Widespread Cognitive Deficits Research Articles

Association of plasma biomarkers with cognitive domains across three neurodegenerative diseases and cerebrovascular disease

AbstractBackgroundIt is critical to better understand the value of plasma biomarkers in predicting cognitive deficits before widespread use as diagnostic and prognostic tools in specialized clinics and as markers of neurodegenerative disease progression in trials. Herein, we investigate their association with five cognitive domains across three common neurodegenerative diseases and cerebrovascular disease.MethodPatients from the curated multi‐site Ontario Neurodegenerative Disease Research Initiative (ONDRI) were included in this study, classified by diagnostic group: Alzheimer’s disease/Mild cognitive impairment (AD/MCI, n = 126, age = 71.0±8.2, 55%M), frontotemporal dementia spectrum disorders (FTD, n = 53, age = 67.8±7.1, 64%M), Parkinson’s disease (PD, n = 140, age = 67.9±6.3, 78%M) and cerebrovascular disease (CVD, n = 161, age = 69.2±7.4, 68%M). Plasma concentrations of Aβ40 and Aβ42 (Aβ42/40 ratio), glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and phosphorylated‐tau181 (p‐tau181) were measured using high‐sensitivity Simoa assays. Scores from a 26‐test comprehensive neuropsychological assessment were used to compute composite z‐scores for five cognitive domains: attention & working memory, executive function, language, memory, and visuospatial function. Linear regression models controlling for age, sex, education and APOE E4 allele were used to test the association between plasma biomarkers and cognitive domains in each group separately.ResultIn AD/MCI, higher levels of GFAP, NfL and p‐tau181 were all associated with worse attention & working memory, executive function, and memory. In PD, higher levels of NfL were associated with worse attention & working memory, executive function, and visuospatial function; higher levels of GFAP were also associated with worse executive function. In CVD, higher levels of GFAP were associated with worse executive function, memory and visuospatial function; higher levels of p‐tau181 were also associated with worse memory. In FTD, no associations were found.ConclusionPlasma biomarkers indicative of neuronal and glial pathology are useful to predict the severity of widespread cognitive deficits in AD/MCI, PD, and CVD. Interestingly, p‐tau181 predicted memory deficits in both AD/MCI and CVD, suggesting potential mixed disease or pathological overlap. Plasma Aβ42/40 does not appear to predict any cognitive deficits in any of the neurodegenerative diseases studied. As FTD is highly heterogeneous and had the least number of patients, we are possibly lacking power to detect effects in this group.

10 Comprehensive Neuropsychological Findings in Erdheim-Chester Disease: Case Report

Objective:Erdheim-Chester disease (ECD) is a rare disorder characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD primarily affects adults, and symptoms vary depending upon the specific location and severity. Etiology is not always known, but some patients with ECD may have a non-inherited genetic change that allows histiocytes to reproduce uncontrollably. Currently, the cognitive outcomes of ECD are not well understood, and there are no previous neuropsychological findings in the literature. Thus, the objective of this case study was to describe the neuropsychological presentation and findings of an ECD case to inform diagnosis and treatment better.Participants and Methods:The patient was a 64-year-old white, non-Hispanic, right-handed man diagnosed with ECD in 2017. ECD accounted for a constellation of medical problems, including diabetes insipidus, hypogonadism, and interstitial lung disease. A brain MRI in 2018 revealed orbital nodularities and pituitary infiltration thought to be consistent with ECD. The patient first noticed cognitive functioning difficulties in 2020 primarily related to short-term memory. Approximately two years later, he noted significant cognitive changes, including difficulties recalling recent events, dates, and conversations, problem-solving, and planning. He had difficulty driving and had two recent car accidents when leaving his driveway. Physically, he reported increased fatigue, unsteadiness, and occasional falls. In 2022, he had a brain MRI that demonstrated a progression of multiple diffuse cerebral, cerebellum, and brainstem lesions and cerebral volume loss compared to prior imaging. He was referred for a neuropsychological assessment to rule out a neurodegenerative disorder.Results:Neuropsychological data demonstrated moderate-to-severe deficits on tests of basic spatial working memory, visually based processing speed, visual memory, letter verbal fluency, and semantic verbal fluency. He demonstrated mild-to-moderate deficits on tests of basic auditory attention, verbal memory, higher-level visuospatial processing, abstract nonverbal reasoning, multistep, organization and planning, self-monitoring of performance quality, and fine hand and motor dexterity. He demonstrated variable initial learning of new information across modalities, although he did benefit from structured verbal material. Recognition was variable, with difficulty demonstrated in discriminating visual information presented, from similar competing information, along with availability recalling visual information. He showed average auditory-based divided attention, confrontational object naming, and abstract verbal reasoning. Regarding his emotional functioning, he reported mild depressive and anxiety symptoms.Conclusions:To the best of our knowledge, this is the first report documenting detailed neuropsychological data on this rare disease. The case study documents widespread cognitive deficits with greater difficulty with visually based abilities than verbal abilities. Specifically, patients with ECD may present with cognitive difficulties in visual learning and memory, processing speed, visuospatial processing, select areas of executive/frontal systems, letter and semantic verbal fluency, and fine motor dexterity.

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn-/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n=6) and postnatal onset of brain overgrowth (n=19). By analysing head size data from their parents (n=24), we have identified a previously unrecognised KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape, and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated iPSC models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we find that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1 related disorders affecting brain structure, cognitive function, and network integrity.

Contributions of macrostructural and microstructural white matter damage to apathy in people with Alzheimer’s disease

AbstractBackgroundApathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD) that affects patients’ quality of life and prognosis. Previous functional neuroimaging studies have found multiple cerebral alterations suggesting a conceptualisation of apathy as a symptom resulting from a communication breakdown among functional neural networks involved in motivational‐affective processing. To test this hypothesis, this study investigated the association between white matter (WM) structural connectivity and apathy in AD.MethodSixty‐one patients with (AD‐AP) and 61 without apathy (AD‐NA) were identified from the ADNI database and matched for diagnosis, cognitive status, age and education. A group of 61 matched healthy older adults (HOA) was also included. Data on cognitive performance, cerebrospinal fluid (CSF) biomarkers, brain volumes and mean DTI indices of 50 WM tracts were extracted for all participants. Cognitive profiles and volumetric/DTI data were compared across groups using general linear models including sex as a covariate. Post hoc analyses were performed to investigate pair‐wise differences in all outcome measures.ResultBoth patient groups showed widespread cognitive deficits and neural alterations, lower amyloid beta and higher phosphorylated tau CSF levels compared to the HOA group. The direct AD‐AP vs AD‐NA comparison showed no significant differences in CSF biomarkers and MRI outcomes, but the AD‐AP group had more severe neuropsychiatric symptoms, lower scores on the Clock Test – copy and relied more on cues in the Logical Memory test – delayed recall. When the patient groups were compared to the HOA independently, the AD‐AP group had more extensive WM damage: 1) reduced WM and larger WM hyperintensity volume; 2) increased radial diffusivity and reduced fractional anisotropy primarily in the cingulum, superior longitudinal and inferior fronto‐occipital fasciculi and genu of the corpus callosum.ConclusionAD‐AP patients had WM damage mildly more severe than that observed in AD‐NA, especially in associative tracts in the frontal lobes and the cingulum. Such disruption in structural connectivity might affect crucial functional inter‐network communication resulting in motivational deficits and worse cognitive decline. These findings warrant further investigations to ascertain the relationship between WM damage and disruption of functional brain network dynamic interactions in AD patients with apathy.

374 Identification of Psychosis Risk Biomarkers in 22q11DS for future translational studies

OBJECTIVES/GOALS: 22q.11 deletion syndrome (22q11DS) is a genomic syndrome that elevates risk for psychosis >20-fold. We used a battery of cognitive and psychophysiological psychosis-risk biomarkers in 22q11DS patients and healthy subjects in order to identify biomarkers of psychosis in 22q11DS that could be used as translational targets in intervention studies. METHODS/STUDY POPULATION: We recruited 15 22q11DS individuals (Mean age=30, M/F=9/6) and 19 healthy controls (HCs; Mean age=34, M/F=5/14). Each individual completed the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, Second edition (WASI-II) Verbal IQ subtests, and the computerized Wisconsin Card Sorting Task (WCST). To examine auditory EEG responses, each participant completed the 'Double-Deviant' target detection paradigm, which presents a pseudorandom sequence of frequent standard tones and infrequent deviant tones. Mismatch negativity (MMN) metrics were generated from this assessment. Welch's t-tests were completed for neurocognitive variables. One-Way ANOVAs were completed to examine EEG results, with sex entered as a separate factor and age entered as a covariate. RESULTS/ANTICIPATED RESULTS: Significant group differences were found in 8 of the 9 neurocognitive measurements (FDR-adjusted p's< 0.02, average Cohen's d=1.62, average observed power= 0.91) indicating widespread cognitive deficits in 22q11DS subjects across multiple domains. The Double-Deviant MMN ERP response was significantly smaller in absolute magnitude in the 22q11DS group (FDR-adjusted p=0.048, Cohen’s d= -0.864, observed power= 0.58). The MMN ERPs for the frequency and duration deviants were not significantly different (FDR-adjusted p's> 0.33). No group by sex interactions were observed in any of the measures. Neurocognitive variables were associated with psychosis positive, negative, general, and disorganized symptom scales. DISCUSSION/SIGNIFICANCE: Our results identify potential psychosis-risk biomarkers in 22q11DS. If replicated, these biomarkers could provide important translational targets for future clinical trials for individuals with 22q11DS and other individuals at-risk for psychosis syndromes.

“Poor brain development” in the global South? Challenging the science of early childhood interventions

AbstractGlobal Early Childhood Development (ECD)—an applied field with the aim to improve the “brain structure and function” of future generations in the global South—has moved to the center of international development. Global ECD rests heavily on evidence claims about widespread cognitive, social, and emotional deficits in the global South and the benefits of changing parenting practices in order to optimize early childhood development. We challenge these claims on the grounds that the leading ECD literature excludes research from anthropology, cultural psychology, and related fields that could provide crucial insights about childrearing and children's development in the targeted communities. We encourage anthropologists and other scholars with ethnographic expertise on childhood to critically engage with global ECD. To facilitate such an endeavor, this article sketches the history, scientific claims, and interventions of global ECD, points out the critical potential of ethnographic research, and suggests strategies to make ethnography more relevant.

Reorganized Hubs of Brain Functional Networks after Acute Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI)-associated damage to hub regions can lead to disrupted modular structures of functional brain networks and may result in widespread cognitive and behavioral deficits. The spatial layout of brain connections and modules is essential for understanding the reorganization of brain networks to trauma. We investigated the roles of hubs in inter-subnetwork information coordination and integration using participation coefficients (PCs) in 74 patients with acute mTBI and 51 matched healthy controls. In some brain networks, such as default mode network (DMN) and frontoparietal network (FPN), mild TBI patients had decreased PC levels, while this measure was saliently increased in patients in other networks, such as the visual network. The hub disruption index was defined as the gradient of a straight line fitted to scatterplots of individual mTBI in participation coefficient versus mean participation coefficient of healthy groups. There was a trend of radical reorganization of some efficient "hub" nodes in patients (κ = -0.15), compared with controls (κ close to 0). The PC of brain hubs can also differentiate mTBI patients from controls with an 88% accuracy, and decreased PC levels in FPN can predict patient' s worse cognitive information processing speed (r = 0.36, p < 0.002) and working memory performance (r = 0.35, p < 0.002). Reduced PC within the DMN was associated with patients' complaints of post-concussion symptoms (r = -0.35, p < 0.002). This evidence suggests a trend of spatial transition of hub profiles in acute mTBI, and graph metrics of PC measures can be used as potential diagnostic biomarkers.

Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy: A Pilot Study.

Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24–1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.

Posterior Parietal Cortex Dysfunction is Central to Working Memory Storage and Broad Cognitive Deficits in Schizophrenia

Working memory (WM) deficiencies in patients with schizophrenia (PSZ) are thought to be caused by PFC dysfunction, but few research have looked at non-manipulated measures of WM storage. Storage capacity is more closely tied to the posterior parietal cortex (PPC) than the frontal cortex (PFC) in neurotypical people, suggesting that impairments in WM storage capacity in schizophrenia that are associated with widespread cognitive deficits may be related to neuronal activity in the PPC. While receiving fMRI, 37 PSZ and 37 matched healthy control volunteers of both sexes conducted a change detection test with varied set sizes. The assignment was created to emphasis WM storage while requiring minimal top-down management. BOLD activity correlated with the number of items kept in WM (K), as determined by task performance at a particular set size, according to whole-brain analyses. Independent of set size, K values predicted BOLD activity in the PPC, including the superior and inferior parietal lobules, intraparietal sulcus, and middle occipital gyrus, across groups. In the left PPC, whole-brain interaction analysis revealed that PSZ had much less K-dependent signal modulation than healthy control participants, a finding that could not be explained by a smaller K value range. The slope between K and PPC activation accounted for 43.4 percent of the variations in broad cognitive performance across groups. These findings suggest that PPC dysfunction is linked to WM storage abnormalities in PSZ and may play a role in schizophrenia's widespread cognitive deficiencies.

Cognitive Deficits and Their White Matter Correlates in Schizophrenia

Several previous smaller studies have shown that individuals with schizophrenia demonstrate widespread cognitive deficits and that cognitive deficits are among the best predictors of real-world functioning. Here, we combine cognitive, imaging, and clinical data (n = 900) to investigate cognition across the schizophrenia trajectory and to test the associations with clinical variables and white matter.

The relation of depression with structural brain abnormalities and cognitive functioning: the Maastricht study.

Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = -0.18(-0.28;-0.08)], executive functioning & attention [mean difference = -0.13(-0.25;-0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile.

MACHINE LEARNING IN PSYCHIATRIC GENOMICS: INTEGRATING MULTIPLE LEVELS OF ANALYSIS THROUGH DEEP NETWORK MODELS

Schizophrenia patients (SCZ) display widespread cognitive deficits that are strongly associated with functional outcomes. Cognitive impairments occur along a genetic continuum among SCZ, their unaffected first-degree relatives (FRs) and healthy controls (HCs). Although SCZ impairs the premorbid intelligence quotient (IQ) and causes a subsequent intelligence decline (ID), a decrease in present IQ from the premorbid level, it remains unclear when during the illness course these impairments develop. Differences in premorbid and present IQ and ID were investigated among 125 SCZ, 61 FRs and 107 HCs, using analysis of covariance and a paired t-test. Furthermore, these subjects were classified into preserved and deteriorated IQ groups based on the degree of ID, and we investigated which factors contribute to this classification. We found significant differences in premorbid and present IQ among the diagnostic groups. Compared with HCs, SCZ and FRs displayed lower premorbid and present IQ. There was no significant difference in premorbid IQ between SCZ and FRs, but SCZ had a significantly lower present IQ than FRs. Only SCZ showed a significant ID. As most FRs and HCs did not display an ID, there were fewer subjects with deteriorated IQ among FRs and HCs than among SCZ. Subjects with preserved IQ showed higher educational attainment than those with deteriorated IQ among SCZ and FRs. These findings suggest that the impairment of premorbid IQ and the ID in SCZ become evident before and around the time of onset, respectively, and different pathophysiological mechanisms might be related to these impairments.

Intelligence decline between present and premorbid IQ in schizophrenia: Schizophrenia Non-Affected Relative Project (SNARP)

Schizophrenia patients (SCZ) display widespread cognitive deficits that are strongly associated with functional outcomes. Cognitive impairments occur along a genetic continuum among SCZ, their unaffected first-degree relatives (FRs) and healthy controls (HCs). Although SCZ impairs the premorbid intelligence quotient (IQ) and causes a subsequent intelligence decline (ID), a decrease in present IQ from the premorbid level, it remains unclear when during the illness course these impairments develop. Differences in premorbid and present IQ and ID were investigated among 125 SCZ, 61 FRs and 107 HCs, using analysis of covariance and a paired t-test. Furthermore, these subjects were classified into preserved and deteriorated IQ groups based on the degree of ID, and we investigated which factors contribute to this classification. We found significant differences in premorbid and present IQ among the diagnostic groups. Compared with HCs, SCZ and FRs displayed lower premorbid and present IQ. There was no significant difference in premorbid IQ between SCZ and FRs, but SCZ had a significantly lower present IQ than FRs. Only SCZ showed a significant ID. As most FRs and HCs did not display an ID, there were fewer subjects with deteriorated IQ among FRs and HCs than among SCZ. Subjects with preserved IQ showed higher educational attainment than those with deteriorated IQ among SCZ and FRs. These findings suggest that the impairment of premorbid IQ and the ID in SCZ become evident before and around the time of onset, respectively, and different pathophysiological mechanisms might be related to these impairments.

Schizophrenia, cognition, and aging: cognitive deficits and the relationship between test performance and aging

ABSTRACTMost measures of cognitive function decline with age during adulthood. Research indicates that people with schizophrenia experience considerable cognitive deficits. These deficits appear to become more troublesome with increasing age, but this has been debated. The aim of this research was to better understand the age related cognitive deficits of Icelandic subjects with schizophrenia in comparison to healthy individuals. Cognition of individuals 18 to 64 years of age was evaluated with 10 neuropsychological tests. People with schizophrenia performed significantly worse on all tests, as expected, indicating widespread cognitive deficits compared to healthy individuals, independent of age. Furthermore, the results suggest that people with schizophrenia follow a similar age-related trajectory of cognitive decline as healthy individuals. Overall, we conclude that the cognitive difficulties often experienced by older people with schizophrenia are better explained by lower cognitive function at the time of diagnosis than by faster cognitive decline with increasing age.

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene.CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2−/− larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2−/− larval brain.Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC.

Widespread Cognitive Deficits in Alcoholism Persistent Following Prolonged Abstinence: An Updated Meta-analysis of Studies That Used Standardised Neuropsychological Assessment Tools.

This study presents an updated meta-analysis replicating the study of (Stavro, K., Pelletier, J., & Potvin, S. (2013). Widespread and sustained cognitive deficits in alcoholism: A meta-analysis. Addiction Biology, 18, 203-213. doi:10.1111/j.1369-1600.2011.00418.x) regarding the cognitive functioning of alcoholics as a function of time abstinent. A total of 34 studies (including a total of 2,786 participants) that met pre-determined inclusion and exclusion criteria were included in the analyses. The alcoholics were categorised into recently detoxified alcoholics (0-31 days sober), alcoholics 32-365 days sober and alcoholics >365 days sober consistent with the previous study. The current study employed more stringent control on the tests included in the analysis to include only those tasks described in contemporary neuropsychological test compendia. Forty-seven percent of the papers surveyed were not include in the previous meta-analysis. The results indicated that there was a diffuse and pervasive pattern of cognitive deficit among recently detoxified alcoholics and that these deficits, particularly with regard to memory functioning, persisted even in longer term abstinent alcoholics. This was inconsistent with the prior meta-analysis which contended that significant cognitive recovery was possible after as little as 1 year. The persisting cognitive deficits were noted across a wide range of cognitive functions, supporting the notion of a diffuse rather than a specific compromise of cognition in alcoholism following discontinuation, as measured using standardised neuropsychological tests. Limitations on the finding included the fact that it was a cross-sectional rather than a longitudinal analysis, was subject to heterogeneity of method, had low representation of females in the samples, and had fewer studies of long-term sober samples.

Neuropsychological Performance in Alcohol Dependent Patients: A One-Year Longitudinal Study.

ObjectiveDespite several studies that have highlighted the harmful effects of alcohol consumption on cognitive functions it remains unclear whether certain brain areas are more sensitive than others are or whether alcohol causes widespread cognitive deficit. Moreover, the role of continued abstinence has yet to be clarified regarding the quality of recovery on the different cognitive domains. The aim of this 1-year longitudinal study was to evaluate the recovery of cognitive deficits in the medium (6 months) and long term (12 months) after the interruption of drinking.MethodsForty-one alcohol-dependent patients were recruited from two outpatient treatment facilities and cognitive functions were compared on a control group of forty healthy controls. The patients were then re-assessed at 6 and 12 months. Changes in neuropsychological measures were evaluated with repeated measures analysis of variance (ANOVA). We also compared 1-year follow-up scores with control data (unpaired t tests) to identify tests on which significant differences persisted.ResultsPatients performed significantly worse than controls in all cognitive domains investigated and this cognitive impairment was evident in recently abstinent patients. A year of abstinence resulted in a significant improvement in all cognitive domains assessed after detoxification from alcohol. After year 1, alcoholic subjects had returned to normal levels compared to healthy controls on all domains except for general non-verbal intelligence, verbal memory and some visuospatial skills.ConclusionOur results support the hypothesis of widespread impairment resulting from alcohol consumption. The recovery of cognitive functions is not homogeneous during prolonged abstinence.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.

P306 Motor cortex tRNS reduce pain and improve affective and cognitive impairment in patients with fibromyalgia: Preliminary results of a randomized sham-controlled trial

Background Fibromyalgia (FMS) is a clinical syndrome characterized by widespread musculoskeletal pain, chronic fatigue, cognitive deficit, sleep and mood disorders. Most pharmacological therapies showed limited effectiveness and there’s need for new effective and well tolerated therapeutic tools. Recently, transcranial direct-current stimulation (tDCS) of motor cortex showed able to reduce pain, while dorsolateral prefrontal cortex (DLPFC) tDCS improved anxiety, depression and cognitive impairment in FMS. A new application, random noise stimulation (tRNS), using randomly changing alternating currents, showed very recently ability to ameliorate working memory and pain in limited series of FMS and neuropathic pain patients. Here we explored the clinical effects of primary motor cortex (M1) tRNS in FMS patients. Materials and methods Twenty female patients with FMS between the ages of 26 and 67 were randomized into two treatment groups undergoing daily stimulation sessions for two weeks (weekend free): one received active, real tRNS and the other one sham, placebo tRNS. Each patient was evaluated, before and after treatment, through Visual Analogue Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS) and other specific neurophychological tests, such as Trail Making Test (TMT), Rey Auditory Verbal Learning Test (AVLT), Forward and Backward Digit Span, FAS verbal fluency test. Results M1 active tRNS, compared to sham, induced a general improvement of FMS clinical picture: pain, depression, anxiety and FIQ scores showed significant reduction. Even TMT A, AVLT and FAS scores improved significantly. Discussion and conclusions These findings suggest M1 tRNS can be very effective in relieving symptoms of fibromyalgia. Differently from motor cortex tDCS, tRNS seems able to counteract not only pain but also cognitive disturbance in these patients. This could follow to the invoked mechanism of stochastic resonance that would bring to a synchronization of neural firing and so more spreading and lasting effects.

Cognitive dysfunction in bipolar disorder and schizophrenia: a systematic review of meta-analyses.

Cognitive impairment is a core feature of schizophrenia (SZ) and bipolar disorder (BD). A neurocognitive profile characterized by widespread cognitive deficits across multiple domains in the context of substantial intellectual impairment, which appears to antedate illness onset, is a replicated finding in SZ. There is no specific neuropsychological signature that can facilitate the diagnostic differentiation of SZ and BD, notwithstanding, neuropsychological deficits appear more severe in SZ. The literature in this field has provided contradictory results due to methodological differences across studies. Meta-analytic techniques may offer an opportunity to synthesize findings and to control for potential sources of heterogeneity. Here, we performed a systematic review of meta-analyses of neuropsychological findings in SZ and BD. While there is no conclusive evidence for progressive cognitive deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a subgroup of patients with BD may be related to a shared genetically determined influence on neurodevelopment.