J. Hort

Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer’s Disease

Background: Patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) have difficulties with spatial orientation. Objective: To test hypothesis that spatial navigation is impaired early in MCI patients representing the presymptomatic stage of AD. Methods: We tested patients with probable AD (n = 21), MCI, further classified according to Petersen’s criteria as amnestic MCI (aMCI) single domain (n = 11), aMCI multiple domain (n = 31), or nonamnestic MCI (n = 7). The aMCI group was also stratified using cued recall according to Dubois’ criteria into memory impairment of the hippocampal type (n = 10) and isolated memory retrieval impairment-nonhippocampal (n = 32) and also according to ApoE4 status into E4+ (n = 12) and E4– (n = 30). These patients and controls (n = 28) were tested in the human variant of the Morris water maze. Depending on the subtest, the subjects could use the egocentric or allocentric (hippocampus-dependent) navigation. Results: The AD and aMCI multiple domain groups were impaired in all subtests. The aMCI single domain group was impaired in allocentric subtests. The hippocampal MCI group performed poorer than the nonhippocampal MCI group and similarly to the AD group. The ApoE4+ group was as bad as the AD group when compared with the E4– group. Conclusion: aMCI subjects represent a very heterogeneous population, and spatial memory or cued recall examination can add more value to aMCI classification. ApoE4+ patients are more impaired than ApoE4– patients.

From Morris Water Maze to computer tests in the prediction of Alzheimer's disease.

Background: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer’s disease (AD). Objective: Contrast results from computer versus real-space versions of the HGT. Methods: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type – the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment – the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. Results: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. Conclusions: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

Real-space path integration is impaired in Alzheimer's disease and mild cognitive impairment.

INTRODUCTION Path integration (PI) is an important component of spatial navigation that integrates self-motion cues to allow the subject to return to a starting point. PI depends on the structures affected early in the course of Alzheimers disease (AD) such as the medial temporal lobe and the parietal cortex. OBJECTIVES To assess whether PI is impaired in patients with mild AD and amnestic mild cognitive impairment (aMCI) and to investigate the role of the hippocampus, entorhinal and inferior parietal cortex in this association. METHODS 27 patients with aMCI, 14 with mild AD and 18 controls completed eight trials of Arena Path Integration Task. The task required subjects with a mask covering their eyes to follow an enclosed triangle pathway through two previously seen places: start-place1-place2-start. Brains were scanned at 1.5T MRI and respective volumes and thicknesses were derived using FreeSurfer algorithm. RESULTS Controlling for age, education, gender and Mini-Mental State Examination score the aMCI and AD subjects were impaired in PI accuracy on the pathway endpoint (p=0.042 and p=0.013) compared to controls. Hippocampal volume and thickness of entorhinal and parietal cortices explained separately 36-45% of the differences in PI accuracy between controls and aMCI and 28-31% of the differences between controls and AD subjects. CONCLUSIONS PI is affected in aMCI and AD, possibly as a function of neurodegeneration in the medial temporal lobe structures and the parietal cortex. PI assessment (as a part of spatial navigation testing) may be useful for identification of patients with incipient AD.

EGOCENTRIC NAVIGATION IMPAIRMENT IS ASSOCIATED WITH FALL RISK IN OLDER ADULTS WITH NEURODEGENERATIVE DEMENTIA

P3-261 EGOCENTRIC NAVIGATION IMPAIRMENT IS ASSOCIATEDWITH FALL RISK IN OLDER ADULTS WITH NEURODEGENERATIVE DEMENTIA Jiri Cerman, Jan Lacz o, Martina Parizkova, Adela Fendrych Mazancova, Ondrej Cakrt, Jakob Hort, Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic; Diamant Neuropsychology Laboratory, Department of Neurology and Centre of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czech Republic; 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. Contact e-mail: arnoldator@ email.cz

THE EFFECT OF EARLY-STAGE ALZHEIMER’S DISEASE ON SPATIAL NAVIGATION STRATEGIES: A PILOT STUDY

pentagon drawing: t (53) 1⁄4 2.016, p < .05; for the four ADAS-Cog drawings: t (53) 1⁄4 2.89, p < .01. Subjects were able to copy designs with more accuracy on paper as compared to the tablet. Conclusions: Completing praxis tasks on a tablet computer resulted in significantly lower scores as compared to paper and pencil techniques. These methodologies do not seem to be equivalent. The subjects in this study were young, healthy normals and results with an older, demented population with less experience using tablet technology would presume to be increasingly detrimental. More research is needed to fully understand the impact of tablet technology on traditional assessment of cognition in Alzheimer’s disease.

SPIRITUAL WELL-BEING AS A PROTECTIVE FACTOR FOR THE EFFECT OF MEDIAL TEMPORAL LOBE ATROPHY ON MEMORY: DATA FROM CZECH BRAIN AGING STUDY

followed the cognitive stimulation program of memory training from AVAN center, during this study of eight weeks. None of them had previous experience with meditation or yoga. All participants underwent neurological and psychological evaluation before and after the 8 week intervention. Seven patients practiced KKM for 12 minutes daily, plus a weekly KY. The remaining eight subjects served as the control group. Results:The study group had an improvement in their depression scores and less anxiety compared to the memory training group alone (control), as shown by the Goldberg test. KKM group also expressed a significant improvement in their overall mood state, measured by the PEA test, for tension, hostility and confusion. The KKM group showed higher memory scores for their total free memory value as measured by the FCRST test, while the short form of Health Survey (SF-36) reflected a recovery in their social function. Conclusions: In subjects with MCI, our findings of enhanced cognition and psychological well-being suggest important improvements in quality of life, cognition, and well-being. Further studies are needed with a larger sample size to reinforce the efficacy of KKM in this population.

DISTINCT SPATIAL NAVIGATION IMPAIRMENT ACROSS NEURODEGENERATIVE DEMENTIAS AND ITS NEUROANATOMICAL UNDERPINNINGS

decline is increased substantially by the presence of at least one copy of the APOE ε4 allele. Despite advances in Ab biomarkers, age remains the greatest risk factor for dementia, particularly Alzheimer’s disease (AD). As APOE ε4 increases risk for Ab+ and older adults are also more likely to be Ab+, it is important to understand the extent to which age influences the effects of ε4 on Ab+ related memory decline. This study aimed to determine the extent towhich theAPOE ε4 allele influenced Ab related cognitive change in adults aged between 60-74 and 75-90 years old. Methods:Nondemented adults (n1⁄4485) enrolled in the AIBL study underwent Ab neuroimaging and ε4 genotyping. Episodic Memory was assessed at baseline, 18-, 36-, 54and 72-month follow-ups. Participants were classified as Abor Ab+ using PET neuroimaging and into two age groups (<75 and 75) according to their age at baseline. Data were analysed using linear mixed model analyses. Results:In adults aged<75, when compared to the Abgroup, there was a significant rate of memory decline only in Ab+ ε4 carriers (d1⁄41.25). In adults aged 75, when compared to the Abgroup, both Ab+ ε4 carriers (d1⁄41.23) and non-carriers (d1⁄40.35) showed significant rates of memory; however, the memory decline in Ab+ ε4 carriers was substantially greater when compared to noncarriers (d1⁄40.82). This faster rate of memory decline in adults aged 75 was reflected in a 43% of Ab+ ε4 carriers meeting clinical criteria for dementia at the 72-month assessment, in contrast to just 24% of Ab+ ε4 non-carriers and 10% of Abparticipants. Conclusions:Previous studies investigating the relationship between ε4 andAb+have not accounted for potential non-linear effects of age on memory decline. The rate of Ab+ related memory decline was greatest in adults aged 75, particularly in those who were also APOE ε4 carriers. This suggests that the combined effects of Ab+ and ε4 on risk for dementia increases substantially in older adults.

DIFFERENT SPECIFIC COGNITIVE COMPLAINTS REFLECT LOWER COGNITIVE PERFORMANCE AND DEPRESSIVE SYMPTOMATOLOGY IN COGNITIVELY NORMAL ELDERLY

REFLECT LOWER COGNITIVE PERFORMANCE AND DEPRESSIVE SYMPTOMATOLOGY IN COGNITIVELY NORMAL ELDERLY Hana Markova, Ross Andel, Hana Stepankova, Miloslav Kopecek, Tomas Nikolai, Jakob Hort, Martin Vyhnalek, International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic; Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; 3 School of Aging Studies, University of South Florida, Tampa, FL, USA; 4 National Institute of Mental Health, Klecany, Prague, Czech Republic. Contact e-mail: hanca.mar@seznam.cz

THE EFFECT OF APOE E4 ON EPISODIC MEMORY IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

P1-182 THEEFFECTOFAPOEE4ONEPISODICMEMORY IN PATIENTSWITHAMNESTICMILDCOGNITIVE IMPAIRMENT Ivana Mokrisova, Jan Laczo, Martina Parizkova, Kamil Vlcek, Martin Vyhnalek, Katerina Sheardova, Vojtech Kaplan, Vaclav Matoska, Ross Andel, Jakob Hort, Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; 2 International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic; Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 4 Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, Czech Republic; School of Aging Studies, University of South Florida, Tampa, FL, USA. Contact e-mail: mokrisova.ivana@gmail.com

SUBJECTIVE COGNITIVE COMPLAINTS REFLECT HIPPOCAMPAL ATROPHY IN NONDEMENTED OLDER ADULTS AS WELL AS OBJECTIVE MEMORY TESTING

Background: Self-reported subjective cognitive decline (SCD) could represent an early sign of Alzheimer’s disease (AD). Yet, the type of cognitive complaint associated with preclinical AD needs to be refined. We aimed at identifying specific types of complaint associated with i) medical help seeking, ii) the presence of actual memory impairment among patients referring to a memory clinic. We also assessed whether specific patterns of complaints were associated with neuroimaging biomarkers. Methods: We included three groups of nondemented elder individuals (Fig1): i) Healthy Aged Subjects (HAS, n1⁄461), ii) patients from a memory clinic with SCD but normal neuropsychological assessment (SCD, n1⁄429), iii) patients with amnestic Mild Cognitive Impairment (aMCI, n1⁄473). Participants filled the Cognitive Difficulty Scale questionnaire (CDS), consisting of 39 items on a 5-point scale. They underwent cognitive assessment, structural MRI and a subgroup had Florbetapir-PET to assess Ab burden. The questionnaire was analyzed in two complementary ways. First, between-group comparisons were conducted item-by-item using non-parametric tests to identify items related to medical help seeking (HAS<SCD) or cognitive impairment (SCD<MCI). Second, exploratory factor analysis was conducted on the full group, using a method adapted to ordinal data. Results: Compared to HAS, both SCD and MCI patient groups reported comparable complaint, mainly on attentional and memory items (Fig2, top). Only one item, assessing temporal orientation, discriminated between SCD and MCI patients; in the latter group, self-reported temporal disorientation was associated with worse memory and higher Ab burden (Fig2, bottom). The factor analysis identified 3 factors accounting for 54% of total variance. Factors 1 (general cognition/attention) and 2 (temporal orientation/memory) differed between groups (Fig 3, top) and were associated with anxiety but neither memory performances nor age. In MCI, the pattern of complaint depended on Ab status (fig 3, bottom): Ab+ patients reported strong orientation/memory difficulties and little attentional troubles while Abpatients had mixed complaints with a strong attentional component. Conclusions:Detailed assessment of patients’ self-reported difficulties is associated with clinical and cognitive features, as well as the presence of Ab in patients with MCI. Probing self-reported disorientation in addition to memory could have strong implications for early AD detection.