Full Neuropsychological Evaluation Research Articles

Development of a prediction model of conversion to Alzheimer’s disease in people with mild cognitive impairment: the statistical analysis plan of the INTERCEPTOR project

BackgroundIn recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer’s disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future. MethodsThe ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50–85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ([18F]FDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1–40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram.DiscussionThis paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions.Trial registrationClinicalTrials.gov NCT03834402. Registered on February 8, 2019

A - 153 Differing Impacts of Divided Auditory and Visual Attention on Abstract Reasoning among Patients with Mild Traumatic Brain Injury.

Although not all mild traumatic brain injuries (mTBIs) lead to long-term effects, they can still have significant cognitive and emotional impacts. One of the common lasting symptoms of mTBI is attentional deficit, with divided attention being specifically negatively impacted by mTBIs. This study investigated the impacts of divided auditory attention and divided visual attention on executive functioning among patients with mTBI. Participants were 98 mTBI patients. Ethnicity was self-identified as 77.5% White, 6.3%, Asian, 2.7% Hispanic, and 13.5% Mixed/Other, gender was 68% women. Tests included the Neuropsychological Assessment Battery (NAB) Numbers & Letters Test to assess divided visual attention, Paced Auditory Serial Addition Task (PASAT) for divided auditory attention, and the Halstead Category Test (HCT) to assess the abstract reasoning domain of executive functioning as part of a full neuropsychological evaluation at a private outpatient clinic. Multiple linear regression was used to analyze the data. The overall model was statistically significant (F(3,94) = 3.23, p = 0.03, R2 = 0.09). Results indicated a significant positive relationship between abstract reasoning and auditory divided attention (β= 2.42, p = 0.03), but no significant relationship between abstract reasoning and visual divided attention (β= 1.5, p = 0.2). The findings of this study suggest that divided auditory and visual attention may impact the abstract reasoning and problem-solving domain of executive functioning differently among those who have sustained mild traumatic brain injury. Specifically, divided auditory attention may play a more significant role in abstract reasoning abilities than visual divided attention.

Electrophysiological and Neuropsychological Indices of Cognitive Dysfunction in Patients with Chronic Insomnia and Severe Benzodiazepine Use Disorder.

Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.

Neuropsychiatric symptoms and functional connectivity of neurotransmitter producing nuclei in MCI and mild dementia in Alzheimer’s disease

AbstractBackgroundThere is evidence that neurotransmitter producing nuclei are impaired in Alzheimer's disease (AD). Recent studies suggest that locus coeruleus and ventral tegmental area, main producers of noradrenaline and dopamine, respectively, are affected before the onset of amyloid‐beta deposition in the entorhinal cortex. Dysfunction of these nuclei seem to contribute especially to the manifestation of neuropsychiatric symptoms (NPS), which tend to aggravate as the disease progresses. As such, we aimed to correlate the functional connectivity (FC) maps of basal nucleus of Meynert (BNM), locus coeruleus (LC) and ventral tegmental area (VTA) to NPS in patients with mild cognitive impairment (MCI) and mild dementia in Alzheimer’s disease.MethodWe analyzed data from 43 subjects with altered amyloid‐beta in the cerebrospinal fluid (23 MCI; 20 mild dementia). Participants underwent rs‐fMRI and full neuropsychological evaluation, including Neuropsychiatric Inventory (NPI). FC maps were generated (UF²C‐toolbox) using the BNM, LC and the VTA as seeds separately. We correlated the NPI syndromes (apathy, hyperactivity, affective syndrome and psychosis) scores with the individual FC maps generated with each seed and group regressing for age and years of education variables (SPM12‐toolbox). The significance level was defined as p<0.05 FWE corrected, with subsequent cluster‐level FDR correction p<0.05. In addition, only anatomical regions with more than 10 voxels were described.ResultSignificant correlations were found exclusively with scores from hyperactivity subsyndrome (agitation, irritability, aberrant motor behavior, euphoria and disinhibition). Regarding right VTA we noticed an increased FC mainly with right and left subcallosal area (volumes 177.92 and 211.68mm³, respectively, Figure 1) and left medial orbital gyrus (volume 162.88). We found a similar pattern in the left VTA (Figure 2) and the right LC (Figure 3), showing increased FC predominantly with right subcallosal area (volumes 151.2 and 91.04mm³, respectively) and left subcallosal area (volumes 110.72 and 97.52mm³, respectively). When looking at BNM FC, there were no between‐group changes that reached statistical significance.ConclusionHyperactivity symptoms in AD correlate to changes in noradrenergic and dopaminergic‐producing nuclei‐FC to subcallosal area/left medial orbital gyrus. These findings may support new research for NPS therapies.

Neuropsychiatric symptoms and functional connectivity of neurotransmitter producing nuclei in MCI and mild dementia in Alzheimer’s disease

AbstractBackgroundThere is evidence that neurotransmitter producing nuclei are impaired in Alzheimer's disease (AD). Recent studies suggest that locus coeruleus and ventral tegmental area, main producers of noradrenaline and dopamine, respectively, are affected before the onset of amyloid‐beta deposition in the entorhinal cortex. Dysfunction of these nuclei seem to contribute especially to the manifestation of neuropsychiatric symptoms (NPS), which tend to aggravate as the disease progresses. As such, we aimed to correlate the functional connectivity (FC) maps of basal nucleus of Meynert (BNM), locus coeruleus (LC) and ventral tegmental area (VTA) to NPS in patients with mild cognitive impairment (MCI) and mild dementia in Alzheimer’s disease.MethodWe analyzed data from 43 subjects with altered amyloid‐beta in the cerebrospinal fluid (23 MCI; 20 mild dementia). Participants underwent rs‐fMRI and full neuropsychological evaluation, including Neuropsychiatric Inventory (NPI). FC maps were generated (UF²C‐toolbox) using the BNM, LC and the VTA as seeds separately. We correlated the NPI syndromes (apathy, hyperactivity, affective syndrome and psychosis) scores with the individual FC maps generated with each seed and group regressing for age and years of education variables (SPM12‐toolbox). The significance level was defined as p<0.05 FWE corrected, with subsequent cluster‐level FDR correction p<0.05. In addition, only anatomical regions with more than 10 voxels were described.ResultSignificant correlations were found exclusively with scores from hyperactivity subsyndrome (agitation, irritability, aberrant motor behavior, euphoria and disinhibition). Regarding right VTA we noticed an increased FC mainly with right and left subcallosal area (volumes 177.92 and 211.68mm³, respectively, Figure 1) and left medial orbital gyrus (volume 162.88). We found a similar pattern in the left VTA (Figure 2) and the right LC (Figure 3), showing increased FC predominantly with right subcallosal area (volumes 151.2 and 91.04mm³, respectively) and left subcallosal area (volumes 110.72 and 97.52mm³, respectively). When looking at BNM FC, there were no between‐group changes that reached statistical significance.ConclusionHyperactivity symptoms in AD correlate to changes in noradrenergic and dopaminergic‐producing nuclei‐FC to subcallosal area/left medial orbital gyrus. These findings may support new research for NPS therapies.

Brain structural and functional anomalies associated with simultanagnosia in patients with posterior cortical atrophy

Simultanagnosia is a common symptom of posterior cortical atrophy, and its association with brain structural and functional changes remains unclear. In our study, 18 posterior cortical atrophy patients with simultanagnosia, 29 patients with Alzheimer’s disease and 20 cognitively normal controls were recruited and subjected to full neuropsychological evaluation, including simultanagnosia tests, and structural and resting-state functional MRI. The gray matter volume was assessed by voxel-based morphometry, while the intrinsic functional connectivity was evaluated using the reduced gray matter volume regions of interest as the seed. In contrast to the patients with Alzheimer’s disease, those with posterior cortical atrophy showed the following: (1) markedly lower simultanagnosia test scores, (2) an altered regional gray matter volume of the left middle occipital gyrus and ventral occipital areas, and (3) lowered intrinsic functional connectivity with the left middle occipital gyrus, left lingual gyrus and right middle occipital gyrus separately. Additionally, the gray matter volume of the left middle occipital gyrus and left inferior occipital gyrus were each correlated with simultanagnosia in posterior cortical atrophy patients. The intrinsic functional connectivity of the left middle occipital gyrus with the right superior occipital gyrus and that of the right middle occipital gyrus with the left superior parietal gyrus were also correlated with simultanagnosia in posterior cortical atrophy patients. In summary, this study indicated that simultanagnosia is associated with gray matter reductions and decreased functional connectivity in the left middle occipital gyrus and the left inferior occipital gyrus in patients with posterior cortical atrophy.

Olfaction in patients with Parkinson\u2019s disease: a new threshold test analysis through turning points trajectories

Olfactory deficit is a widely documented non-motor symptom in Parkinson’s disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition. Sixty healthy subjects served as controls. Patients and controls underwent a comprehensive olfactory evaluation with the Sniffin’ Sticks extended test assessing threshold, discrimination and identification and a full neuropsychological evaluation. Besides, threshold test data were analyzed examining all the turning points trajectories. PD patients showed a different olfactory threshold test pattern, i.e., faster olfactory adaptation, than controls with no effect of age. Normosmic PD patients showed different olfactory threshold test pattern, i.e., better threshold score, than normosmic controls. Visuospatial dysfunction was the only factor that significantly influenced this pattern. Olfactory threshold trajectories suggested a possible adaptation phenomenon in PD patients. Our data offered some new insights on normosmic PD patients, which appear to be a subset with a specific psychophysical profile. The analysis of the turning points trajectories, through an olfactory threshold test, could offer additional information on olfactory function in PD patients. Future larger studies should confirm these preliminary findings.

Mediterranean diet and risk for dementia and cognitive decline in a Mediterranean population.

Current evidence suggests that nutrition in general and specific dietary patterns in particular, such as the Mediterranean type diet (MeDi), can be employed as potential preventive strategies against the development of dementia and cognitive decline. However, longitudinal data exploring the applicability of these findings in populations of Mediterranean origin are limited. The aim of the present study was to explore the potential relationships of MeDi adherence with dementia incidence rates and cognitive change over time in a traditional Mediterranean population, characterized by a lifelong exposure to Mediterranean eating habits and lifestyle. The sample consisted of 1046 non-demented individuals over the age of 64 (mean age=73.1; SD=5.0), with available baseline dietary information and longitudinal follow-up. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a global cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. A total of 62 incident dementia cases occurred during a mean (SD) of 3.1 (0.9) years of follow-up. Individuals in the highest MeDi quartile (highest adherence to MeDi) had a 72% lower risk for development of dementia, compared to those in the lowest one (p= 0.013). In addition, analysis of cognitive performance as a function of MeDi score revealed that the biennial cognitive benefit of a 10-unit increase in MeDi score offsets the cognitive decline associated with 1year of cognitive aging. In the present study, higher adherence to MeDi was associated with a reduced risk for dementia and cognitive decline in a traditional Mediterranean population.

Incidence of mild cognitive impairment in the elderly population in Greece: results from the HELIAD study.

There are no published data on Mild Cognitive Impairment (MCI) incidence in people over 65years of age in Greece, relevant literature is scarce for Southern Europe, and reported rates worldwide show great variability. To investigate the incidence and risk factors of MCI and its subtypes in the elderly population in Greece. The incidence cohort of the HELIAD study (Hellenic Epidemiological Longitudinal Investigation of Aging and Diet) comprised 955 individuals who received full neurological and neuropsychological evaluation on two separate occasions about three years apart. The MCI incidence rate in our cohort is 54.07 new cases per 1000 person-years, standardized by age and sex to 59.99. Each additional year of age over 65 raises the probability of novel MCI by 6.2%, while lower educational attainment more than doubles the risk for incident MCI. Apolipoprotein E-ε4 (APOE-ε4) carriage results in increased risk for MCI by more than 1.7 times. Incidence rates for amnestic MCI are slightly higher than for the non-amnestic subtype, and AD is the most common potential underlying etiology. The MCI incidence rate in the Greek population over 65years of age is 54/1000 person-years. Advanced age and APOE-ε4 carriage are predisposing factors, while higher educational attainment was found to exert a protective effect. MCI incidence in people over 65years-old in Greece is consistent with reported rates around the world. Larger studies encompassing neuroimaging and cerebrospinal fluid biomarkers will hopefully shed more light on MCI epidemiology in Greece in the future.

Cerebral amyloid deposition correlates with objectively measured sleep dysfunction

AbstractBackgroundSleep and circadian problems are known to be common along the Alzheimer’s disease (AD) spectrum. Previous research correlated an increase in CSF Aβ with poor sleep quality through self‐reported questionnaires in cognitively unimpaired (CU) individuals. Research on AD patients however showed an increase in tau‐PET. Today, there is increasing evidence that sleep disturbances are an early marker for AD pathology and marker of future risk of cognitive impairment. Our main objective was to study the relationship between sleep efficiency as assessed with polysomnography and amyloid, tau and neuroinflammation.Method28 individuals (21 CU and 7 mild cognitive impairment (MCI)) underwent a [18F]AZD4694 amyloid‐PET scan, [18F]MK6240 tau‐PET scan, [11C]PBR28 neuroinflammation‐PET scan, an MRI a full neuropsychological evaluation as well as a polysomnography. [18F]AZD4694, [18F]MK6240 and [11C]PBR28 standardized uptake value ratios (SUVRs) used the cerebellum grey matter as the reference region and were calculated between 40‐70 min, 90‐110 min and 0‐90 min post‐injection respectively. A voxel based regression model evaluated the relationship between the different pathophysiologies of AD, amyloid, tau and neuroinflammation, and sleep efficiency. The model’s covariates were age and diagnosis.ResultWe found a negative correlation between sleep efficiency as measured with a polysomnography and amyloid. The most impacted regions were the temporal poles, the inferior parietal cortex and subcortical regions such as the thalamus. However, we did not find a correlation with [18F]MK6240 and [11C]PBR28. When we corrected for apnea‐hypopnea index, sex and years of education, results were similar.ConclusionThese preliminary results show that poor sleep quality correlates with amyloid deposition in the brain of CU and MCI individuals. The regions impacted have been related to sleep regulation, such as the thalamus. They are also known to be vulnerable to AD pathophysiology, for example, temporal and inferior parietal cortices. Our study adds to previous research by identifying anatomical correlates, and also using objective assessment of sleep quality. It also corroborates with the idea that sleep deprivation promote Aβ deposition.

Neuroinflammation is associated with non‐REM sleep reduction in individuals without dementia

AbstractBackgroundSleep disturbances and especially reduction of non‐REM (NREM) sleep are common in aging with accumulating evidence showing it might contribute to cognitive decline as well as increase the risk of developing dementia due to Alzheimer’s disease (AD). Lately, sleep disturbances and AD separately have been linked to increase in systemic inflammation. NREM sleep is thought to allow clearance of extracellular Aβ, which led to studies suggesting NREM could be an early biomarker of AD risk. The main objective of this study was to see the relationship between NREM sleep as assessed with polysomnography and neuroinflammation in vivo.Method25 individuals (18 cognitively unimpaired (CU) and 7 mild cognitive impairment (MCI)) underwent a [11C]PBR28 neuroinflammation‐PET scan, an MRI a full neuropsychological evaluation as well as a polysomnography. [11C]PBR28 standardized uptake value ratios (SUVRs) used the cerebellum grey matter as the reference region and was calculated between 0‐90 min post‐injection. A voxel based regression model evaluated the relationship between neuroinflammation as assessed by PET, and the total minutes of NREM sleep. The model’s covariates were age and diagnosis.ResultWe found a negative correlation between neuroinflammation and the total minutes of non‐REM sleep measured by a polysomnography. The regions showing neuroinflammation were the reticular formation, the arcuate nucleus of the medulla, the frontal cortex and especially the vmPFC as well as the insula and temporal poles. When we corrected for sex and years of education, results were similar.ConclusionThese preliminary results show that less NREM sleep correlates with neuroinflammation, in the brain of CU and MCI individuals. The regions impacted, such as the reticular formation, the vmPFC and the insula are needed for arousal and alertness. The arcuate nucleus of the medulla is required for proper breathing. Finally, temporal poles are part of the first regions affected in AD, and later on in the disease, the medial frontal cortex also starts degrading. Our study adds to previous research showing a link between sleep disturbances and neuroinflammation in vivo and identifies anatomical correlates.

Development of an innovative adult attention-deficit hyperactivity disorder clinic.

Pharmacist-psychiatrist collaborative clinic models in specialty mental health clinics are limited, and there has been only 1 report of a clinic focused on adult attention-deficit hyperactivity disorder (ADHD). In this article, we describe the successful implementation of a pharmacist-psychiatrist collaborative practice agreement in an adult ADHD clinic at an academic medical center. Adult patients diagnosed with ADHD after a comprehensive assessment, including a full neuropsychological evaluation, were enrolled in the collaborative treatment clinic. The collaboration was a partnership between a psychiatry department and a school of pharmacy at a public university. We report the details of 58 patients and 774 patient encounters at the collaborative pharmacist-psychiatrist practice from March 2015 through June 2018. The visits were billed using traditional medical billing codes for follow-up visits. Pharmacist practice opportunities included psychiatric evaluation, medication management, counseling, and referral to auxiliary services. Challenges to the clinic's success included limited pharmacist time, prescriptive authority, and reimbursement for services from payors. A collaborative practice model targeted at adult ADHD patients may be a unique clinic setting for psychiatric pharmacists.

An interdisciplinary approach to the screening, diagnosis, and treatment of OEF/OIF Veterans with mild traumatic brain injury

Objective To implement an Integrated TBI Screening Clinic (ITSC) during the mandatory TBI evaluation process at the Department of Veterans Affairs. Referral outcomes were examined regarding Veterans who were determined to need a full neuropsychological evaluation versus those for whom mental health treatment was clinically indicated. Correlations among cognitive measures, posttraumatic stress disorder (PTSD), anxiety, depression, and insomnia symptoms were also examined. Method This study was a retrospective chart review study that included 138 Veterans seen between 2011 and 2014 in a post-deployment primary care clinic. Descriptive statistics and correlations were completed using the: screening Module of the Neuropsychological Assessment Battery (S-NAB), PTSD Checklist-Military version (PCL-M), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Insomnia Severity Index (ISI). Results 19.8% of Veterans required a referral for a full neuropsychological exam and 72.7% were referred for additional mental health services (with some Veterans being referred to both). Significant correlations were found among higher PTSD, depression, anxiety symptoms, with poorer attention and memory (all p < .05). Only PTSD was significantly correlated with poorer executive functioning (r = 0.19, p < .05). Conclusion Integration of a multidisciplinary neuropsychological screening exam during a primary care visit with OEF/OIF Veterans may assist in better delineating symptoms.

Quality of the caregiving relationship and quality of life in mild Alzheimer's dementia.

The present study aims to investigate the quality of the dyadic relationship between mild Alzheimer patients and their caregivers. The main objective is to evaluate the consistency, agreement and validity of the German version of the Scale for Quality of the Current Relationship in Caregiving (SQCRC). The secondary objective was to examine the association of relationship quality with quality of life (QOL) in patients with mild Alzheimer's disease (AD) and their caregivers. In this study, a sample of 50 patients diagnosed with mild AD and their primary caregivers were included. Participants underwent a full neuropsychological evaluation. The quality of the relationship between persons with AD and their caregivers was assessed using the SQCRC. Furthermore, other scales of relationship quality, well-being of the person with AD, and well-being of the caregiver were used. The results showed that the SQCRC has a good internal consistency and high validity. Also, relationship quality as rated by the AD patients (r = 0.37, P < 0.1) and their caregivers (r = 0.51, P < 0.1) was significantly correlated with QOL. The findings suggest that many persons with mild AD can rate their relationship quality and that the patient's self-rated relationship quality is a substantial predictor of their QOL.

Reliability and Validity of the Chinese Version of the Mild Behavioral Impairment Checklist for Screening for Alzheimer's Disease.

The Mild Behavioral Impairment Checklist (MBI-C), a screening scale for neuropsychiatric symptom evaluation, facilitates Alzheimer's disease (AD) screening. However, its validity and reliability for use as an AD screening tool have not been determined. To develop an AD screening scale suitable for the Chinese population. The MBI-C was translated into Chinese and back-translated with the original author's consent. Forty-six AD patients, attending the Xuanwu hospital memory clinic, and 50 sex- and education-matched controls from the community underwent a full neuropsychological evaluation, including MBI-C assessment. Among them, 15 AD patients were evaluated repeatedly, and eight were evaluated simultaneously by two different clinicians, to assess MBI-C reliability. The MBI-C demonstrated good internal consistency reliability, test-retest reliability, and inter-rater reliability. Its optimal cutoff point was 6/7 for identifying AD dementia, with a sensitivity of 86.96% and specificity of 86.00%, and its detection rate for moderate-severe AD dementia was higher than that of the Neuropsychiatric Inventory Questionnaire (NPI-Q). Pearson's correlation coefficients ranged from 0.702 to 0.831, indicating content validity. Seven factors were extracted during principal component analysis, with a cumulative contribution of 70.55%. Moreover, the Pearson's correlation coefficient was 0.758, indicating its criterion validity. The MBI-C could also distinguish AD dementia severity. MBI-C scores were significantly negatively correlated with MMSE and MoCA scores, and positively correlated with ADL scores. This study showed that the Chinese version of MBI-C has high reliability and validity, and could replace the NPI-Q for AD dementia screening in the Chinese population.

A neuropsychological and behavioral study of PLS

Background: Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by progressive degeneration of upper motor neurons, resulting in spasticity and disability. There is, however, mounting evidence that the disease is not limited to upper motor neurons alone and that cognitive and behavioral changes within the spectrum of frontotemporal dementia (FTD) are part of the clinical phenotype. Objectives: To provide an in-depth classification of the cognitive and behavioral profiles of PLS by using the golden standard, a full neuropsychological evaluation, as well as a comprehensive behavioral assessment in a cohort of 30 cases. Results: Only 7 out of 30 PLS patients scored within normal range on all of the tests within our battery. The neuropsychological profile of PLS consists of deficits in social cognition (affective theory of mind (ToM) in particular), fluency, executive functions and memory. Using the revised Strong criteria, we could classify 57% of patients within the FTD spectrum (of which 17% had behavioral variant FTD). An additional 20% of patients had deficits which were not characteristic of FTD. Conclusions: This study confirms that PLS is not a restricted phenotype (only affecting upper motor neurons) and that behavioral and cognitive changes are common. Therefore, clinicians treating PLS patients should routinely assess cognition and behavior as part of routine care as cognitive and behavioral changes impact management, decision-making and care-giver burden. This assessment should be sensitive to the neuropsychological profile of PLS (social cognition (affective ToM in particular), fluency, executive functions and memory) and behavioral changes.

Monitoring neurocognitive functioning in childhood cancer survivors: evaluation of CogState computerized assessment and the Behavior Rating Inventory of Executive Function (BRIEF)

BackgroundMany childhood cancer survivors develop neurocognitive impairment, negatively affecting education and psychosocial functioning. Recommended comprehensive neuropsychological testing can be time- and cost- intensive for both institutions and patients and their families. It is important to find quick and easily administered surveillance measures to identify those in need of evaluation.MethodsWe evaluated, individually and in combination, the sensitivity and specificity of the 1) Behavior Rating Inventory of Executive Functioning-Metacognition Index (BRIEF-MCI), and 2) CogState Composite Index (computerized assessment of cognition) in identifying below grade-level performance on state-administered tests of reading and mathematics among childhood cancer survivors.ResultsThe 45 participants (39% female) were a mean age of 7.1 ± 4.4 years at diagnosis, 14.0 ± 3.0 at evaluation, with a history of leukemia (58%), lymphoma (9%), central nervous system tumors (20%), and other tumors (13%). Impairment on the BRIEF-MCI was associated with low sensitivity (26% reading, 41% mathematics) but stronger specificity (88% reading, 96% mathematics). We found similar associations for the CogState Composite Index with sensitivity of 26% for reading and 29% for mathematics and specificity of 92% for both reading and mathematics. Combining the two measures did not improve sensitivity appreciably (47% reading, 59% mathematics) while reducing specificity (84% reading, 88% mathematics).ConclusionsWhile individuals identified from the BRIEF-MCI or CogState Composite would likely benefit from a full neuropsychological evaluation given the strong specificity, use of these measures as screening tools is limited. With poor sensitivity, they do not identify many patients with academic difficulties and in need of a full neuropsychological evaluation. Continued effort is required to find screening measures that have both strong sensitivity and specificity.

Sleep quality mediates the relationship between frailty and cognitive dysfunction in non-demented middle aged to older adults.

154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included. Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures. Frailty severity predicted weaker executive function (B = -2.77, β = -0.30, 95% CI = -4.05 - -1.29) and processing speed (B = -1.57, β = -0.17, 95% CI = -3.10 - -0.16). Poor sleep quality predicted poorer executive function (B = -0.47, β = -0.21, 95% CI = -0.79 - -0.08), processing speed (B = -0.64, β = -0.28, 95% CI = -0.98 - -0.31), learning (B = -0.42, β = -0.19, 95% CI = -0.76 - -0.05) and delayed recall (B = -0.41, β = -0.16, 95% CI = -0.80 - -0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = -0.66, β = -0.07, 95% CI = -1.48 - -0.39), learning (B = -0.85, β = -0.07, 95% CI = -1.85 - -0.12), delayed recall (B = -0.47, β = -0.08, 95% CI = -2.12 - -0.39) and processing speed (B = -0.90, β = -0.09, 95% CI = -1.85 - -0.20). Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.

Dementia Prevalence in Greece: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated. We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions. Our sample comprised 1792 adults 65 years of age or older, who received a full neurological and neuropsychological evaluation that led to a consensus diagnosis. The overall prevalence of dementia was 5.0%, with 75.3% of the cases attributed to Alzheimer disease. Dementia odds were 15.8% higher for every year of advancing age and 9.4% lower for every additional year of education. Carrying at least 1 APOE-ε4 allele doubled the risk of dementia, whereas sex did not exert a statistically significant effect. Our results are consistent with previous research in Southern European countries; dementia prevalence in Greece is in the lower range of what has been reported globally.

O9.4. PREDICTING SCHIZOPHRENIA: IDENTIFICATION OF MULTIMODAL MARKERS OF DISEASE THROUGH A MACHINE LEARNING APPROACH

BackgroundDiagnosis of schizophrenia is based on a collection of symptoms which are heterogeneous from one patient to the other. Therefore, improving the reliability of this diagnosis is a currently unmet need. Schizophrenia risk is associated with genetic variation and with environmental factors potentially affecting neurodevelopment. Moreover, among the symptoms, cognitive abnormalities are heritable and predate its clinical onset.Multivariate techniques can leverage the high dimensionality of data in order to study the combined effect of multiple risk factors and symptoms on clinical predictions. The aim of the current study is therefore to assess the predictability of schizophrenia diagnosis applying machine learning techniques to an ensemble of genetic, early environmental and cognitive deficits variables.Methods442 subjects (339 healthy controls – HC – and 103 patients with schizophrenia – SCZ) were recruited for the study. Participants underwent a full neuropsychological evaluation (Modality 1, assessment of working memory, verbal fluency, intelligence quotient, attention, speed of processing and cognitive control), a broad environmental assessment (Modality 2, investigation of urbanicity, obstetric complications, developmental anomalies, socio-economic parental status and age of parents at birth) and genome-wide genotyping (Modality 3). Following published procedures, we computed individual risk scores for each of the single nucleotide polymorphisms (SNPs) associated with risk for schizophrenia in the Psychiatric Genomics Consortium (PGC) study. Data from Modalities 1, 2 and 3 entered NeuroMiner v0.998 and underwent preprocessing procedures through scaling, pruning of non-informative variables and imputation of missing values through Euclidean distance-based nearest-neighbor search. Then, these three modalities were included in a Support Vector Machine HC vs. SCZ classification algorithm, which applied decision-based data fusion strategies to integrate the individual predictions of the three modalities in a nested cross-validation framework.ResultsOur cross-validated results revealed that Modality 1 (cognition) predicted schizophrenia diagnosis with the highest Balanced Accuracy (BAC, 87.3%) and that the most selected cognitive indices were intelligence quotient scores and attentional abilities. Modality 2 (environment) classified HC and SCZ with a BAC of 67.2%, and the most predictive environmental features were the parental socio-economic status, the presence of developmental anomalies during the first year of life and the age of father at birth. On the other hand, Modality 3 (genetics) predicted schizophrenia diagnosis with BAC=54,1%. The most informative SNPs were FUT9 rs117074560, TCF4 rs72934570 and STAG1 rs7432375. Decision-based fusion combining individual cognitive, environmental and genetic decision scores predicted the classification of SCZ from HC with a 78.9% BAC.DiscussionOur results using a novel machine learning approach suggest that an ensemble of cognitive, early environmental and genetic features can predict schizophrenia with significant accuracy. Our results also give key information on cognitive and environmental factors that can be targeted in early identification programs and offer novel insights about genetic loci that may be prioritized in future investigations of the pathophysiology of the disease. However, the near chance-level predictive ability of the genetic modality alone calls for the implementation and testing of more complex models of interaction between multiple risk factors.