Poster Presentations: P4
California, United States; 3University of California Davis, Sacramento,
California, United States; 4Memory Clinic, UCSF, San Francisco,
California, United States. Contact e-mail: michael.weiner@ucsf.edu
Background: A significant obstacle to developing effective treatments
for Alzheimers disease (AD) is the cost of clinical trials. Valid
internet-based neuropsychological tests may reduce the costs to longitu-
dinally assess cognitively normal subjects who are at risk for cognitive
decline and to recruit these subjects into AD prevention trials. Memory
Match (LMM) is an online working memory game developed by Lumos
Labs. Although the validity of LMM scores as measures of working
memory has not yet been evaluated, longitudinal trends in LMM scores
may indicate declining performance due to aging or disease. Methods:
LMM learning rates, forgetting rates, and changes in the learning rates
over time can be estimated before subjects are enrolled in randomized
studies and used to predict decline, thus increasing statistical power,
reducing sample sizes, and lowering costs. With data provided by Lumos
Labs, the effects of age and time on learning and forgetting rates were esti-
mated with a mixed effects linear regression model. 2,212 Lumosity users
(ages, 40 - 79) played forty LMM game sessions following ten run-in ses-
sions for > 1 year. Sample sizes were calculated for 80% power to detect
slowing the rate of decline in the learning rate by 25% in 1 year trials for
subjects selected from the lowest quartile of learning rate change estimates
(decliners). Results: There were significant effects of age on lower initial
LMM scores (b -.39, P <.0001), lower initial learning rates (b -.0031,
P <.0001) and greater declines in learning rates over time (b -8.00E-06,
P < .001). Sample sizes as small as 136 subjects/arm were estimated for 1-
year trials using subjects in the lower quartile of learning rate decline.
Conclusions: The data suggest that declining learning rates are associated
with older ages and that recruiting subjects in the lower quartile of learning
rate decline significantly increases the statistical power to detect a treat-
ment effect in clinical trials. As such, our data support the potential use
of online memory games to identify subjects at risk for cognitive decline
with smaller sample sizes and lower cost than traditional recruitment
methods.
P4-319 APATHY MAY LEAD TO DEMENTIA IN PATIENTS
WITH PARKINSONS DISEASE
Annalena Venneri, Hamad Alzahrani, University of Sheffield, Sheffield,
United Kingdom. Contact e-mail: h.s.alzahrani@sheffield.ac.uk
Background: Apathy refers to a combination of behavioural, emotional
and cognitive features that lead to reduced interest and participation in
daily life activities. Apathy is considered one of the most common neuro-
psychiatric symptoms in Parkinsons Disease (PD). The prevalence of
apathy in PD is approximately 40%. Few studies have investigated the
cognitive and neuroanatomical correlates of apathy in PD. From apathy
studies in Alzheimers disease and other neurological disorders we ex-
pected to find deficits in frontal regions and in cognitive functions associ-
ated with frontal and temporal structures. Methods: Forty PD patients in
the early stages of the disease (18 with apathy and 22 without apathy) un-
derwent extensive neuropsychological screening, neuropsychiatric assess-
ment using the Neuropsychiatric Inventory, structural MRI scanning and
neurological examination. A voxel-based multiple regression analysis
was used to measure negative correlation between grey matter volumes
and apathy scores. Results: Higher apathy scores correlated with lower
grey matter volume in several brain areas including the left insula, left
inferior frontal gyrus, left middle frontal gyrus, left medial frontal gyrus,
right anterior cingulate and the left superior temporal gyrus. Patients with
apathy had lower scores in all cognitive tests. However, significant impair-
ments were found in tests assessing executive functions (Letter Fluency
Test and Stroop Test) and a trend-level significant difference was observed
in memory tests (Rey 15-word Memory Test and Category Fluency Test) in
patients with apathy when compared with patients without apathy. Con-
clusions: Apathy was associated with greater levels of atrophy in the fron-
tal cortex, temporal cortex and anterior cingulate as well as overall lower
level of cognitive performance, particularly in executive function and
P903
memory skills. These findings are in line with results from studies of other
neurological conditions. For instance, a similar pattern of executive
dysfunction has been reported in apathetic patients with PD with dementia
and apathetic patients with Alzheimer disease. Apathy appears to be a risk
factor for cognitive impairments in PD and might be a useful clinical indi-
cator of dementia risk in PD.
P4-320 NEUROPSYCHOLOGICAL ASSESSMENT OF
ADULTS WITH DOWN SYNDROME USING THE
CAMCOG-DS: A LONGITUDINAL COHORT
STUDY
Bessy Benejam1, Laura Videla2, Susana Fernandez2, Maria Carmona-
Iragui3, Sebastian Videla2, Juan Fortea4, 1Catalan Down Syndrome
Foundation, Barcelona, Spain; 2Catalan Down Syndrome Foundation,
Barcelona, Spain; 3Biomedical Research Institute Sant Pau, Barcelona,
Spain; 4Catalan Down Syndrome Foundation, Barcelona, Spain.
Contact e-mail: neuropsicologia@fcsd.org
Background: Dementia caused by Alzheimers disease (AD) commonly
affects the adult population with Downs syndrome (DS). However, AD
diagnosis represents a diagnostic challenge due to the intellectual
disability associated with DS and to a lack of appropriate instruments.
Methods: Prospective longitudinal 3 year cohort study. Forty-four
healthy DS were recruited from the Down Medical Centre. We included
only subjects with mild or moderate intellectual disability (ID) (DSM-IV
and ICD-10 criteria). Subjects with cognitive and/or functional decline at
baseline were excluded. Subjects underwent annual neuropsychological
assessments using CAMCOG-DS. An evaluation for progression to AD
was performed blinded to CAMCOG-DS scores. Results: Mean age at
baseline was 38.8 years (SD 10.14). Twenty-seven patients were males
(61.4%). Eighteen patients had mild ID (40.9%). CAMCOG-DS scores
at baseline were related to severity of ID, but were not related to gender
(p 0.43) or age (p 0.57). Subjects with mild ID scored higher on the
total CAMCOG-DS score at baseline than patients with moderate ID
(mean 83.9 vs 68.7; p < 0.001). At follow up, 10 patients developed
AD dementia. The repeated longitudinal CAMCOG-DS evaluation in
those subjects who progressed to AD dementia revealed an accelerated
rate of change in total CAMCOG-DS scores (mean change after 1, 2
and 3 years was -9.6, -12.33 and -22.4, respectively). Memory, language
and visual perception were the earliest cognitive domains affected. In
healthy DS subjects, total CAMCOG-DS scores remained stable. When
stratifying by age (< 40 and 40 years), only scores on memory CAM-
COG-DS subscale declined significantly in older healthy DS patients.
Conclusions: CAMCOG-DS is a sensitive neuropsychological battery
to assess cognitive decline in DS patients who progress to dementia.
However, cross-sectional CAMCOG-DS scores depend greatly on
severity of ID. Therefore, for AD diagnosis in DS subjects, individual
longitudinal change should be used.
P4-321 RELATIONSHIP BETWEEN THE EXCESS OF EEG
THETA ACTIVITY AND COGNITIVE
PERFORMANCE IN HEALTHY ELDERLY
SUBJECTS
Susana Angelica Castro Chavira1, Thala Fernandez2, Catalina Alatorre2,
Sergio Sanchez-Moguel2, Marisol Rincon3, Thala Harmony2,
Jimena Sandoval2, Marbella Espino4, 1Instituto de Neurobiologa,
Universidad Nacional Autonoma de Mexico, Queretaro, Mexico; 2Instituto
de Neurobiologa, UNAM, Queretaro, Mexico; 3Universidad Autonoma de
Queretaro, Queretaro, Mexico; 4Centro Estatal de Salud Mental, Secretara
de Salud del Estado de Queretaro, Queretaro, Mexico.
Contact e-mail: aquacreek@yahoo.com
Background: Excess of theta EEG activity predicts cognitive decline 7-10
years before its presentation (Prichep et al, 2006). NEUROPSI is a neuro-
psychological test normalized for the Mexican population that thoroughly
explores cognitive functions. Methods: Twenty eight right-handed
healthy subjects older than 60 years were selected. They have no
P904 Poster Presentations: P4

neurological or psychiatric disorders.Their blood count,cholesterol test, P4-323 VALIDATION OF THE CHINESE VERSION OF
triglycerides, glucose and TSH levels are normal, and their IQ is superior RELEVANT OUTCOME SCALE FOR
to 85.Their EEGs were recorded in the 19 leads of the 10-20 International ALZHEIMERS DISEASE (ROSA)
System, considering the short-circuited earlobes as reference. Z values of
Qihao Guo, Department of Neurology, Huashan Hospital, Fudan
Absolute Power corrected by Geometric Power were computed to separate
University, Shanghai, China. Contact e-mail: dr.guoqihao@126.com
the subjects into two groups: excess of theta (ET; n 16) or theta between
normal limits (NT; n 12). Differences between groups of the NEUROPSI Background: The Relevant Outcome Scale for Alzheimers disease
scores were analyzed using multivariate non-parametric permutation anal- (ROSA) is a novel observer rating scale developed for daily clinical practice,
ysis (Galan et al., 1998). Results: There were no differences between with characteristics of easy and quick administration, multi-domain assess-
groups in the sepatared cognitive processes (attention, memory coding ment, relevance for all AD severity stages, and suitability for long-term
or retrieval, language, reading comprehension, writing, or executive func- monitoring disease progression etc. This study was to verify the validity
tions). However, the ET group showed a significantly lower performance of the Chinese version of ROSA. Methods: The original English version
in the total score of the NEUROPSI test (p 0.05). Conclusions: There of ROSA included 16 items was translated into Chinese and back-translated
were no significant differences between subjects with EEG risk to develop to verify by the study group. A total of 332 outpatients diagnosed with prob-
cognitive decline (ET) and without EEG risk (NT) for any of the individual able AD according to the criteria of NIA-AA guideline were recruited and
cognitive processes evaluated. Furthermore, the subjects in both groups assessed with ROSA and other standard Chinese rating scales which
showed no cognitive deterioration. Even though the subjects with exces- frequently used for the assessments of AD. Construct and concurrent valid-
sive EEG theta activity did not express cognitive deterioration, their per- ities of the Chinese version of ROSA were measured. Correlations of the to-
formance was poorer than the performance of the subjects with normal tal score of ROSA with scores of single item, subscales, and the other
EEG. assessments were analyzed by Pearson correlation test or Spearman corre-
lation analysis. Results: The scores of each single item were significantly
correlated with the total score of ROSA (r-value range, 0.363-0.817, P <
0.01). The scores of six dimensions of ROSA, i.e., cognition (item 1-3),
P4-322 A SUITE OF DISCRIMINATION TASKS TO communication (item 4-6), behavior (item 7-11), function (item12-14),
BEHAVIORALLY ASSESS THE INTEGRITY OF quality of life (item 15) and caregiver burden (item 16) were highly corre-
HIPPOCAMPAL PATTERN SEPARATION AND lated with the total score of ROSA (r-value range, 0.638w0.855, P <
INDIVIDUAL DIFFERENCES IN 0.01). The score of ROSA was significantly correlated with the scores of
NEUROCOGNITIVE AGING Mini Mental State Examination, Mattis Dementia Rating Scale, and
Michael A. Yassa, Elizabeth Murray, Zachariah Reagh, Jared Roberts, Disability Assessment for Dementia (r0.441, 0.575, 0.346 respectively,
University of California, Irvine, Irvine, California, United States. P < 0.01), and significantly negatively correlated with the scores of Alz-
Contact e-mail: myassa@uci.edu heimers Disease Assessment Scale-cognitive, The Informant Questionnaire
on Cognitive Decline in the Elderly, Neuropsychiatric Inventory, and Zarit
Background: The hippocampus is a critical brain region for episodic Caregiver Burden Interview ((r-0.576, -0.540, -0.472, -0.346 respectively,
memory. It is hypothesized that one of its core computations is pattern P < 0.01). Conclusions: The Chinese version of ROSA is a valid and easy-
separation, the process of disambiguating similar neural inputs into administrative instrument to assess Chinese patients with AD and worth to
distinct orthogonal representations, a process that depends on the dentate be applied in the clinical practice and clinical studies.
(DG) and CA3 regions. We have previously shown that DG/CA3 pattern
separation is reduced in aging (manifesting as a functional rigidity in this
region), which is also linked to perforant path integrity as well as perfor- P4-324 UTILITY OF A NEUROPSYCHOLOGICAL
mance on neuropsychological tasks that involve fine-level discrimina- BATTERY FOR DISCERNING DEMENTIA WITH
tions among mnemonic representations. The latter approach continues LEWY BODIES FROM ALZHEIMERS DISEASE
to be neurobiologically validated, but it also expanded here to include Hajime Tabuchi, Mika Konishi, Daisuke Ito, Bun Yamagata, Mizuki Oka,
tasks that assess discrimination along several dimensions of memory (ob- Masaru Mimura, Keio University, Tokyo, Japan. Contact e-mail: tabuchi@
ject, spatial, temporal). Methods: In the object discrimination task, sub- a8.keio.jp
jects incidentally encode pictures and during test they view some of the
Background: Dementia with Lewy bodies (DLB), the second most com-
same items (targets), some new items (foils), and some similar items
mon cause of degenerative dementia after Alzheimers disease (AD), is
(lures). They are asked to make a recognition judgment. In the spatial
discrimination task, participants incidentally encode objects presented in
1 of 31 possible locations and during test they view the same objects Table 1
and asked to indicate whether the location of the items has changed Demographics and scores of the rating scales by stage of severity of AD
from study. Some items are presented in exactly the same location and (Mean6SD)
some are presented in different locations on the screen. In the temporal
discrimination task, participants incidentally encode objects in sequences Early stage Moderate stage Late stage
of 30 items and during are shown pairs of objects that were presented dur- Items n89 n162 n81 Total n332
ing study and asked to indicate which one was presented first. Results: We Age 70.53 (9.36) 70.58 (10.10) 68.59 (9.50) 70.08 (9.77)
show that older adults can exhibit one of two neuropsychological profiles ROSA 117.98 (21.27) 100.27 (24.62) 79.01 (23.38) 99.83 (27.24)
across all tasks: (1) mild deficits with a recovery (relative to young) at the MMSE 19.72 (2.15) 14.80 (2.89) 8.23 (3.41) 14.50 (5.01)
lowest levels of interference (aged-unimpaired AU), or (2) more severe DRS 113.73 (11.29) 88.99 (13.10) 66.11 (16.40) 90.71 (2.15)
deficits with no recovery even when interference is minimized (aged- ADAS- 28.70 (9.25) 40.42 (12.52) 53.72 (9.46) 53.71 (9.46)
impaired AI). Conclusions: We suggest that the AI group is likely more cog
susceptible to AD brain pathologies and propose that our tools can be IQCODE 63.83 (9.28) 68.63 (8.45) 75.95 (3.68) 69.11 (8.95)
used as an early diagnostic/risk marker. These translational tools bridge DAD (%) 84.75 (18.60) 82.86 (18.20) 60.19 (19.30) 77.78 (21.11)
from computational and animal models of episodic memory to human NPI 5.93 (4.90) 7.41 (4.69) 9.51 (5.78) 7.52 (5.18)
cognition and significantly expand our understanding of cognitive changes ZBI 33.35 (18.37) 37.19 (15.73) 38.20 (16.11) 36.38 (16.63)
in aging and Alzheimers disease.