Tracy L. Ohrt

3 RATE OF UNDIAGNOSED COGNITIVE IMPAIRMENT IN COMMUNITY SETTINGS: IS THERE A NEED FOR SCREENING?

The Midwest Initiative for Dementia Screening (MINDS) Project, funded by Extendicare Foundation, proposed to improve early detection of previously undiagnosed cognitive impairment in community-dwelling individuals through memory screenings and educational lectures. Our goals were first to assess the rate of undiagnosed cognitive impairment and to provide appropriate referral information for individuals in need of further evaluation. The community screenings were not intended to provide diagnoses but rather to identify individuals in need of a clinical evaluation. Still, participants with limited access to neuropsychological services were provided with a summary of screening data sufficiently extensive to serve the purpose of a clinical evaluation. The data could be used by a primary care provider (PCP) within the context of a comprehensive clinical diagnostic evaluation. We provided memory screenings for 260 individuals, screened at one of eight locations around southern Wisconsin. Of those screened, 203 (78%) were women with a mean age of 77 years. Male participants had a mean age of 83 years. Of the 260 individuals screened, 129 (50%) showed no evidence of cognitive impairment, scoring at or above the normal range on cognitive tests. Testing also confirmed a previous diagnosis of a memory disorder for 24 individuals (9%). The remaining 107 (41%) individuals demonstrated varying degrees of cognitive impairment on testing, presumably undetected. Performance on screening tests was considered with medical history and current medications. Based on the totality of information gathered, we suspected that 35 individuals demonstrated cognitive impairments in multiple cognitive domains and that the deficits were not adequately explained by other medical conditions or concurrent treatments. These individuals (33% of the 107) subsequently received a recommendation for a full diagnostic workup to determine if their screening performances were the result of a neurodegenerative disease such as Alzheimers dementia. The 30 individuals (28% of the 107) demonstrating focal memory impairment on screening measures, not attributed to other medical conditions or treatments, were referred for further evaluation to assess for a mild cognitive impairment. The remaining 42 (39%) were encouraged to discuss issues such as medications, depression, and anxiety with their PCP and monitor their condition. We also compared the Mini Mental Status Exam (MMSE) scores of all participants with the results of their full memory screening performance. A score of 24 or lower on the MMSE was considered impaired. Of the 260 participants, 21 (8%) scored in the impaired range on the MMSE. Twelve of those participants had their memory disorder confirmed by our testing, leaving 9 of the remaining 248 participants (4%) scoring in the impaired range. PCPs often rely on a MMSE to quickly gauge the cognitive functioning of patients and alert them to impairment. However, our findings indicate that only 8 individuals (7%) of the 107 suspected here to have cognitive impairment demonstrated impairment on the MMSE. In other words, the cognitive decline in 93% of the participants who demonstrated impairment on our testing would have gone unnoticed if the MMSE was relied on as the sole screening method. The MINDS project revealed that older adults residing in the community are indeed interested in participating in memory screenings. Consistent with previous reports, nearly half demonstrated some level of cognitive impairment, warranting follow-up evaluation. Furthermore, data gathered in similar screenings could be used by PCP in communities where there is limited access to neuropsychological services, reducing reliance on the MMSE as the only tool to assess cognition.

P-113: 4 point clock drawing task is superior to the Mini Mental Status Exam for detection of cognitive impairment in community memory screenings

Neala J. Lane, Tracy Ohrt, David Baker, Naoko Yura Yasui, Sanjay Asthana, Carey Gleason, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA; Geriatric Research, Education, and Clinical Center Wm S. Middleton Memorial VA Hospital, Madison, WI, USA; University of Wisconsin-Madison, Graduate School, Madison, WI, USA; University of Wisconsin-Madison, School of Education, Madison, WI, USA. Contact e-mail: njl@medicine.wisc.edu

10 AN ANALYSIS OF PATIENTS' INTEREST IN RESEARCH FROM A MEMORY SPECIALTY CLINIC

Purpose Successful recruitment of subjects into clinical research trials is one of the most difficult tasks facing research centers. As the prevalence of many diseases continues to increase, the need for research into effective treatments and potential cures for these diseases has become critical. As the pressures of subject recruitment have accordingly reached a crucial level, it has become necessary to re-evaluate the potential resources for recruitment. One such resource for subject recruitment is specialty clinics whose primary focus is the disease under investigation. In order to achieve a practical estimation of the potential number of subjects to be enrolled, however, a realistic examination of the population that presents to specialty clinics of this nature is required. Methods We performed an analysis on patient visits over the course of one year in a geriatric specialty memory clinic in Madison, Wisconsin. Results Data revealed that the majority of patients (67%) who presented to this clinic were poor clinical research candidates. Reasons for consideration as a “poor candidate” include lack of evidence for a dementia diagnosis, transportation and/or caregiver burdens, severity of impairment, and comorbid medical conditions. Of the remaining clinic patients seen over the course of one year, 40% were eligible and interested in participating in research; however only 14% of the eligible population was enrolled into clinical research studies. Though this is higher than the 2002 CenterWatch Data, which stated that less than 10% of the eligible population of volunteers participate in clinical trials, it is a source of concern. Conclusions Of those patients seen over one year in a dementia specialty clinic, only a small proportion was enrolled in clinical research. These findings have serious implications for the continued success of clinical trials, but may be aided by the development of a collaborative relationship between researchers and clinicians to foster a model forum for the presentation of research opportunities to eligible participants. Recommendations for the development of such networks will be addressed in detail.

The effects of gender on the relationship between body mass index and CSF AB42 and tau levels

the M-CSF receptor (M-CSFR). We previously showed that increasing expression of the M-CSFR on cultured microglia dramatically upregulates microglia M-CSF and IL-1 expression. Objectives: To determine if knockdown of microglial interleukin-1 and M-CSF expression affects NMDA-induced neurotoxicity in a co-culture system. Methods: We used a co-culture model consisting of microglia overexpressing the M-CSFR and hippocampal organotypic cultures treated with the neurotoxin NMDA. To test the importance of microglial IL-1 and M-CSF on neuronal survival, we used an shRNA gene-targeted approach in which we selectively and without toxicity deleted microglial IL-1 or M-CSF expression prior to co-culture assembly. Transfections were performed with the hairpin RNA expression plasmid pGSU6-GFP-shRNA. To quantify neuronal injury, we used propidium iodide as well as FluoroJade staining. Results: We found that when microglia overexpressing the M-CSFR were cocultured with organotypic slices, there was complete protection of neurons from NMDA-induced injury. However, after knockdown of either microglial IL-1 or M-CSF, neuroprotection was abolished. Using TaqMan real-time RT-PCR, we confirmed that the shRNA constructs resulted in a 75% knockdown of cytokine expression. Both M-CSF and IL-1 were necessary for microglial proliferation, but only IL-1 removal also suppressed chemotactic migration of microglia toward the NMDA-injured organotypic culture. Conclusions: These results demonstrate that IL-1 and M-CSF are essential for M-CSFR-induced microglial neuroprotection in a microglial-organotypic hippocampal co-culture system. In AD, increased IL-1 and M-CSF expression by M-CSFR-activated microglia could actually serve to protect, rather than harm neurons. It may be that some inflammatory factors expressed early in AD could be beneficial, so that suppressing inflammation might accelerate rather than prevent disease progression. (Supported by an Alzheimer’s Association New Investigator Award to O.M. and NIH award MH57833).