S2-01-03

S180

Symposium S2-02-01: Biomarkers/Imaging

associated with cognitive decline measured over a 14-year period on one or more cognitive tests. The changes were emerging at baseline but became highly reliable over the period of prospective evaluation. These observations provide further support for the hypothesis that vascular risk factors make later-life dementia more likely. Supported by: NHLBI Contracts N01-HC55015 to N01-HC-55022 and R01-HL70825 S2-01-02

COGNITIVE RESERVE

Yaakov Stern, Taub Intitute, Columbia University College of Physicians and Surgeons, New York, NY, USA. Contact e-mail: [email protected] The concept of cognitive reserve (CR) posits that individual differences in how tasks are processed provide differential reserve against brain pathology or age-related changes.. Epidemiologic evidence suggests that individuals with greater CR, as indicated by higher IQ, education, occupational attainment or participation in leisure activities, have slower age-related cognitive decline and a reduced risk of developing Alzheimer’s disease (AD). Imaging studies have begun to identify the neural substrate of CR, and suggest that it may be mediated by more efficient flexible neural networks. CR is an important consideration in the early detection and treatment of AD. Finally, directly enhancing reserve may help forestall age-related cognitive changes and the clinical onset of AD. S2-01-03

CLINICAL PATH

concurrent Alzheimer pathology having a more Alzheimer type clinical profile during life. Similarities and differences between DLB and dementia that develops during Parkinson’s disease have been determined. Sensitivity of clinical diagnostic criteria to case detection remains low, particularly because core clinical features such as fluctuating cognitive impairment and assessment of mild degrees of Parkinsonism remain problematic and poorly defined. Imaging has made a major contribution to facilitating accurate recognition and delineating DLB from other types of dementia. Characteristic imaging changes include preservation of medial temporal lobe on MR, parieto-occipital hypoperfusion on SPECT and PET (which appears to relate to visual perceptive dysfunction and hallucinations) and dopaminergic abnormalities on SPECT and PET imaging. A recent multicentre European study of dopaminergic (FP-CIT) SPECT imaging found a sensitivity of 78% and specificity of 90% when distinguishing DLB from non DLB dementia (predominantly Alzheimer’s disease) and this is now a licensed investigational product within the EU. Progress has also been made in terms of earlier and more accurate recognition of fluctuation and the recent revision of DLB consensus criteria incorporates these new findings with the aim of both improving the sensitivity of the clinical criteria and allowing case detection much earlier in the course of the disease process than is currently possible. S2-01-05

GENETIC AND ENVIRONMENETAL FACTORS

Albert Hofman, Erasmus University, Rotterdam, The Netherlands. Contact e-mail: [email protected] Abstract not available.

David A. Bennett, Rush University Medical Center, Chicago, IL, USA. Contact e-mail: [email protected] The clinical condition we call AD results from numerous genetic and environmental risk factors that cause, add to, or interact with multiple neuropathologic and neurobiologic indices leading to cognitive impairment. Thus, an important step in understanding the disease comes from longitudinal clinical-pathologic studies that can simultaneously examine the role of amyloid deposition, tangle formation, infarcts, Lewy bodies, and other post-mortem indices on the expression of AD and cognitive impairment. The availability of information on risk factors for clinical AD and cognitive decline in studies that include post-mortem indices provides an opportunity to examine biologic pathways that link risk factors to the expression of disease. For example, while some risk factors appear to be related to clinical AD through associations with amyloid and tangles, others appear to be related to clinical AD through associations with cerebral infarctions, and still others through post-mortem indices that have not yet been identified. The overall approach informs on strategies for disease prevention, and offers the opportunity to identify new molecular targets for therapy. S2-01-04

NEUROIMAGING IN THE DETECTION AND ASSESSMENT OF LEWY BODY DISEASE

John T. O’Brien, Newcastle University, Newcastle upon Tyne, United Kingdom. Contact e-mail: j.t.o’[email protected] Dementia with Lewy bodies is the second most common cause of degenerative dementia in older people and is clinically characterized by the triad of fluctuating cognition, recurrent visual hallucinations and spontaneous Parkinsonism. Accurate and early detection of DLB is important because psychotic symptoms in such patients respond preferentially to cholinesterase inhibitors. Antipsychotics need to be avoided because of serious adverse sensitivity reactions while patients have a complex picture of cognitive, psychiatric, motor and autonomic features, each of which require careful assessment and management. Consensus clinical diagnostic criteria developed a decade ago represented a major initial step in terms of improving ante mortem diagnosis. Since then, however, much progress in the field has been made. The importance of overlap of Lewy and Alzheimer pathology has become clearer, with cases characterized by substantial

MONDAY, JUNE 11, 2007 SYMPOSIUM S2-02 BIOMARKERS/IMAGING S2-02-01

MRI AND CSF ANALYSIS PROBE DIFFERENT STAGES OF AD AND HAVE COMPLEMENTARY VALUE

Philip Scheltens, Wiesje Van der Flier, Frederik Barkhof, Niki Schoonenboom, VU University Medical Center, Amsterdam, The Netherlands. Contact e-mail: [email protected] Background: Decreased amyloid ␤ (1-42) (A␤42) and increased (phosphorylated) tau in cerebrospinal fluid (CSF) are considered to be a reflection of plaques, tangles, and neuronal degeneration in Alzheimer’s disease (AD). Atrophy of the medial temporal lobe (MTA) on magnetic resonance imaging (MRI) reflects neuronal loss in this area. Objective(s): To compare diagnostic accuracy of CSF biomarkers and MTA in AD versus controls. Methods: A␤42, tau and tau phosphorylated at threonine 181 (Ptau-181) were measured in CSF from 61 AD patients and 32 controls by sandwich enzyme-linked immunosorbent assay. A CSF biomarker profile for AD was constructed. MTA was rated visually on MRI. Results: When AD patients and controls were evaluated separately, no correlations were present between the CSF markers and MTA score. Both MTA and CSF biomarker profile were independently associated with the diagnosis AD (MTA: OR (95% CI) ⫽ 28 (3 - 239); CSF biomarker profile: OR (95% CI) ⫽ 57 (13 - 262)). Among individuals younger than 65 years old and without MTA 60% suffered AD; in this group, the finding of an abnormal CSF biomarker profile was limited to AD patients only. Conclusions: MTA and CSF biomarkers seem to be of incremental value for the diagnosis AD. CSF analysis is most sensitive in the absence of MTA, and especially among early-onset AD patients. S2-02-02

PET

Mony J. de Leon, New York University School of Medicine, New York, NY, USA. Contact e-mail: [email protected] Abstract not available.