Ting Ting Yong

Progression of small vessel disease correlates with cortical thinning in Parkinson’s disease

OBJECTIVE Cerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinsons disease (PD), however the pathophysiological role of SVD in PD-dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition. METHODS Seventy-three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no-progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance. RESULTS Fourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months. DISCUSSION The extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD.

Interaction between APOE-ɛ4 and HMGB1 is associated with widespread cortical thinning in mild cognitive impairment

Biomarkers which allow for identification of the underlying aetiology of mild cognitive impairment (MCI) are of prognostic importance. In addition to the amyloid-β and hyperphosphorylated tau pathology, genetic factors such as apolipoprotein E (APOE)-e4 and neuroinflammation may have additional roles in the pathogenesis of Alzheimer’s Disease (AD). In this study, we investigated the influence of APOE-ɛ4 status, neuroinflammation as measured by high mobility group box 1 protein (HMGB1), and their interaction effect on cortical thickness in MCI. We hypothesised that the interaction between APOE-ɛ4 and HMGB1 would result in a more widespread pattern of cortical thinning compared with either one factor alone. Fifty-two individuals (27 mild cognitive impairment (MCI) and 25 controls) were recruited from a tertiary neurological centre. MCI was clinically diagnosed using the National Institute on Aging and the Alzheimer’s Association workgroup (NIA-AA) criteria.1 They had a Clinical Dementia Rating (CDR) score of 0.5 and had no other disease that could account for their cognitive deficits. Subjects with active systemic inflammatory states including infections, recent surgery or acute strokes and those receiving anti-inflammatory or cancer treatment were excluded as they could affect the levels of high mobility group box 1 protein (HMGB1). This study was approved by the SingHealth Institutional Ethics Review Board and written informed consent was obtained for all. Blood samples were collected from all subjects. Genomic DNA was extracted from peripheral blood with QIAamp DNA Blood Maxi Kit (Qiagen, Hilden, Germany). Genotyping for apolipoprotein E (APOE) was performed as described previously.2 Subjects with at least a single copy of …

MILD COGNITIVE IMPAIRMENT ASSOCIATED WITH PARKINSON’S DISEASE (PD-MCI) AND MCI ASSOCIATED WITH ALZHEIMER’S DISEASE (AD-MCI) HAVE DISTINCT COGNITIVE PROFILES: A LONGITUDINAL STUDY

many significantly different features both under singleand dual-task walking scenarios. However, dual–task scenario provides better discrimination between MCI and HC subjects. The MCI people presented significantly higher swing time, stance time, stride time, CVof swing time, CVof stride time while having lower cadence and gait speed in comparison with the HCs. Conclusions:The inertial sensor based pervasive gait analysis method provides many assistive markers or indicators to help MCI diagnosis and facilitates the early detection of AD.

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.

DEVELOPMENT AND VALIDATION OF THE SQOL INSTRUMENT TO MEASURE QOL IN MILD DEMENTIA

Tobeconcrete, these estimates canbeusedas adjustment factorsand itmeans subtracting 6.78 to form B, adding 1.14 to form C, and subtracting 6.33 from formD immediate memory index score 60 69 scores. To be concrete, it means adding 3.6 to form B, adding 4.86 to form C, and adding 0.55 from form D visuospatial constructional index score6069 scores.Tobeconcrete, itmeans adding 5.57 to form B, adding 9.7 to form C, and subtracting 2.14 from form D language index score 60 69 scores. This adjustment is after the systematic correction of the semantic fluency form correction suggested by Randolph for theEnglish form language index score 60 69 scores.Tobe concrete, itmeans adding 0.93 to formB, adding 0.64 to formC, and subtracting 1.38 from formD attention index score 60 69 scores. To be concrete, it means subtracting 3.65 to form B, subtracting 0.76 to form C, and subtracting 2.43 from form D delayed memory index score 60 69 scores. The total index scorewas calculated by summing the 5 transformed subscale scores for French-testing participants and obtaining their new total index score from lookup tables. Poster Presentations: Sunday, July 22, 2018 P561

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

FEASIBILITY OF VIRTUAL REALITY IN COGNITIVE ENHANCEMENT FOR PERSONS WITH YOUNG ONSET COGNITIVE IMPAIRMENT: A PRELIMINARY STUDY

Background: Atypical antipsychotics have been highlighted in clinical practice due to ability to promote antipsychotic action at recommended doses without producing extrapyramidal symptoms and better efficacy for positive, negative and cognitive symptoms. Methods: A quantitative and qualitative research was undertaken with 20 neurologists (NEU) and 10 geriatricians (GER) to explore their prescriptive routine over aripiprazole, olanzapine, risperidone and quetiapine, as well as to evaluate indications versus patient profiles for these drugs. Results: The major diseases for which physicians prescribe atypical antipsychotics are: Dementia (35%: NEU; 70%: GER), Alzheimer’s (45%: NEU), Insomnia / sleep disorder (30%; NEU), Depression (70%: GER) and Schizophrenia (40%: GER). With respect to the most appropriate patient profile for each drug: between neurologists and geriatricians, aripiprazole is suitable for: patients with higher purchasing power, who did not respond to previous treatment, treatment of negative symptoms / blunting, mania / hypomania crisis and young patients. Olanzapine is suitable for: patient with normal / lean weight, higher purchasing power, younger, negative symptoms / blunting, failure of previous treatment, with insomnia or sleep disorders. Quetiapine is suitable for: elderly patient, with insomnia / sleep disorders, mild or moderate clinical condition, failure of previous treatment, acute phase of illness and with associated anxiety. In turn, risperidone is suitable for: failure of previous treatment, patient with normal / lean weight, first psychotic episode, elderly patient and with mild or moderate clinical condition. The most commonly prescribed antipsychotics are quetiapine and risperidone and the main reasons are given in Table 1. Conclusions: Physicians use several options of antipsychotics in clinical practice, adapting the treatment to patient profile. The results showed that prescription took in account multiple presentations, easy dosage adjustment, safety related to extrapyramidal effects, action on insomnia and symptoms of agitation and aggressiveness, efficacy in psychotic episodes and dementia.

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.

DIFFERENTIATING FRONTAL VARIANT ALZHEIMER'S DISEASE FROM BEHAVIOURAL VARIANT FRONTOTEMPORAL DEMENTIA

prepare sites and investigators for FTLD clinical trials. Clinical, biomarker, genetic and imaging data from ARTFL and LEFFTDS will soon be available to investigators worldwide. Kipp Right frontal, mean (s) 2.2 (1.1) 2.2 (1.1) 0.98 Kipp Left frontal, mean (s) 2.3 (0.9) 2.0 (0.7) 0.56 Kipp Right anterior temporal, mean (s) 1.6 (1.2) 2.0 (0.7) 0.55 Kipp Left anterior temporal, mean (s) 1.9 (0.9) 2.0 (0.7) 0.85 Kipp Right posterior temporal, mean (s) 1.6 (0.7) 2.0 (0.7) 0.24 P2-304 DIFFERENTIATING FRONTALVARIANT