Stanislav Sutovsky

Combined aerobic-strength exercise improves cognitive functions in patients with mild cognitive impairment

important given the trend toward earlier and more accurate diagnosis of dementia and the emphasis on providing person-centered care. SHARE’s approach involves discussions led by a SHARE counselor with both “SHARE partners”. This approach has shown great promise in previous trials for improving a variety of outcomes for both individuals. Moreover, SHARE has been found to be feasible and acceptable to early-stage families: persons who have early-stage dementia are often fully aware of the meaning of their diagnosis and able to communicate care choices and preferences. This presentation will describe the SHARE Program and report on the results of its randomized controlled trial with 130 care dyads (e.g., improved carer symptoms of depression, lessened relationship strain, and increased service use). Discussion will focus on the utility of a dyadic approach, future directions for the SHARE program, and the implications for enhancing the shortand longterm well-being of both care partners.

Aerobic-strength exercise improves metabolism and clinical state in Parkinson's disease patients

Regular exercise ameliorates motor symptoms in Parkinson’s disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (31P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson’s disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT02253732.

Clinical accuracy of the distinction between Alzheimer's disease and frontotemporal lobar degeneration

Alzheimers disease (AD) is the most common cause of dementia. Frontotemporal lobar degeneration (FTLD), although less prevalent overall, is almost as common as AD in patients under the age of 65. AD and FTLD are histopathologically distinct, with AD being characterised by extracellular amyloid plaques and intraneuronal neurofibrillary tangles, and FTLD by the presence of non-AD histological pathology, most commonly either tau-positive inclusions or ubiquitin-positive or TDP 43 positive inclusions. Clinically, AD and FTLD may occur with overlapping symptoms, especially in the early stages of the disease. In the case of Alzheimers disease, it is represented by isolated decline of recent episodic memory; later on, by the impairment of time and space orientation, whereby the alteration of social behaviour and amnesic aphasia occur predominantly in the advanced phases of the disease. Frontotemporal lobar degeneration is demonstrated in three clinical subunits: 1) The behavioural-dysexecutive variant of FTLD (frontotemporal dementia, the frontal variant of FTLD, {fvFTLD}), 2) Progressive non-fluent aphasia, 3) Semantic dementia (SD) with the profound impairment of social conduct (fvFTLD) or with severe speech impairment (PNFA, SD). Considering the different clinical symptomatology with FTLD diagnostics, it is necessary to use different psychometric tests than in the case of Alzheimers disease. Therapy and the degree of dependence of the affected person are also different. All three diseases within the FTLD category, mainly the behavioural-dysexecutive variant, require a higher level of nursing care on the part of other persons or institutions in comparison with Alzheimers disease. The goal of our publication is to point to the differences in clinical manifestation and the findings of auxiliary examinations that are helpful in the clinical accuracy of the distinction between these two types of dementia (Tab. 1, Fig. 3, Ref. 18).

Optical coherence tomography and its use in optical neuritis and multiple sclerosis.

Optical coherence tomography is a relatively new non-invasive imaging technique used for obtaining the images and quantifying the layers of the retina. It also provides information about optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlates with axonal loss. Until now, this method was used mainly in ophthalmology; now it has emerged as relevant in neurology as well. RNFL thickness is of particular interest in optic neuropathies and in multiple sclerosis. In sclerosis multiplex, axonal loss occurs as early as the first stages and the quantification of the RNFL thickness by OCT provides an indirect measure of axonal and neuronal loss in the anterior visual pathways. Because OCT is noninvasive, easy to obtain, and highly reproducible, it can be used as a marker of axonal loss and as an endpoint in clinical trials. This paper presents a comprehensive summary of the use of this new diagnostic method in multiple sclerosis patients (Fig. 1, Ref. 58).

Prevalence, Recognition, and Treatment of Dementia in Assisted Living Facilities

Background/Aims: Dementia and psychiatric disorders are common in assisted living facilities (ALFs) and have suboptimal rates of recognition and treatment. Therefore, we aimed to obtain a direct estimate of the prevalence of cognitive impairment and especially dementia among residents of ALFs in western Slovakia and their rates of primary recognition and adequate treatment. Methods: We conducted two cross-sectional studies. Ten ALFs within the city of Bratislava were chosen for the study in 2004, and again in 2011. A total of 866 residents in ALFs were examined in 2004, and 821 residents in ALFs were examined in 2011. The rate and characterization of dementia, its primary recognition and adequate treatment were investigated in both cross-sectional studies. Results: In 2004, 57% of the participants had dementia. Only 7.2% of the participants with probable Alzheimer disease were treated with acetylcholinesterase inhibitors. In 2011, we observed a significant improvement in primary diagnostics and therapy. 66.9% of the cases of dementia were adequately evaluated, and 52.1% were adequately treated. Conclusion: Cognitive deficit and dementia are significantly underdiagnosed and undertreated in assisted living settings. In the second cross-sectional study we detected significant but not complete improvement in the primary recognition and adequate therapy of dementia.

A LINK BETWEEN COGNITIVE FUNCTION AND PHYSICAL ACTIVITY: THE IMPACT OF AEROBIC-STRENGTH EXERCISE IN SENIORS WITH MILD COGNITIVE IMPAIRMENT AND/OR IMPAIRED GLUCOSE METABOLISM

was similar between the experimental (n1⁄430, 68%), and control conditions (n1⁄427, 67.5%), but participants in the experimental condition were more likely to return for subsequent evaluations (T11⁄4100%, T21⁄493%) than participants in the control condition (T11⁄480%, T21⁄472%). Across training conditions, global cognition improved following the intervention, t(74)1⁄44.7, p<0.001, with improvements maintained at follow-up, t(73)1⁄43.9, p<0.001. Conclusions:Tailored and adaptive, as well as more generic CCT improved overall cognitive function in older diabetic adults, both in the short term and in the long-term. This suggests that in T2D elderly, cognitive activity in general may have long-term benefits for cognition. The lack of effect on disease management is consistent with prior investigations where no transfer of skills to other domains have been found. Evaluation of secondary outcomes, including specific cognitive domains and self-efficacy, is underway.

NEUROPATHOLOGY OF EARLY-ONSET FAMILIAL ALZHEIMER'S DISEASE CAUSED BY PRESENILIN-1 MISSENSE MUTATION THR116ASN

Background: Individuals with primary age-related tauopathy (PART) have neurofibrillary tangles in regions comparable to early/moderatestage Alzheimer’s disease (AD), absent of amyloid plaques. Few studies have investigated the clinical diagnoses among individuals with PART. We aimed to: 1) describe the primary and contributing diagnoses in individuals with PART; 2) compare clinical diagnoses in thosewith PART versus AD neuropathology (ADNP); and 3) examine if individualswithPARTless frequently receive aclinicalADdiagnosis than those with ADNP. Methods:We used data on 1,354 participants from the National Alzheimer’s Coordinating Center’s Uniform Data Set (UDS) and Neuropathology Data Set, restricting to those with no neuritic plaques (i.e., PART) or moderate/frequent neuritic plaques (i.e., ADNP); aUDSvisit within two years of autopsy; nomajor co-pathologies; and mild cognitive impairment (MCI) or dementia at last visit. Analyses were stratified by cognitive status at last visit (MCI or dementia). To assess if PART participants were significantly less likely to receive aprimaryor contributing clinical diagnosis ofADat their last visit, we used multivariable logistic regression, controlling for age at death, sex, education, and presence of 1 apolipoprotein e4 allele. Results: The PART sample included 49 individuals with MCI and 112 with dementia, and the ADNP sample included 75 with MCI and 1,118 with dementia. Primary clinical diagnoses of AD were more common in those with ADNP (MCI: 69%, demented: 86%) than PART (MCI: 57%; demented: 52%). Among demented participants, primary clinical diagnoses of PPA/bvFTD or vascular brain injury/ vascular dementia were more common in those with PART than ADNP. Contributing clinical diagnoses of depression were more common in thosewith PART thanADNP. In the adjusted analysis, primary/ contributing clinical diagnoses of AD remained less likely in PART versus ADNP participants with dementia (odds ratio: 0.22, 95% confidence interval: 0.13-0.38). Conclusions: Although there are no accepted in vivo diagnostic criteria for PART, this study suggests that clinicians may recognize the distinction between PART and ADNP when making clinical diagnoses, diagnosing AD less frequently in those with PART. Nonetheless, clinical AD was diagnosed 50% of the time in PART participants with MCI or dementia. P1-500 NEUROPATHOLOGY OF EARLY-ONSET FAMILIAL ALZHEIMER’S DISEASE CAUSED BY PRESENILIN-1 MISSENSE MUTATION THR116ASN Stanislav Sutovsky, Peter Turcani, Petr Novak, Norbert Zilka, Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia; AXON Neuroscience CRM Services SE, Bratislava, Slovakia; AXON Neuroscience R&D, Bratislava, Slovakia. Contact e-mail: nilusuto@gmail.com

EFFECTS OF ENDURANCE-STRENGTH TRAINING ON MOTOR FUNCTIONS, COGNITION AND GLUCOSE METABOLISM IN PATIENTS WITH PARKINSON'S DISEASE

P2-021 EFFECTS OF ENDURANCE-STRENGTH TRAINING ON MOTOR FUNCTIONS, COGNITION AND GLUCOSE METABOLISM IN PATIENTS WITH PARKINSON’S DISEASE Jozef Ukropec, Patrik Krumpolec, Lucia Slobodova, Veronika Tirpakova, Matej Vajda, Eva Heckova, Rouyun Ma, Radka Klepochova, Igor Straka, Silvia Vallova, Stanislav Sutovsky, Zuzana Kosutzka, Chia-Liang Tsai, Ming-Chyi Pai, Peter Turcani, Ulrike Dydak, Wolfgang Bogner, Martin Krssak, Peter Valkovic, Milan Sedliak, Barbara Ukropcova, Institute of Experimental Endocrinology Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Experimental Endocrinology, Biomedical Research Center, SAS, Bratislava, Slovakia; Faculty of Medicine, Comenius University, Bratislava, Slovakia; Slovak Medical University, Institute of Sports Medicine, Bratislava, Slovakia; Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia; Internal Medicine III, Medical University of Vienna, Vienna, Austria; School of Health Sciences, Purdue University, West Lafayette, IN, USA; Medical University Vienna, Vienna, Austria; Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia; Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan; National Cheng Kung University Hospital, Tainan, Taiwan; School of Health Sciences, Purdue University, West Lafayette, IN, USA; Medical University of Vienna, Vienna, Austria; Institute of Experimental Endocrinology, Biomedical Research Center, SAS, Bratislava, Slovakia. Contact e-mail: jozef.ukropec@savba.sk

ALLELIC DISTRIBUTION OF GENES FOR APOLIPOPROTEIN E AND MTHFR IN PATIENTS WITH ALZHEIMER’S DISEASE AND THEIR EPISTATIC INTERACTION

APOEε3 and APOEε4 whereof the latter increases the risk of disease 4-15 fold in a dose-dependent manner whilst APOEε2 appears to be protective. The biological mechanisms underlying the modified risk of disease in APOEε2 and APOEε4 carriers are not known. We previously showed that APOEε4carriers exhibit a prominent plasma apolipoprotein E (apoE) deficiency caused by a specific reduction of the apoE4 isoform. This apoE deficiency was not observed in cerebrospinal fluid. In cognitively intact APOEε3/ε4 carriers an increased relative ratio of plasma apoE4 to apoE3 correlated to glucose hypometabolism and gray matter volume reductions in brain areas most often affected in AD. Hence, we speculate that peripheral apoE levels are linked to processes driving the risk of developing AD brain pathology. In order to determine the cause of the observed phenotype of plasma apoE deficiency in APOEε4-carriers we aimed to investigate the expression of different APOE alleles in liver biopsies from individuals with an APOEε3/ε4 versus an APOEε2/ε3 genotype. Methods: Liver biopsies from liver explants were received from n1⁄43 APOEε3/ε4 and n1⁄43 APOEε2/ε3 carriers who had undergone liver transplantation at the Karolinska University Hospital in Sweden. Total RNA ( 80% in DV200 score) was isolated according to routine laboratory methods and used for RNA sequencing employing the high-throughput Illumina platform. Paired-end sequencing reads were aligned to the human reference genome (hg19), using TopHat, and gene counts for expression determined using HTseq-count. Differential expression between the genotype groups was calculated using DEseq2. Results: Preliminary analyses revealed differential expression of n1⁄4624 genes between individuals with an APOEε3/ε4 versus an APOEε2/ε3 genotype. Conclusions: In total n1⁄4624 genes are differentially expressed in livers from APOEε3/ε4 versus APOEε2/ε3 carriers. Further analyses will reveal the identity of the differentially expressed genes and whether there is a specific difference in the expression of APOE alleles that could explain the observed APOEε4 related plasma apoE deficiency

EFFECTS OF AEROBIC-STRENGTH TRAINING ON SELECTED MOLECULAR TARGETS IN CEREBROSPINAL FLUID OF SENIORS WITH MILD COGNITIVE IMPAIRMENT

Background:Cerebrospinal fluid (CSF) levels of total tau protein (hTau), phosphorylated tau (pTau181P), and amyloid-beta of 42 amino acids (Ab1-42) are established biomarkers for the diagnosis of Alzheimer’s disease (AD), but the discriminatory power for differential dementia diagnosis remains suboptimal. Also, current laboratory measures of CSF pTau181P are thought to underestimate the total levels of phosphorylated tau. The goal of this study is to investigate if the non-phosphorylated tau fraction (pTau rel) would improve the diagnostic performance of the routine AD biomarker panel for differential dementia diagnosis. Methods:The study population consisted of clinically diagnosed AD patients (n1⁄445), definite frontotemporal lobar degeneration (FTLD) patients (n1⁄445), definite Creutzfeldt-Jakob disease (CJD) patients (n1⁄420) and cognitively healthy controls (n1⁄420). CSF levels of Ab1-42, hTau, pTau181P and pTau rel were determined with commercially available single-analyte ELISA kits (INNOTEST b-Amyloid(142), INNOTEST hTau-Ag and INNOTEST Phospho-Tau(181P) from Fujirebio Europe, Belgium; pTAU rel ELISA Kit from AJ Roboscreen, IBL International GmbH, Germany). Receiver operating characteristic (ROC) curve analyses were used to obtain area under the curve (AUC) values. AUC values were compared using DeLong tests. Results:Diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. To evaluate the diagnostic power of pTau rel in the routine AD biomarker panel, the single (routine) marker with the highest AUC value was compared with that of pTau rel. Additionally, the (routine) biomarker ratio with the highest AUC value was compared with its equivalent using pTau rel. An overview of the results is listed in Table 1. Conclusions: The diagnostic performance of pTau rel for differential dementia diagnosis (comparing AD, FTLD, CJD patients and healthy controls) is not better than the diagnostic performance of the routine AD CSF biomarkers.