were correlated with lower performance on the SDMT (r = -0.397, P < .001) and the Paced Auditory Serial Addition Test (r = -0.254, P = .009). CONCLUSIONS: Cognitive impairment, specifically processing speed, and mood symptoms are frequently present in persons with newly diagnosed RRMS.

Neuropsychological testing and assessment for dementia.

This evidence-based review examines the utility of brief cognitive tests and neuropsychological testing (NPT) in the detection and diagnosis of mild cognitive impairment (MCI) and dementia. All patients presenting with cognitive complaints are recommended to have a brief screening test administered to document the presence and severity of memory/cognitive deficits. There is fair evidence to support the use of a range of new screening tests that can detect MCI and mild dementia with higher sensitivity (>or=80%) than the Mini-Mental State Exam (MMSE). NPT should be part of a clinically integrative approach to the diagnosis and differential diagnosis of dementia. It should be applied selectively to address specific clinical and diagnostic issues including: 1) The distinction between normal cognitive functioning in the aged, MCI and early dementia: there is fair evidence that NPT can document the presence of specific diagnostic criteria and provide additional useful information on the pattern of memory/cognitive impairment. 2) The evaluation of risk for Alzheimer disease (AD) or other types of dementia in persons with MCI: there is fair evidence that NPT measures or profiles can predict progression to dementia (predictive accuracy ranges from approximately 80 to 100%, sensitivities from 53 to 80%, and specificities from 67 to 99%). 3) DIFFERENTIAL DIAGNOSIS: There is fair evidence that NPT can complement clinical history and neuroimaging in determining the dementia etiology. Different dementia types have distinguishable NPT profiles though these may be stage-dependent, and increased sensitivity may be at the expense of specificity. 4) When NPT is part of a comprehensive assessment, which also entails clinical interviews and consideration of other clinical data, there is good evidence that it can contribute to management decisions in MCI and dementia, including the determination of retained and impaired cognitive abilities, their functional and vocational impact, and opportunities for cognitive rehabilitation.

Comparing depression screening tools in persons with multiple sclerosis (MS).

OBJECTIVE: Depression is more common among persons with multiple sclerosis (MS) than the general population. Depression in MS is associated with reduced quality of life, transition to unemployment, and cognitive impairment. Two proposed screening measures for depression in MS populations are the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory-Fast Screen (BDI-FS). Our objective was to compared the associations of the BDI-FS and the HADS-D scores with history of depressive symptoms, fatigue, and functional outcomes to determine the differential clinical utility of these screening measures among persons with MS. METHOD: We reviewed charts of 133 persons with MS for demographic information; scores on the HADS, BDI-FS, a fatigue measure, and a processing speed measure; and employment status. RESULTS: Structural equation modeling results indicated the HADS-D predicted employment status, disability status, and processing speed more effectively than did the BDI-FS, whereas both measures predicted fatigue. CONCLUSIONS: This study suggests the HADS-D is more effective than the BDI-FS in predicting functional outcomes known to be associated with depression among persons with MS. (PsycINFO Database Record

Dialectical Behavior Group Therapy is Feasible and Reduces Emotional Dysfunction in Multiple Sclerosis.

We examined whether dialectical behavior therapy (DBT) was feasible and effective in multiple sclerosis (MS). A convenience sample of 20 patients with anxiety or depression symptoms received either DBT (n = 10) or standard medical care (n = 10). The DBT protocol was found to be feasible in the MS population studied (e.g., good retention and acceptability). For the DBT group, significant improvements were demonstrated in self-rated and clinician-rated depressive symptoms, clinician-rated anxiety symptoms, self-rated general psychopathology symptoms, and quality of life. In contrast, the standard medical care group retained for exploratory purposes showed no significant improvements. This pilot work provides preliminary support for the utility of DBT in MS, but further work is needed to clarify this benefit using a large, randomized controlled approach.

The evolution and pathology of frontotemporal dementia.

This is a clinicopathologic study of a prospective, clinic-based cohort of patients with frontotemporal dementia (FTD)/Pick complex, who were followed to autopsy. A total of 60 patients with the clinical syndromes of the behavioural variant of FTD (FTD-bv) (n = 32), primary progressive aphasia (PPA) (n = 22), corticobasal degeneration syndrome (CBDS) (n = 4) and progressive supranuclear palsy (PSP) (n = 2) at onset, referred to a cognitive neurology clinic who had subsequent post-mortem examination were included. The most common histological variety was motor neurone disease type inclusion (MNDI) (n = 18), followed by corticobasal degeneration (CBD) (n = 12), then Pick's disease (n = 6), dementia lacking distinctive histology (DLDH) (n = 6) and PSP (n = 3). Others fulfilled the histological criteria for Alzheimer's disease combined with glial pathology (n = 6), Alzheimer's disease only (n = 4), Lewy body variant (n = 2), prion disease (n = 1), vascular dementia (n = 1) and undetermined (n = 1). The most common first syndrome among the MNDI and DLDH (tau negative) pathologies was FTD-bv, but subsequently progressive aphasia (PA), occasionally CBDS and semantic dementia also developed. Tau positive histologies of CBD, PSP and Pick bodies were most frequently associated with PPA onset or CBDS/PSP, but behavioural symptoms were also common. Age of onset was earlier in tau negative cases, but the duration of illness and gender distribution were about the same in all histological variants. Although the tau negative and positive histologies are predicted to some extent by the clinical onset, the extent of the overlap and the convergence of the syndromes in the course of the disease argue in favour of maintaining the clinical and pathological varieties under a single umbrella.

Are Age-Related Differences Uniform Across Different Inhibitory Functions?

OBJECTIVES: In the current experiment, we examined the relative age-sensitivity of 3 inhibitory functions: access, deletion, and restraint by taking into consideration their underlying control processes: proactive and reactive control. METHODS: The 3 inhibitory functions were measured using a sequential flanker task. Young (age: 18-35, n = 24) and older adults (age: 60-75, n = 25) first memorized a series of 8 animal words in a fixed order. In the test phase, these stimuli were presented randomly either singly or with flankers and participants responded "yes" or "no" based on the prelearned sequence. In the access trials, flankers were either ahead of the current target or unrelated. In the deletion trials, flankers were previous target items. In the restraint trials, the flanker cues (XXXX) prompted the participants to withhold responses occasionally. Unflanked trials served as the baseline condition. RESULTS: Age-related differences in the magnitude of inhibition effects were largest in restraint, followed by deletion. No age-related differences were observed in access. DISCUSSION: Our findings suggest that the magnitude of age-related differences in inhibitory functions is contingent on the degree of proactive control recruited by a given inhibitory function.

The mediating role of processing speed in the relationship between depressive symptoms and cognitive function in multiple sclerosis.

INTRODUCTION: Although disorders of mood and cognition are frequently observed in multiple sclerosis, their relationship remains unclear. We aimed to investigate whether this mood-cognition relationship is mediated by inefficient processing speed, a deficit typically associated with mood symptomatology in the psychiatric literature and a common deficit observed in multiple sclerosis patients. METHOD: In this study, comprehensive cognitive data and self-reported mood data were retrospectively analyzed from 349 patients with relapsing remitting multiple sclerosis. We performed a bootstrapping analysis to examine whether processing speed provided an indirect means by which depressive symptoms influenced cognitive functioning, specifically memory and executive function. RESULTS: We observed that processing speed mediated the relationship between depressive symptoms and measures of memory and executive function. Interestingly, exploratory analyses revealed that this mediational role of processing speed was specific to MS patients who were younger, had a lower disability level, and had fewer years since MS diagnosis. CONCLUSIONS: Together, these findings have implications for mood and cognitive intervention with multiple sclerosis patients.

Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability.

OBJECTIVE: To determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD). METHODS: We conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects. RESULTS: All 3 doses of intranasal oxytocin were safe and well tolerated. CONCLUSIONS: A multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.