Bradley S. Glazier

Rats Self-Administer Carbachol Directly into the Nucleus Accumbens

The potential reinforcing effect of the muscarinic cholinergic agonist carbachol within the nucleus accumbens (ACB) was examined in female Wistar rats by using the technique of intracranial self-administration. Rats dose dependently self-administered solutions of 0.0-6.6 mM (in a volume of 100 nL per injection) directly into the ACB. Rats self-administered the 3.3 and 6.6 mM doses significantly more than the group given only vehicle. The caudate putamen did not support reliable self-administration of the 6.6-mM dose. Rats exhibited preference for the lever that produced infusions of 3.3 and 6.6 mM carbachol into the ACB over the lever that had no consequence. The self-infusion of the 6.6-mM dose into the ACB was inhibited by the coadministration of the muscarinic antagonist scopolamine (0.25 mM), but not by the nicotinic antagonist mecamylamine (6.6 mM). The present results suggest that direct activation of muscarinic receptors within the ACB supports self-administration and could result from reinforcement or from elicitation of a novel stimulus.

Early‐onset Dementia with Lewy Bodies

The clinical and neuropathological characteristics of an atypical form of dementia with Lewy bodies (DLB) are described. The proband experienced difficulties in her school performance at 13 years of age. Neurological examination revealed cognitive dysfunction, dysarthria, parkinsonism and myoclonus. By age 14 years, the symptoms had worsened markedly and the proband died at age 15 years. On neuropathological examination, the brain was severely atrophic. Numerous intracytoplasmic and intraneuritic Lewy bodies, as well as Lewy neurites, were present throughout the cerebral cortex and subcortical nuclei; vacuolar changes were seen in the upper layers of the neocortex and severe neuronal loss and gliosis were evident in the cerebral cortex and substantia nigra. Lewy bodies and Lewy neurites were strongly immunoreactive for α‐synuclein and ubiquitin. Lewy bodies were composed of filamentous and granular material and isolated filaments were decorated by α‐synuclein antibodies. Immunohistochemistry for tau or β‐amyloid yielded negative results. The etiology of this atypical form of DLB is unknown, since there was no family history and since sequencing of the exonic regions of α‐Synuclein, β‐Synuclein, Synphilin‐1, Parkin, Ubiquitin C‐terminal hydrolase L1 and Neurofilament‐M failed to reveal a pathogenic mutation. This study provides further evidence of the clinical and pathological heterogeneity of DLB.

Impaired traffic sign recognition in drivers with dementia

The determination of the safety of a patient with dementia who continues to drive is a difficult task for the physician who cares for geriatric patients. This study used the Traffic Sign Recognition Test (TSRT) discrimination between dementia patients who continue to drive and normal elderly volunteers. Thirty-seven subjects with dementia who continue to drive and 47 normal elderly volunteers were recruited to participate in the study. Each group was tested with the TSRT similar to that used for licensing in the state of Indiana. The difference in total number of signs correctly identified between the two groups was determined using the Wilcoxon Rank Sum Test. The difference between groups of each individual sign recognition was determined using a Chi Square test. The affected group was also tested with a neuropsychological battery (NB) designed to measure skills thought to be needed for driving. Drivers with dementia correctly identified 5.95 (± 2.17) of the 10 traffic signs used in licensing as compared to the normal elderly volunteers who correctly identified 8.77 (± 1.58) total signs (p < 0.0001). The “Slow Moving Vehicle” sign provided the largest difference between the two groups; demented drivers correctly identified the sign 39 percent of the time, compared with 89 percent in the normal volunteers (X2= 15.333, df= 1, p < 0.005). Only 76 percent of the demented drivers correctly identified a “Stop” sign compared with 98 percent of the normal elderly drivers. The percentage of correctly identified signs on the TSRT also correlated with several tests in the NB. Drivers with dementia who continue to drive perform worse on traffic sign recognition than normal elderly drivers. While our current screening tool did not assess the driving safety of either group, it suggests that demented patients who still drive may not recognize common traffic signs and may thus pose a risk to society.

Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging

Introduction: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET). Methods: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch. Results: We received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity. Over 88% of respondents had a positive response (∼10% with neutral and 2% with negative responses) to whether amyloid PET should be offered routinely and be reimbursed. Such information was felt to be useful for long-term legal, financial, and health care planning. Respondents identifying with early age cognitive decline (younger than 65 y) were more likely to explore options for disability insurance (P=0.03). Responders from the Midwest were more likely to utilize information from amyloid imaging for legal planning (P=0.02), disability insurance (P=0.02), and life insurance (P=0.04) than other US regions. Discussion: Patients and caregivers supported the use of amyloid PET imaging in clinical practice and felt that the information would provide significant benefits particularly in terms of future planning.

ANTICHOLINERGIC MEDICATION USE IS ASSOCIATED WITH REDUCED FMRI ACTIVITY DURING VISUAL EPISODIC ENCODING IN COGNITIVELY NORMAL OLDER ADULTS

responded ‘Never’, and for all but 2measures for this group tobe significantly different from every other one. As the frequency of reported usage increased, so did quality of performance, these improvements being incremental for measures from 7 tasks. On a pattern separation task, both speed and accuracywere significantly superior for the neurogenesis sensitive stimuli. The effect sizes of the differences between the 2 extreme scores were in the small tomedium range formeasures from 7 tasks. Conclusions: The frequency of word puzzle use is directly related to the quality of cognitive function on a range of major cognitive domains in this large population aged up to 96 years.

PATIENT AND CAREGIVER ASSESSMENT OF THE BENEFITS FROM THE CLINICAL USE OF AMYLOID-PET IMAGING

rater training using concrete behavioral anchors. Results:17 participants were recruited in two nursing homes, suffering from moderate to severe stages of dementia according to the Global Deterioration Scale. Multimodal sensor data and behavioral annotations were obtained for all 17 participants; videos were recorded for a subgroup of 8 participants during 29 consecutive days. Cohens Kappa of the video annotations was 0.75 for repetitive mannerisms, and 0.84 for pacing behavior. Further results will be presented at the conference. Conclusions:We obtained an extensive multimodal data set of naturally occurring challenging behavior in people with moderate to severe dementia. This data set was obtained in the routine setting of two nursing homes, in cooperation with nursing staff and scientists of different domains such as cognitive psychology, computer and nursing science and medicine. Using these data, sensor features will be developed to identify challenging behavior.

OPTIMIZING COGNITIVE CHANGE INDEX CUTOFFS BASED ON COGNITIVE DECLINE AND BIOMARKER POSITIVITY IN COGNITIVELY NORMAL OLDER ADULTS

and p value1⁄48.7 e-05 respectively). Furthermore a strong effect of baseline MMSE score on Adas0 (p value1⁄4 1e-10) was found. Conclusions:Our findings suggest that the presence of misidentification symptoms, either alone or as part of mixed presentation, increases the rate of progression, after controlling for potential confounding factors. These results support the hypothesis that psychosis subtypes have different cognitive trajectories.

ASSOCIATION BETWEEN N-BACK WORKING MEMORY ACTIVATION ON FMRI AND COGNITIVE ASSESSMENT OF EXECUTIVE FUNCTION

right hippocampi (r1⁄4-0.66,p<0.002; r1⁄4-0.68,p<0.002 respectively) as well as the left and right thalami (r1⁄4-0.66,p<0.002; r1⁄4-0.68,p<0.002 respectively). A weaker but similar relationship was observed in the control group, possibly due to a smaller population size (see Table 1). Figures 1.a,c show correlation coefficients overlaid on ICBM template for ventricular regions for the ex-CFL and control groups. Figure 1.b shows the significant FDR corrected p-value map for the ex-CFL cohort. Figures 2.a-c show similar images for subcortical regions. The color-coded bars in Figures 1.a-c and 2.a-c represent correlation coefficients values: warm colors correspond to regions of enlargement with age i.e. ventricles; cold colors correspond to areas negatively correlated with age i.e. hippocampi and thalami. Figure 2.b shows the significant regions after FDR correction in the ex-CFL. Table 1 shows correlation coefficients and FDR corrected p-values for the two groups for areas indicated by arrows. The uncorrected p-values for the control group did not survive FDR correction. Conclusions: Our results revealed extensive changes associated with age in the ex-CFL population. The changes predominantly involved volume decreases in the hippocampi and thalami, and volume increases in the ventricles. DBM may be a sensitive measure for detecting focal brain atrophy in patients that have suffered multiple concussions. IC-P-094 ASSOCIATION BETWEEN N-BACK WORKING MEMORYACTIVATION ON FMRI AND COGNITIVE ASSESSMENT OF EXECUTIVE FUNCTION John D. West, Shannon L. Risacher, Pratik K. Gandhi, YuChien Wu, Eileen F. Tallman, Brenna C. McDonald, Liana G. Apostolova, Martin R. Farlow, Jared R. Brosch, Darren P. O’Neill, Sujuan Gao, Steven A. Brown, Bradley S. Glazier, Frederick W. Unverzagt, Andy J. Saykin, 1 Indiana University School of Medicine, Indianapolis, IN, USA; 2 Indiana Alzheimer Disease Center, Indianapolis, IN, USA. Contact e-mail: jdwest@ iupui.edu

ASSOCIATION OF THE COGNITIVE CHANGE INDEX WITH HIPPOCAMPAL SUBFIELD VOLUMES

related to lower memory performance at baseline, whereas thinner temporal cortex was associated to subsequent decline of executive function (table 1). Conclusions: We found that thinner cortex in fronto-temporo-parietal regions is associated with subtle lower scores on memory function, while thinner temporal cortex is associated with an increased rate of decline in executive function. These findings suggest that subtle changes in the cortical mantle may precede clinical manifestation of AD.

SCENE ENCODING FMRI IN SUBJECTIVE COGNITIVE DECLINE

elwise analyses revealed widespread areas of hypometabolism (in lateral frontal, temporal, and parietal lobes) that were associated with less cognitive activity, and these regions overlapped partially the meta ROIs. Hippocampal volume was not correlated with cognitive activity in any age epoch. Conclusions: Cognitive engagement in early and midlife is associated with reduced amyloid, while current cognitive engagement is associated with reduced hypometabolism. These findings are consistent with proposed effects of early/midlife cognitive engagement on neural efficiency, but suggest that late life effects reflect other factors, such as cognitive reserve or reverse causation.