Detailed Neuropsychological Assessment Research Articles

Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study.

Diabetic subjects are at increased risk of subtle cognitive impairment since the disease early stages and of dementia later in life. In animal models, glucagon-like peptide-1 receptor agonizts (GLP1-RAs) have been shown to exert neuroprotective effects, expecially in the memory domain. We assessed whether treatment with a GLP1-RA might affect cognitive functions in type 2 diabetic subjects independently on the weight loss it might induce. Forty metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes mellitus, received liraglutide (1.8 mg/d) (n = 20) or lifestyle counseling (dietary intervention and exercise training) (n = 20) until achieving a modest and comparable weight loss (-7% of initial body weight). A detailed neuropsychological assessment before and after weight loss was completed in 16 patients per arm, who were administered a total of seven psychological tests, thus assessing three composite domain z-scores for attention, memory, and executive control. After comparable weight loss and superimposable glycemic control and insulin sensitivity, a significant increase in short term memory (mean Digit Span Z score from -0.06 to 0.80, p = 0.024) and memory composite z-score (mean memory z-score from -0.67 to 0.032, p = 0.0065) was observed in the liraglutide exposed subjects (between group p = 0.041 and p = 0.033, respectively). Liraglutide might slow down memory function decline in diabetic patients in early, and possibly preclinical stages of the disease.

Korean Traditional Medicine in Treating Patients with Mild Cognitive Impairment: A Multicenter Prospective Observational Case Series.

In Korea, patients with mild cognitive impairment can choose to receive treatment of Korean medicine, and Korean medicine hospitals provide specialized medical care for the prevention and management of cognitive disorders. The aim of the study is to explore the role of Korean medicine therapy for patients with mild cognitive impairment in a real clinical setting. Fifteen patients with amnestic mild cognitive impairment were enrolled in this prospective observational study in three Korean medicine hospitals. Korean medicine treatments were delivered by experienced professionals and not restricted to standardized treatment. Outcome measures were prospectively planned to examine the Korean-Montreal Cognitive Assessment (K-MoCA), Korean-Mini Mental State Examination (K-MMSE), and other detailed neuropsychological assessment at the baseline and after 12 and 24 weeks of treatment. Korean medicine treatment for MCI treatment in the real-world clinical setting included herbal medicine and acupuncture. The most frequently used herbs in herbal decoctions were Acori Graminei Rhizoma, Polygalae Radix, and Poria Sclerotium Cum Pini Radix. The herbal medicine formulae used in this study were classified into three categories: tonifying Qi (33.3%), tonifying kidney (46.7%), and calming liver (20%) formulae. In the cognitive ability assessment, the K-MoCA score significantly improved after treatment (mean difference 2.6; 95% CI: 1.3 to 3.9, p=0.001). The K-MMSE score slightly increased after treatment; however, the improvement was not statistically significant (mean difference 0.8; 95% CI: −0.5 to 2.0, p=0.195). In detailed neuropsychological assessment, the cognitive domains of executive functions and memory after the treatment were distinctively improved. In this prospective observational case series, we could see the real clinical environments of treating patients with mild cognitive impairment in Korean medicine hospitals. Patients treated with Korean medicine showed improved results in the neuropsychological assessment after 12 and 24 weeks.

Longitudinal trajectories of amyloid deposition, cortical thickness, and tau in Down syndrome: A deep-phenotyping case report

IntroductionComorbid Alzheimer disease pathologies are frequently found in people with Down syndrome (DS). We report a deep phenotyping study undertaken over 7 years in a participant with DS who was nondemented at baseline but developed dementia after 5 years. MethodsThroughout the course of the study, the participant was seen 4 times (2010, 2013, 2015, and 2017). Multimodal neuroimaging, including three serial scans of [11C]-PiB-PET, four structural magnetic resonance imagings, as well as a [18F]-AV1451 scan, was interpreted alongside detailed neuropsychological assessments over the study period. ResultsAmyloid beta accumulation preceded the onset of dementia and cognitive decline, which in turn corresponded to the predominant deposition of tau in temporoparietal cortices. DiscussionUntil now, data on the longitudinal trajectories of amyloid accumulation, tau pathology, and brain atrophy over multiple time points remain scarce in DS. This case report highlights the potential for deep phenotyping imaging to elucidate the substrates of cognitive decline in DS, although further longitudinal studies are necessary to clarify the relative contributions of both amyloid and tau.

The longitudinal evaluation of familial frontotemporal dementia subjects protocol: Framework and methodology

IntroductionIt is important to establish the natural history of familial frontotemporal lobar degeneration (f-FTLD) and provide clinical and biomarker data for planning these studies, particularly in the asymptomatic phase. MethodsThe Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects protocol was designed to enroll and follow at least 300 subjects for more than at least three annual visits who are members of kindreds with a mutation in one of the three most common f-FTLD genes—microtubule-associated protein tau, progranulin, or chromosome 9 open reading frame 72. ResultsWe present the theoretical considerations of f-FTLD and the aims/objectives of this protocol. We also describe the design and methodology for evaluating and rating subjects, in which detailed clinical and neuropsychological assessments are performed, biofluid samples are collected, and magnetic resonance imaging scans are performed using a standard protocol. DiscussionThese data and samples, which are available to interested investigators worldwide, will facilitate planning for upcoming disease-modifying therapeutic trials in f-FTLD.

Specific cognitive deficits in preschool age correlated with qualitative and quantitative MRI parameters in prematurely born children

Cognitive deficits after perinatal brain lesion in preterm infants are among the most common neurodevelopmental disturbances. The relationship between structural changes on at term magnetic resonance imaging (MRI) and cognitive deficits in the preschool age should be a special focus due to timely intervention. The aim of this study was to correlate qualitative and quantitative MRI parameters of perinatal brain lesion in preterm children, on early neonatal MRI and follow up MRI, with general and specific cognitive functions in the preschool age. Twenty-one preterm infants with verified perinatal lesions based on clinical and ultrasound data underwent a brain MRI at term-equivalent age and a second MRI between 3 and 5 years of age. Qualitative and quantitative MRI analyses were done. All subjects underwent cognitive assessment (3-5 years) using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Developmental Neuropsychological Assessment (NEPSY-II). Results show that many structural changes on at term MRI and on follow up MRI in preterm born children moderately correlate with specific cognitive deficits in preschool age. At term equivalent MRI, white matter changes and cortical thickness correlate to general and specific cognitive functions in infants born preterm. By analyzing follow up MRI at preschool age, structural changes of different white matter segments, corpus callosum, cortical thickness and lobe volume correlate to some specific cognitive functions. Besides general cognitive delay, specific cognitive deficits in preterm children should be targeted in research and intervention, optimally combined with MRI scanning, providing timely and early intervention of cognitive deficits after perinatal brain lesion. Our results, as well as previously published results, suggest the importance of detailed preschool neuropsychological assessment, prior to enrolment in the school system. Although preliminary, our results expand our understanding of the relationship between early brain developmental lesions and cognitive outcome following premature birth.

Effects of orthostatic hypotension on cognition in type 2 diabetes mellitus.

To evaluate the effect of a decrease in blood pressure (BP) fulfilling the diagnostic criteria for orthostatic hypotension (OH) on performance in each domain of cognitive function in patients with type 2 diabetes mellitus using a cross-sectional and within-group design. Subjects were individuals without dementia and with type 2 diabetes mellitus, including 107 individuals without OH and 94 with OH (DMOH); 95 control participants were also included. BP was assessed in both the supine and standing positions. A detailed neuropsychological assessment was made in each posture for all subjects. There were statistically significant differences between the patients without OH and the DMOH group with regard to some cognitive measures while supine. Standing posture exacerbated and broadened cognitive deficits in the DMOH group for all measures in the different domains of cognition including executive functioning, memory, visuospatial skills, information processing speed, and attention. When group-specific supine scores were used as baseline anchors, both the patients without OH and the DMOH group showed cognitive changes when transitioning from a supine to a standing, upright position, with the DMOH group exhibiting a wider range of neuropsychological deficits in memory, visuospatial skills, executive function, and sustained attention, as well as significant changes in information processing speed. These data demonstrate that type 2 diabetes mellitus patients with OH had transient, posture-mediated cognitive deficits in excess of those found in diabetes mellitus without OH. Understanding the effects of OH on cognition due to autonomic failure is important, particularly as clinical assessments and neuroimaging collect data only in the seated or supine positions. ANN NEUROL 2019;86:754-761.

Association Between Carotid Artery Intima-Media Thickness and Combinations of Mild Cognitive Impairment and Pre-Frailty in Older Adults.

Carotid intima-media thickness (CIMT) has been proposed as a surrogate marker of cardiovascular disease. Mild cognitive impairment (MCI) and pre-frailty are reportedly associated with increased CIMT. As the evidence on the association of CIMT with combinations of MCI and pre-frailty is limited, this association is examined. A total of 231 older adults participated. MCI was defined according to clinical consensus or psychometric criteria by a dementia specialist, and considering detailed neuropsychological assessments. Also, pre-frailty was defined as subjects with frail component of 1 or 2. Carotid variables were measured using a B-mode ultrasound. The analysis of covariance (ANCOVA) was performed to assess independent differences in CIMT among the four groups, according to the cognitive function and frailty status after a multivariate adjustment. Increased CIMT is associated with combinations of MCI and pre-frailty. ANCOVA showed that CIMTs were significantly different among the four groups according to the cognitive function and frailty status. CIMTmax combined with MCI and pre-frailty was the thickest (1.04 ± 0.3 mm), whereas the CIMT of no MCI and no pre-frailty was the thinnest (0.82 ± 0.2 mm). The results suggest that combinations of MCI and pre-frailty are associated with increased CIMT in older adults.

Cerebrospinal Fluid Markers of Synaptic Injury and Functional Connectivity in Alzheimer Disease: Protocol for a Cross-Sectional Study.

BackgroundSynaptic loss is the best surrogate for cognitive decline in Alzheimer disease (AD) and is more closely associated with cognitive function than amyloid or tau pathologies. Neurogranin (Ng) and synaptosome–associated protein-25 (SNAP-25) have demonstrated utility as cerebrospinal fluid (CSF) markers of synaptic injury in presymptomatic and symptomatic AD. While these synaptic markers have been shown to correlate with cognitive impairment and whole brain or regional atrophy in previous studies of AD, to our knowledge, the relationship between fluid markers of synaptic injury and functional brain imaging has not been previously investigated.ObjectiveThe main objective of this study is to examine the relationship between CSF markers of synaptic injury (Ng and SNAP-25) and functional connectivity (FC) in the default mode and semantic memory networks in individuals with mild cognitive impairment (MCI) and mild dementia due to AD (Clinical Dementia Rating [CDR] 0.5-1) and cognitively normal controls (CDR 0), adjusting for age, gender, and the apolipoprotein E4 (APOE4) genotype. Secondary objectives include investigating the associations between CSF markers of amyloid and tau pathology (CSF tau, p-tau181, and Aβ42) and FC in the default mode and semantic memory networks in AD (CDR 0.5-1) and controls (CDR 0), adjusting for age, gender, and the APOE4 genotype.MethodsThis is a cross-sectional study of individuals with MCI or mild dementia due to AD (CDR 0.5-1; n=20), and cognitively normal controls (CDR 0; n=20). Participants will undergo detailed clinical and neuropsychological assessments, CSF biomarker assessments (CSF Ng, SNAP-25, tau, p-tau181, and Aβ42 levels) and functional magnetic resonance imaging assessments, using a Siemens 3.0 Tesla Prisma scanner, during resting state and during the performance of a semantic memory task. All study procedures will be completed within 4 months of enrollment. Partial correlation analyses will examine associations of CSF biomarker measures with FC in the default mode and semantic memory networks in AD and controls.ResultsThis study was funded by the Chronic Brain Injury Discovery Themes of the Ohio State University College of Medicine. Study enrollment began in April 2018. Study procedures and data analysis are currently underway. Results are expected by December 2019.ConclusionsFindings from this study will further support the utility of CSF Ng and SNAP-25 as markers of synaptic injury by examining their associations with functional alterations in cortical networks affected by early AD pathology.International Registered Report Identifier (IRRID)DERR1-10.2196/14302

Transcranial magnetic stimulation improves cognition over time in Parkinson's disease

IntroductionCognitive impairment can occur in the early phase of Parkinson's disease and increases the risk of developing dementia. Cognitive deficits were shown to be associated with functional alterations in the dorsolateral prefrontal cortex (DLPFC) and caudate nucleus. Two previous transcranial magnetic stimulation studies over the left DLPFC showed short-term improvement in cognitive performance and focused on specific task. Methods28 patients with idiopathic Parkinson's disease and mild cognitive impairment received intermittent “theta burst” stimulation (iTBS) (active, N = 14; or sham, N = 14) over the left DLPFC, twice a day for three days with 1–2 days in between. Detailed neuropsychological assessment of five cognitive domains was performed before iTBS and on days 1, 10, and 30 after the last iTBS session. Composite Z-scores were calculated for each domain and for overall cognition. ResultsOur results showed an increase in overall cognition up to one month in both groups but this effect was only significant in the active group. Improvements were seen in the attention domain for both groups and in the visuospatial domain in the active group only. No significant differences were found between the groups. ConclusionThese preliminary findings suggest that active iTBS might improve overall cognitive performance in patients with Parkinson's disease with mild cognitive impairment and that this effect can last up to one month. This cognitive improvement, is likely mediated by improvement on visuospatial abilities. Further studies are needed to explore the potential of iTBS as a therapeutical tool to slow cognitive decline in patients with Parkinson's disease.

P1‐322: APPLICATION OF GROOVED PEGBOARD TEST IN CEREBROSPINAL FLUID TAP TEST OF PATIENTS WITH IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

Motor impairment in NPH can extend beyond gait to include deficits in upper extremity functions and psychomotor speed. The upper extremity function evaluation will be helpful for the NPH patients who are unable to ambulate (e.g. patients is wheelchair bound) may not be able to comply with the gait evaluation. Our study aimed to explore the role of grooved pegboard test in evaluating cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus. The patients with possible idiopathic normal pressure hydrocephalus in the outpatient clinic, the department of neurology, Peking Union Medical College Hospital from 2013 to 2017 were enrolled. All patients underwent detailed neuropsychological and walking assessments, as well as head magnetic resonance imaging. Forty-three patients with iNPH were recruited in the study, excluding patients with severe dementia and those who did not complete the four time points evaluation of CSF tap test for various reasons. The correlation between grooved pegboard test performance and other clinical assessment were analyzed. In DTI analysis of white matter, the FA and MD values of 19 regions of interest were measured by ROI method. The correlation between grooved pegboard test performance and the white matter lesions were also analyzed. There was no significant difference in the results of CSF tap test between positive and negative patients. The results of the grooved pegboard test were significantly correlated with patients' walking ability (10 m walking time, 5 m up-go test time), cognitive function (MMSE, MOCA, Trail Making Test A Z score, digital symbol Z score, STROOP-C Test Z score) and functional score (ADL, iNPHGS total score, iNPHGS walking, iNPHGS cognition) (P < 0.05). The time of left grooved pegboard test was significantly correlated with FA value of right periventricular lesions (P=0.017). The performance of the grooved pegboard test was related to lower extremity motor ability and cognitive function. It can be used as an alternative evaluation tool for patients who are unable to ambulate and may not be able to comply with the gait evaluation. This project was supported by grant from CAMS 2016-12M-1-004, National NSFC81550021, 2016YFC1306300, grant XDPB10.

Prevalence and Risk Factors for Cognitive Impairment and Dementia in Indians: A Multiethnic Perspective from a Singaporean Study.

Dementia is the leading cause of dependency and disability among older persons worldwide. There remains, however, limited studies on dementia rates within the Asia-Pacific region, with little data on differences across major Asian ethnic groups. To study the prevalence of cognitive impairment (CI) and dementia in community-dwelling Indians from Singapore and to examine interethnic differences among Chinese, Malays, and Indians. Participants (>60 years) drawn from the Indian component of the multiethnic Epidemiology of Dementia in Singapore (EDIS) study were screened using the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen-positive participants underwent further detailed neuropsychological assessments. CI was classified into Cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia. Of 961 Indian adults, 120 (12.5%) had CIND-mild, 101 (10.5%) CIND-moderate, and 12 (1.2%) dementia. The overall age-standardized prevalence of any CI was 24.6%. The prevalence of any CI increased with age (15.7% in ages 60-64 years to 30.1% in ages≥80 years), and was higher in women than men. Multivariate analysis showed that age, lower education, and hypertension were independently associated with CI. Even after demographic and cardiovascular risk factor adjustment, Indians were more likely to be cognitively impaired compared to Chinese (odds ratio [OR], 95% CI:1.37 [1.01-1.86]) but not Malays (0.89 [0.72-1.10]). Among elderly Indians, the overall prevalence of any CI was 24.6%. Despite similar assessment protocols and risk factor adjustments, the prevalence of CI was higher in Indians compared to Chinese but similar to Malays. Further research is needed to unravel other factors that may underlie these ethnic differences.

Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study.

Autism spectrum disorder (ASD) is highly prevalent in subjects with Tuberous Sclerosis Complex (TSC), but we are not still able to reliably predict which infants will develop ASD. This study aimed to identify the early clinical markers of ASD and/or developmental delay (DD) in infants with an early diagnosis of TSC. We prospectively evaluated 82 infants with TSC (6–24 months of age), using a detailed neuropsychological assessment (Bayley Scales of Infant Development—BSID, and Autism Diagnostic Observation Schedule—ADOS), in the context of the EPISTOP (Long-term, prospective study evaluating clinical and molecular biomarkers of EPIleptogenesiS in a genetic model of epilepsy—Tuberous SclerOsis ComPlex) project (NCT02098759). Normal cognitive developmental quotient at 12 months excluded subsequent ASD (negative predictive value 100%). The total score of ADOS at 12 months clearly differentiated children with a future diagnosis of ASD from children without (p = 0.012). Atypical socio-communication behaviors (p < 0.001) were more frequently observed than stereotyped/repetitive behaviors in children with ASD at 24 months. The combined use of BSID and ADOS can reliably identify infants with TSC with a higher risk for ASD at age 6–12 months, allowing for clinicians to target the earliest symptoms of abnormal neurodevelopment with tailored intervention strategies.

How Does Circadian Rhythmicity Relate to Neuropsychological and Neuroimaging Markers in Older People at Risk for Dementia?

BACKGROUND: Changes in the circadian regulation of the sleep-wake cycle occur with ageing and may be linked to neurodegeneration. It is unclear the extent to which such changes are evident in mild cognitive impairment (MCI), and how they may relate to neuropsychological functioning, the integrity of key temporal lobe structures and longitudinal decline. METHOD: 334 older individuals (mean age=66.1, sd=8.9) with subjective cognitive impairment (SCI) and MCI (mean MMSE=28.1, sd=1.4) received detailed neuropsychological assessment including Logical Memory, Rey Auditory Verbal Learning Test, Rey Figure and Boston Naming Test. They also received clinical and wrist-worn actigraphic assessment, and a subset of 60 individuals underwent neuroimaging. Circadian rhythm analysis was performed using non-parametric methods to obtain intradaily variability, interdaily stability, and activity during the least and most active 5-hours and 10-hours of the day, respectively. Cosinor methods were also used to derive amplitude, mean, and variability of the rest-activity rhythm. For the neuroimaging subset, cortical thickness of the entorhinal cortex and hippocampal volume were derived using Freesurfer. A subset of 90 individuals had 2-year longitudinal follow-up data from which memory decline scores were computed. RESULTS: Compared to SCI, after controlling for age, participants with MCI showed significantly greater intradaily variability as well as lower amplitude of activity across the circadian period, and lower activity during the most active 10-hour period. Across both groups, circadian disruption was associated with poorer performance on tests of verbal memory (p<0.05), visuospatial memory (p<0.001) and confrontation naming (p<0.001). Lower activity amplitude was associated with reduced cortical thickness in the entorhinal cortex. For those with follow-up data, greater activity during the least active 5-hours of the day was associated with memory decline longitudinally (p<0.05). CONCLUSION: Disruptions to the rest-activity cycle relate to both memory and language decline cross-sectionally and memory decline longitudinally as well as to degeneration of key temporal brain regions. Alterations in this cycle may represent a preclinical or prognostic marker for dementia and may warrant intervention.

D-KEFS ST Failure Identifies Multiple Sclerosis Patients With Worse Objective and Self-Perceived Physical and Cognitive Disability.

Background and Objectives: The Brief Repeatable Battery of Neuropsychological Test (BRB-NT) does not explore the executive functions. We combined BRB-NT and Delis-Kaplan Executive Function System Sorting Test (D-KEFS ST) to obtain a more comprehensive evaluation of cognitive impairment in Multiple Sclerosis (MS) patients.Methods: 137 Relapsing Remitting MS (RRMS) patients underwent a detailed neuropsychological assessment including BRB-NT, D-KEFS ST and self-administrated questionnaires, namely the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), the Fatigue Severity Scale (FSS) and the Beck Depression Inventory-Second Edition (BDI-II).Results: Fifty-four patients (39.4%) had normal scores in each item of both batteries (cognitive normal), while 64 patients (46.7%) failed in at least one test of BRB-NT but not of D-KEFS ST (BRB-NT impaired) and 18 (13.1%) failed in at least one test of both batteries (BRB-NT+D-KEFS ST impaired). Only one patient (0.7%) failed in D-KEFS ST, but not in BRB-NT and was excluded from further analysis. BRB-NT+D-KEFS ST impaired patients had a significant higher mean disease duration and median EDSS score (15.5 ± 13.6 years and 3.5, respectively) compared to those with only BRB-NT impaired (7.9 ± 9.2, p < 0.01 and 2.5, p < 0.05) and with cognitive normal patients (6.7 ± 9.4, p < 0.005 and 2.0, p < 0.01). SDMT was more frequently impaired in BRB-NT+D-KEFS ST impaired patients (77.8%) compared to only BRB-NT impaired ones (20.0%, p < 0.001). The failure in D-KEFS ST was associated with the number of failed BRB-NT items (OR 1.46, IC95% 1.07–1.99, p < 0.05) and with pathological SDMT z-value (OR 10.56, IC95% 2.50–44.66, p < 0.005). Compared to BRB-NT impaired patients and the cognitive normal ones, BRB-NT+D-KEFS ST impaired patients had significant higher MSNQ (p < 0.01) and BDI-II (p < 0.05) values.Conclusion: D-KEFS ST did not increase the number of cognitively impaired MS patients identified by BRB-NT, but provided a more comprehensive evaluation of cognitive decline. D-KEFS ST identified a subgroup of patients with increased self-perception of cognitive decline, depression and higher physical disability.

Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease.

ObjectivesIn this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures.Method127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimodal MRI were performed. SVD scores were calculated on a standard scale, and structural brain network measures were analyzed by diffusion tensor imaging (DTI). Between-group differences were analyzed, and logistic regression was applied to determine the predictive value of SVD and network measures for cognitive status. Mediation analysis with structural equation modeling (SEM) was used to better understand the interactions of SVD burden, brain networks and cognitive deficits.ResultsGroup difference was found on all global brain network measures. After adjustment for age, gender, education and depression, significant correlations were found between global brain network measures and diverse neuropsychological tests, including TMT-B (r = −0.209, p < .05), DSST (r = 0.206, p < .05), AVLT short term free recall (r = 0.233, p < .05), AVLT long term free recall (r = 0.264, p < .05) and Rey-O copy (r = 0.272, p < .05). SVD score showed no group difference and was not correlated with cognition tests. Network global efficiency (EGlobal) was significantly related to cognitive state (p < .01) but not the SVD score. Mediation analysis showed that the standardized total effect (p = .013) and the standardized indirect effect (p = .016) of SVD score on cognition was significant, but the direct effect was not.ConclusionsBrain network measures, but not the SVD score, are significantly correlated with cognition in post-stroke SVD patients. Mediation analysis showed that the cerebral vascular lesions produce cognitive dysfunction by interfering with the structural brain network in SVD patients. The brain network measures may be regarded as direct and independent surrogate markers of cognitive impairment in SVD.

Advances in Understanding, Diagnosis, and Treatment of Tinnitus.

Tinnitus is one of the most common hearing disorders, with wide-ranging risk factors including age, hearing loss, noise exposure, inflammatory diseases or tumors of the ear, ototoxic drugs, head or cervical vertebra trauma, and psychological disorders (e.g., anxiety and depression). Tinnitus can be a lifelong disorder and will bring about annoyance, anxiety, depression, insomnia, hyperacusis, concentration difficulty, and, in some extreme cases, suicide. Not every tinnitus patient will require medical attention, and the majority often get accustomed to the phantom sound; however, about 20% of the sufferers will seek clinical intervention. As a matter of fact, evidence was rare for successful tinnitus treatment with a randomized clinical trial. With recent advances in neuroimaging approaches and development of novel tinnitus animal models, scientists have gained new insights into the neural basis of tinnitus. Current theories regarding mechanisms underlying tinnitus focus on abnormal activities in the central nervous system, such as elevated spontaneous neuronal firing rate and increased neuronal synchronization caused by the auditory deprivation, changes in the tonotopic map, auditory cortical reorganization, dysregulation of the limbic system, and the central auditory cortex. At the present, there is a lack of objective indicator of tinnitus, and the diagnosis battery for tinnitus mainly relies on subjective assessments and self-reports, such as case history, audiometric tests, detailed tinnitus inquiry, tinnitus matching, and neuropsychological assessment. While there is currently no golden standard treatment for tinnitus, counseling, psychotherapy, pharmacological approaches, masking devices, individualized sound stimulation, and cognitive behavioral therapy (CBT) are the most widely used strategies, and among these only CBT treatment has been shown to have a definite improvement effect on tinnitus in a large randomized controlled trial. In summary, this article reviews recent advances in understanding, diagnosis, and treatment of tinnitus.

The applause sign in frontotemporal lobar degeneration and related conditions

The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Recent research, however, has provided evidence for the occurrence of the applause sign in various conditions. The aim of this study was to determine the prevalence of the applause sign and correlate its presence with neuropsychological and MRI volumetry findings in frontotemporal lobar degeneration and related conditions. The applause sign was elicited with the three clap test (TCT), with a higher score indicating poorer performance. Data were recorded from 272 patients from the cohort of the German consortium for frontotemporal lobar degeneration (FTLDc): 111 with behavioral variant frontotemporal dementia (bvFTD), 98 with primary progressive aphasia (PPA), 30 with progressive supranuclear palsy Richardson's syndrome, 17 with corticobasal syndrome (CBS) and 16 with amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). For comparison, 29 healthy elderly control subjects (HC) were enrolled in the study. All subjects underwent detailed language and neuropsychological assessment. In a subset of 156 subjects, atlas-based volumetry was performed. The applause sign occurred in all patient groups (40% in PSP, 29.5% in CBS, 25% in ALS/FTD, 13.3% in PPA and 9.0% in bvFTD) but not in healthy controls. The prevalence was highest in PSP patients. It was significantly more common in PSP as compared to bvFTD, PPA and HC. The comparison between the other groups failed to show a significant difference regarding the occurrence of the applause sign. The applause sign was highly correlated to a number of neuropsychological findings, especially to measures of executive, visuospatial, and language function as well as measures of disease severity. TCT scores showed an inverse correlation with the volume of the ventral diencephalon and the pallidum. Furthermore the volume of the ventral diencephalon and pallidum were significantly smaller in patients displaying the applause sign. Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds PPA and ALS/FTD to these conditions. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation with various cognitive measures we suggest the applause sign to be indicative of disease severity. Furthermore we suggest that the applause sign represents dysfunction of the pallidum and the subthalamic nucleus, structures which are known to play important roles in response inhibition.

Identification of Mild Cognitive Impairment From Speech in Swedish Using Deep Sequential Neural Networks.

While people with mild cognitive impairment (MCI) portray noticeably incipient memory difficulty in remembering events and situations along with problems in decision making, planning, and finding their way in familiar environments, detailed neuropsychological assessments also indicate deficits in language performance. To this day, there is no cure for dementia but early-stage treatment can delay the progression of MCI; thus, the development of valid tools for identifying early cognitive changes is of great importance. In this study, we provide an automated machine learning method, using Deep Neural Network Architectures, that aims to identify MCI. Speech materials were obtained using a reading task during evaluation sessions, as part of the Gothenburg MCI research study. Measures of vowel duration, vowel formants (F1 to F5), and fundamental frequency were calculated from speech signals. To learn the acoustic characteristics associated with MCI vs. healthy controls, we have trained and evaluated ten Deep Neural Network Architectures and measured how accurately they can diagnose participants that are unknown to the model. We evaluated the models using two evaluation tasks: a 5-fold crossvalidation and by splitting the data into 90% training and 10% evaluation set. The findings suggest first, that the acoustic features provide significant information for the identification of MCI; second, the best Deep Neural Network Architectures can classify MCI and healthy controls with high classification accuracy (M = 83%); and third, the model has the potential to offer higher accuracy than 84% if trained with more data (cf., SD≈15%). The Deep Neural Network Architecture proposed here constitutes a method that contributes to the early diagnosis of cognitive decline, quantify the progression of the condition, and enable suitable therapeutics.

Haemoglobin, magnetic resonance imaging markers and cognition: a subsample of population-based study

BackgroundLow haemoglobin is highly prevalent among the elderly and has been associated with dementia. However, the mechanisms underlying this association with cognitive dysfunction, either through cerebrovascular disease or neurodegeneration, remain poorly understood. We aimed to examine the association of decreased haemoglobin levels with markers of cerebral small vessel disease (CSVD), neurodegeneration and cognitive impairment in an elderly Asian population.MethodsA total of 796 Chinese, Malay and Indian participants aged 60 years and older from the Epidemiology of Dementia in Singapore study were included in this study. After providing information on demographics, anthropometry and cardiovascular risk factors, participants underwent 3-T brain magnetic resonance imaging (MRI) to measure markers of CSVD, including cerebral microbleeds, cortical cerebral microinfarcts, lacunes, enlarged perivascular spaces and white matter hyperintensities, as well as neurodegenerative markers, including cortical thickness and subcortical structure volumes quantified using FreeSurfer. Cognition was assessed using a detailed neuropsychological assessment. Logistic and linear regression models were constructed, adjusting for age, gender, education, race, body mass index, smoking, hypertension, hyperlipidaemia, diabetes, glomerular filtration rate and other MRI markers, to test the association between haemoglobin levels and the MRI markers and cognition.ResultsDecreased haemoglobin levels were associated with cerebral microbleeds, specifically lobar microbleeds (OR, 1.21; 95% CI, 1.04–1.40; p = 0.015). Decreased haemoglobin levels were also associated with occipital cortical thinning (mean difference, − 0.011; 95% CI, − 0.019, − 0.004; p = 0.003) and smaller accumbens volume (mean difference, − 0.01; 95% CI, − 0.02, 0.00; p = 0.005). A significant association was also observed between decreased haemoglobin levels and poorer global cognitive performance (mean difference, − 0.04; 95% CI, − 0.09, 0.00; p = 0.048). In cognitive domain analysis, associations were again observed between decreased haemoglobin levels and worse performance on attention (mean difference, − 0.05; 95% CI, − 0.10, − 0.01; p = 0.028) and language (mean difference, − 0.06; 95% CI, − 0.12, 0.00; p = 0.048) domains; however, these associations did not survive multiple comparison.ConclusionsDecreased haemoglobin levels were associated with lobar microbleeds, neurodegenerative markers and cognitive dysfunction. Future studies should ascertain whether iron, folate or vitamin B12 supplementation is able to ameliorate the onset and progression of cognitive impairment and dementia associated with low haemoglobin.

Study protocol: Care of Late-Stage Parkinsonism (CLaSP): a longitudinal cohort study

BackgroundParkinson’s disease (PD) is a chronic progressive disorder leading to increasing disability. While the symptoms and needs of patients in the early stages of their disease are well characterized, little information is available on patients in the late stage of the disease.Methods/designThe Care of Late-Stage Parkinsonism (CLaSP) study is a longitudinal, multicenter, prospective cohort study to assess the needs and provision of care for patients with late stage Parkinsonism and their carers in six European countries (UK, France, Germany, Netherlands, Portugal, Sweden). In addition, it will compare the effectiveness of different health and social care systems. Patients with Parkinsonism with Hoehn and Yahr stage ≥IV in the “On”-state or Schwab and England stage 50% or less are evaluated at baseline and three follow-up time-points. Standardised questionnaires and tests are applied for detailed clinical, neuropsychological, behavioural and health-economic assessments. A qualitative study explores the health care needs and experiences of patients and carers, and an interventional sub-study evaluates the impact of specialist recommendations on their outcomes.DiscussionThrough the combined assessment of a range of quantitative measures and qualitative assessments of patients with late stage parkinsonism, this study will provide for the first time comprehensive and in-depth information on the clinical presentation, needs and health care provision in this population in Europe, and lay the foundation for improved outcomes in these patients.Trial registrationThe protocol was registered at ClinicalTrials.gov as NCT02333175 on 07/01/2015.