Levinia Lim

Depressive symptoms influence global cognitive impairment indirectly by reducing memory and executive function in patients with mild cognitive impairment

Background Depressive symptoms negatively influence global cognition in the elderly; however, the mechanism of this effect remains unclear. Objective To investigate whether depressive symptoms influence global cognitive function in patients with mild cognitive impairment (MCI) and mild Alzheimers disease (AD) by impeding specific neuropsychological abilities and under what conditions this effect might occur. Method A sample of 259 participants (104 cognitively normal elderly controls, 66 patients with MCI and 89 patients with mild AD) underwent a comprehensive neuropsychological assessment. Global cognitive impairment was indexed by the composite of Mini-Mental State Examination and Montreal Cognitive Assessment scores and severity of depressive symptoms was measured with the Geriatric Depression Scale (GDS). Results Among patients with MCI, greater severity of depressive symptoms was associated with greater global cognitive impairment, with a moderate effect size. A mediation analysis revealed that patients with MCI experiencing depressive symptoms may exhibit global cognitive impairment because their depressive symptoms were reducing their capacity for working memory, episodic memory and non-speed-based executive functions. A moderation analysis indicated that this effect was consistent across age, gender, years of education and APOE-e4 status for working memory and episodic memory, and was observed in patients with MCI older than 65 years for executive functions. In cognitively normal elderly adults and patients with AD, depressive symptoms were not associated with global cognitive impairment. Conclusions Depressive symptoms influence global cognitive function in patients with MCI indirectly by reducing mental space, mental flexibility and their capacity for consolidating and retrieving memories. These findings may guide clinicians to better diagnose and manage cognitive impairment in the context of concomitant depressive symptoms.

Getting Lost Behavior in Patients with Mild Alzheimer’s Disease: A Cognitive and Anatomical Model

Background Getting lost behavior (GLB) in the elderly is believed to involve poor top-down modulation of visuospatial processing, by impaired executive functions. However, since healthy elderly and elderly with Alzheimer’s disease (AD) experience a different pattern of cognitive decline, it remains unclear whether this hypothesis can explain GLB in dementia. Objective We sought to identify whether poor executive functions and working memory modulate the relationship between visuospatial processing and prevalence of GLB in healthy elderly and patients with AD. Complementary to this, we explored whether brain regions critical for executive functions modulate the relationship between GLB and brain regions critical for visuospatial processing. Method Ninety-two participants with mild AD and 46 healthy age-matched controls underwent neuropsychological assessment and a structural MRI. GLB was assessed using a semistructured clinical interview. Path analysis was used to explore interactions between visuospatial deficits, executive dysfunction/working memory, and prevalence of GLB, in AD and controls independently. Results For both healthy controls and patients with mild AD, visuospatial processing deficits were associated with GLB only in the presence of poor working memory. Anatomically, GLB was associated with medial temporal atrophy in patients with mild AD, which was not strengthened by low frontal gray matter (GM) volume as predicted. Instead, medial temporal atrophy was more strongly related to GLB in patients with high frontal GM volumes. For controls, GLB was not associated with occipital, parietal, medial temporal, or frontal GM volume. Conclusion Cognitively, a top-down modulation deficit may drive GLB in both healthy elderly and patients with mild AD. This modulation effect may be localized in the medial temporal lobe for patients with mild AD. Thus, anatomical substrates of GLB in mild AD may not follow the typical top-down modulation mechanisms often reported in the healthy aging population. Implications advance therapeutic practices by highlighting the need to target both working memory and visuospatial deficits simultaneously, and that anatomical substrates of GLB may be disease specific.

The influence of language and culture on cognitive assessment tools in the diagnosis of early cognitive impairment and dementia

ABSTRACT Introduction: Cognitive assessment tools measure cognitive impairment and complement biomarkers to link cognitive symptoms with pathophysiological processes underlying dementia. However, language and cultural differences in multilingual populations can influence the interpretation of cognitive assessment tools when applied in cross-cultural and multinational studies. Areas covered: This article examines the influence of culture and language on the interpretation of the Mini-Mental State Examination, Montreal Cognitive Assessment, and Alzheimer’s Disease Assessment Scale-cognitive subscale, which are more commonly used worldwide. It discusses how this impacted multinational studies. Lastly, it presents language-neutral tools such as the Visual Cognitive Assessment Test, which do not require translation when applied in multilingual populations. Expert commentary: Linguistic and cultural variation within tools due to translation and differences in administration introduce method bias and differential item functioning, which influence the interpretation of cognitive scores in multinational studies. The ultimate goal is to have a tool that accurately measures cognitive impairment, yet with minimal influence from linguistic, cultural, educational, and demographic differences, through concerted international efforts to harmonize the development and validation of tools. While recently developed visual-based language-neutral tools show promise in the early detection of cognitive impairment, further validation will be required for these tools to be applied internationally.

EVALUATION OF COGNITIVE ENHANCEMENT AND COGNITIVE STIMULATION PROGRAMMES FOR ASIAN PATIENTS WITH MILD COGNITIVE IMPAIRMENT OR MILD DEMENTIA

and related dementias. NPS are particularly problematic during hospitalization, placing patients at increased risk for a range of adverse and costly outcomes. Despite clear guidelines recommending non-pharmacologic approaches as first-line therapy for NPS, these are under-utilized in the hospital setting. This gap is exacerbated by a lack of feasible hospital-based interventions to help clinicians determine and address the underlying causes of NPS. Our aim was to develop, implement and evaluate the PeRsOnalized ApproaCh and Targeted InterVEntions (PROACTIVE) Treatment Protocol, a multi-component decision support protocol and intervention designed to address the specific work-process and system challenges of acute care with the goals of improving use of evidence-based treatment responses and reducing stress/burden among staff. Methods:Work system mapping techniques were employed to design a detailed, systematic treatment protocol including documentation templates, physical environment reminders and built-in intervention resources. We conducted a matched-sample pre-post implementation study to determine the feasibility/acceptability of PROACTIVE and obtain preliminary estimates of its impact on use of non-pharmacologic treatment responses, staff confidence and stress/burden. Patient characteristics and treatment responses were abstracted from the medical record for all eligible dementia patients during the 6 months prior to the pilot intervention launch and for patients enrolled in the 6-month pilot. Results:The PROACTIVE Treatment Protocol incorporates four integrated care processes: individualized needs assessment, prevention strategies, systematic pain assessment/treatment algorithm and symptom-specific treatment guidance. Over a 6-month period, 28 patients were enrolled in the treatment protocol. Nursing staff delivered 47 non-pharmacologic symptom-specific treatment responses, 67% of which were deemed effective on first treatment cycles. Nursing teams reported feeling more supported and comfortable in responding to NPS. Key implementation challenges include the need for ongoing staff training, feedback on progress and changes in staffing.Conclusions:PROACTIVEwas successfully designed and piloted by a research and clinical team, and has been effective in increasing comfort in AD symptom management. Future steps include ongoing implementation and evaluation of patient-level metrics.

THE ROLE OF COMPREHENSIVE INVESTIGATION IN THE DIAGNOSTIC WORK-UP OF YOUNGER PATIENTS WITH COGNITIVE IMPAIRMENT

and adjusted for age. WM tracks that significantly correlated with EYO were further evaluated with pathological biomarkers (cerebrospinal fluid (CSF) amyloid and tau). Results:Significant changes in mean diffusivity and radial diffusivity were seen within parietal and frontal regions for MC CDR>0 compared to other groups (Fig1). Within the MC group, three WM tracks were significantly associated with EYO: forceps major (FMaj), cingulum, and posterior corpus callosum (PCC). Initial decline in WM for MC and NC occur around 10 years prior to EYO. A significant interaction was observed for mutation status and EYO in the cingulum. CSF amyloid correlated with average mean fractional anisotropy (FA; p1⁄40.02) but not with any specific WM track. CSF T-tau correlated with FA for the PCC (p1⁄40.04) and FMaj (p1⁄40.001). Conclusions: This data reveals that WM integrity in ADAD is most strongly affected in posterior/parietal white matter with more advanced disease. These changes suggest that structural decline may initiate just before EYO that associates with the underlying pathology.

ELUCIDATING THE RELATIONSHIP BETWEEN NEUROPSYCHIATRIC SYMPTOMS AND COGNITIVE SUBSTRATES IN MILD ALZHEIMER’S DEMENTIA

Background: Neuropsychiatric symptoms are common among persons with dementia and have been associated with poorer cognitive outcomes. A study, for example, found that behavioral changes significantly correlated with frontal dysfunction. To date, it remains unclear how the neuropsychiatric symptoms are uniquely associated with different domains of cognitive impairments. To investigate the association between cognitive domains and neuropsychiatric symptoms in mild Alzheimer’s Disease (AD). Methods:A cohort of patients diagnosed with mild AD based on the NIA-AA critera was recruited from a tertiary neurology centre (n 1⁄4 177). Each patient went through an extensive battery of neuropsychological assessments, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was administered and completed by their caregiver. Factor analyses were conducted to cluster NPI-Q and cognitive test scores into clusters of neuropsychiatry and cognitive domains respectively. Stuctural equation modelling was used to delineate significant associations between the neuropsychiatric clusters and the various cognitive domains. Results: NPI-Q scores were clustered into three subsyndromes—mood, behavior, and psychosis. Scores from the neuropsychological assessments were also clustered into five primary cognitive domains—memory, visuospatial, attention, executive function, and language. The Behavioral cluster was significantly related to every cognitive domain, with Attention being the primary predictor (b 1⁄4 -0.13, p 1⁄4 0.002). In contrast, the Mood cluster was shown to only have a significant relationship with Language (b 1⁄4 -0.24, p 1⁄4 0.001). Finally, significant associations were found between Psychosis and Language (b 1⁄4 -0.03, p 1⁄4 0.002), as well as Psychosis and Executive Function (b 1⁄4 -0.06, p 1⁄4 0.002) (Figure 1). Conclusions:Neuropsychiatric symptoms among patients with mild Alzheimer’s are shown to be associated with impairments in specific cognitive domains. For greater efficacy, clinical interventions addressing behavioral concerns should consider strategies that target the underlying cognitive substrate. P2-302 CLINICAL FEATURES AND DIAGNOSIS OF EARLY ONSET DEGENERATIVE DEMENTIAS IN TURKEY Başar Bilgiç, Bedia Samancı, Zeynep Tufekcioglu, Asli Demirtas Tatlidede, Erdinc Dursun, Duygu Gezen-Ak, Hasmet A. Hanagasi, Hakan I. Gurvit, Murat Emre, Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; Brain and Neurodegenerative Disorders Research Unit, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Contact e-mail: bilgicb@gmail.com

MEDIAL TEMPORAL ATROPHY IN AMYLOID-NEGATIVE, YOUNG-ONSET DEMENTIA IS ASSOCIATED WITH HIGH WHITE MATTER HYPERINTENSITY

AV1451 change based on PiB status in OA. Mixed effects models showed significant differences in AV1451 change over time between AD and OA in Braak III/IV (mean AD AV1451-APC1⁄44.38%, p<0.05; Fig.2) and Braak V/VI (AD AV1451-APC1⁄45.14%, p<0.05), but not Braak I/II (AD AV1451-APC1⁄4-0.66%, p>0.3). Voxelwise analyses of AV1451 change in AD showed significant increases in lateral and medial frontal lobes (p<0.001, uncorrected; Fig.3A), while atrophy over the same interval was more widespread (Fig.3B). In OA, AV1451 binding significantly increased in bilateral temporal lobe and retrosplenial cortex (p<0.001, cluster FWE p<0.05; Fig.4A). There were no voxelwise differences related to sex, PiB, or APOE. Atrophy in OAwas observed in temporal and parietal lobes with limited frontal involvement (FWE p<0.05; Fig.4B). Conclusions: Our findings provide evidence of in vivo tau accumulation in OA especially in regions associated with early tau deposition. Tau accumulation in OA occurs mostly in regions where cortex is thinning (Fig.5). In AD, tau accumulation is more severe across the brain and group-level increases are in regions associated with ‘later’ tau pathology.

CONSTRUCT VALIDITY OF THE VISUAL COGNITIVE ASSESSMENT TEST (VCAT): AN INTERNATIONAL LANGUAGE-NEUTRAL COGNITIVE SCREENING TOOL

**p<.001 b 1⁄4 standardized beta coefficient of multiple linear regression, controlling for Adjusted p-value 1⁄4 Adjusted for gender, age, race, years of education and lang Figure 1. Patterns of scores across neuropsychological domains of Language, Episodic Memory, Working Memory, Executive Function, and Processing Speed, for each of the classes. Note. Class 1 1⁄4 High Risk. Class 2 1⁄4 Low Average/ poorMemory.Memory. Class 31⁄4Average. Class 41⁄4Dysexecutive Function. Class 5 1⁄4 Elite. Language 1⁄4 CAT; letter fluency; Boston Naming Task. Primary Memory 1⁄4 Digit Span. Secondary Memory 1⁄4 Free Recall; Logical Memory. Processing Speed 1⁄4 Trail Making Test A; Digit Symbol Coding. Executive Function 1⁄4 Trail Making Test B; Block Design. Poster Presentations: Tuesday, July 24, 2018 P1299

A novel language-neutral Visual Cognitive Assessment Test (VCAT): validation in four Southeast Asian countries

BackgroundCognitive screeners are imperative for early diagnosis of dementia. The Visual Cognitive Assessment Test (VCAT) is a language-neutral, visual-based test which has proven useful for a multilingual population in a single-center study. However, its performance utility is unknown in a wider and more diverse Southeast Asian cohort.MethodsWe recruited 164 healthy controls (HC) and 120 cognitively impaired (CI) subjects- 47 mild cognitive impairment (MCI) and 73 mild Alzheimer’s disease (AD) dementia participants, from four countries between January 2015 and August 2016 to determine the usefulness of a single version of the VCAT, without translation or adaptation, in a multinational, multilingual population. The VCAT was administered along with established cognitive evaluation.ResultsThe VCAT, without local translation or adaptation, was effective in discriminating between HC and CI subjects (MCI and mild AD dementia). Mean (SD) VCAT scores for HC and CI subjects were 22.48 (3.50) and 14.17 (5.05) respectively. Areas under the curve for Montreal Cognitive Assessment (0.916, 95% CI 0.884–0.948) and the VCAT (0.905, 95% CI 0.870–0.940) in discriminating between HCs and CIs were comparable. The multiple languages used to administer VCAT in four countries did not significantly influence test scores.ConclusionsThe VCAT without the need for language translation or cultural adaptation showed satisfactory discriminative ability and was effective in a multinational, multilingual Southeast Asian population.

Atrial Fibrillation is Independently Associated with Cognitive Impairment after Ischemic Stroke

BACKGROUND While atrial fibrillation (AF) is an important risk factor for ischemic strokes and mild cognitive impairment (MCI) in Alzheimers disease, the association between AF and post-stroke cognitive impairment (PSCI), and the factors mediating this association, is unclear. OBJECTIVE To investigate the role of AF in PSCI, especially in relation to other markers of cerebrovascular disease. METHODS 445 subjects with mild ischemic stroke without pre-stroke cognitive decline were assessed 3-6 months post-stroke for cognitive deficits. MRIs were reviewed by trained raters for acute infarct characteristics, global cortical atrophy, white matter hyperintensities, cerebral microbleeds, and intracranial stenosis. Logistic regression analysis was used to identify factors independently associated with PSCI. Subjects were also categorized according to paroxysmal (pAF) or persistent/chronic AF (p/cAF), and presence or absence of AF or large cortical infarcts (LCI) to study cognitive trends. RESULTS 80 (18.0%) subjects had AF. 76.3% of AF subjects and 42.7% of subjects without AF had PSCI. The odds ratio (OR) of AF in developing PSCI was 2.31 (95% CI: 1.12-4.75; p = 0.035), after correcting for other risk factors. pAF subjects and AF subjects with LCIs had higher ORs for PSCI. AF subjects performed worse in neuropsychological tasks associated with global cognition, episodic memory, and executive function. CONCLUSION AF is a significant risk factor for PSCI, even after correcting for AF-related infarcts. Other mechanisms, such as hypoperfusion, microhemorrhages, and neuroinflammation, may be at play. All stroke patients with AF, regardless of the type of infarction, should be closely monitored for PSCI.