Cerebellar and cerebral grey and white matter volumes: The Rotterdam study

S68 IC-P-148

CP: Preconference for Physicians and Clinicians CEREBELLAR AND CEREBRAL GREY AND WHITE MATTER VOLUMES: THE ROTTERDAM STUDY

Yoo Young Hoogendam, Jos van der Geest, Albert Hofman, M. Arfan Ikram, Meike Vernooij, Monique Breteler, Erasmus MC, Rotterdam, Netherlands. Background: In research about aging of the brain, many researchers have showed an interest in supratentorial atrophy. Although population-based studies have widely investigated structural properties of the cerebrum, the cerebellum has received little attention. Studies in the general population on structural properties of the cerebellum are scarce. In a population-based study of community dwelling elderly we sought to investigate properties of the cerebellum to create normative estimates; to study the relationship with age and sex; and to study the interrelationship with cerebral volumes. Methods: The study is based on the Rotterdam Scan Study, an ongoing population-based cohort study investigating age-related brain changes on MRI. We included 3962 persons (mean age 60.2 years (SD 8.6), 54.4% women) with complete MRI scans. Cerebellar and cerebral volumes were calculated using Freesurfer1. We used linear regression analyses to calculate the relationship between age, sex, and volumetric properties of the cerebellum and cerebrum. Results: Average intracranial volume was 1491.0 mL. Cerebellar volume was 134.3 mL in men and 122.4 mL in women. Cerebellar grey matter volume was 102.8 mL and white matter volume was 25.0 mL. Mean cerebral grey matter was 437.1 mL, white matter was 455.1 mL. The ratio of grey and white matter in the cerebellum showed a difference between males and females (p < 0.001). This was not found for the cerebrum (p ¼ 0.56). Age-related volume loss was 0.24 mL per year for cerebellar grey matter (p < 0.001), and 0.11 mL per year for cerebellar white matter (p < 0.001). In the cerebrum the volume loss per year was 0.96 mL (p < 0.001) for grey matter and 1.54 mL for white matter (p < 0.001). Conclusions: Cerebellar and cerebral volumes are larger in men than in women. The ratio of grey and white matter volumes is different for cerebellum and cerebrum. Cerebellar grey matter showed a larger age-related decline than cerebellar white matter, while in the cerebrum, a larger volume loss was found in white matter tissue. These data can serve as a reference for future studies on cerebellar volumes. 1. Fischl, B. et al. 2002. Neuron 33, 341-355. IC-P-149

ARTERIAL STIFFNESS IS ASSOCIATED WITH CEREBRAL SMALL VESSEL DISEASE

Mohammad Ikram1, Keren Zaccai1, Mari€elle Poels2, Germaine Verwoert1, Meike Vernooij1, Jacqueline Witteman1, Aad van der Lugt1, Francesco MattaceRaso1, Monique Breteler1, 1Erasmus MC, Rotterdam, Netherlands; 2Erasmus MC University Medical Center, Rotterdam, Netherlands. Background: Arterial stiffness, as measured by aortic Pulse Wave Velocity (aPWV), is a novel marker of cardiovascular damage and has been associated with cardiovascular disease. Recent studies have also investigated the association with cerebral small vessel disease. However, because most studies were conducted in small samples or pre-selected populations, the results have been inconsistent. In a large cohort study of community-dwelling elderly we investigated the association between arterial stiffness and cerebral small vessel disease. Methods: From the Rotterdam Study 1460 participants (45 years of age and older) underwent aPWV measurement and a brain MRI scan. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI-analysis we obtained volumes of grey matter, white matter, and white matter lesions. Brain infarcts (cortical or lacunar) and microbleeds (lobar or deep) were rated visually according to location. We used linear and logistic regression models to investigate the association between aPWV and brain MRI markers. All analyses were adjusted for age, sex, mean arterial pressure and heart-rate and additionally for relevant cardiovascular risk factors. Subsequently, we stratified the analyses by presence or absence of hypertension. Results: In the total population higher aPWV was associated with a smaller grey matter volume, and larger white matter lesion volume, but not with brain infarcts or microbleeds. In contrast, after stratification by hypertension we found that higher aPWV was significantly asso-

ciated with larger white matter lesion volume (difference in standardized volume per SD increase in aPWV 0.12 (95% CI0.02;0.22), and higher prevalence of lacunar infarcts (OR per SD increase in a PWV 1.54 (1.00-2.36) and deep microbleeds (OR 1.83 (1.11;3.02)). Among persons without hypertension we did not find any significant associations with brain infarcts or microbleeds. Conclusions: We found that arterial stiffness is associated with markers of cerebral small vessel disease; the associations were most pronounced in persons with hypertension. IC-P-150

EEG-DERIVED BIOMARKERS OF NORMAL AGERELATED CHANGE IN EPISODIC MEMORY

Kerry Kilborn1, Stephanie Connell1, Zoe Tieges2, Eniko Zsoldos1, 1 Glasgow University, Glasgow, United Kingdom; 2University of Edinburgh, Edinburgh, United Kingdom. Background: In healthy older adults, changes in cognition, including memory, attention, and various executive functions, may be due to normal brain aging. However, not all functions change at equal rates, and some may remain quite robust. This uneven pattern of change contributes to the difficulty in differentiating normal age-related change from pathological deficits, such those caused by incipient Alzheimer’s disease. In this study, we explore the application of functional biomarkers derived from a non-invasive measure of brain function to characterize change in episodic memory function in healthy older (50 - 85 years) adults. Methods: Participants were healthy volunteers of mid - (50-65 years, mean age 59, N ¼ 50) and older age (67-85 years, mean age 79, N ¼ 50). The two groups did not differ on mean MMSE and GDS scores. Subjects performed a computerized, cross-modal “old/new” memory task, while scalp potentials were recorded using 128channel EEG. In the task, paired associates consisting of a simple image and a spoken word were presented simultaneously. Subjects pressed a button on each trial to indicate whether each stimulus pair was previously presented (old) or not (new). Old items were divided into two categories, corresponding to either a short (5 intervening items) or long (39 intervening items) interval from the first (new) presentation. Results: Memory performance (d’and response latency) of the younger group was significantly better than the older group. There was a significant Memory x Age interaction on the prefrontal P400 amplitude, due to a larger difference between groups on long items. The anterior-central N200 peak latency was significantly shorter for the younger group (178ms) than for older group (188ms). ERPs also revealed memory but not age effects on the anterior N200 amplitude and P600 amplitude. Conclusions: Two cognitive ERP effects: an anterior-central N200, associated with executive function, and a prefrontal P400, associated with episodic encoding, varied as a function of age. In contrast, the N200 and P600 amplitudes were sensitive to memory demands, but did not vary with age. Our findings suggest that ERP measures can differentiate specific age-related changes in episodic and attentional functions from more general memory load effects. IC-P-151

MYELIN INTEGRITY MEDIATES AGE-RELATED SLOWING IN COGNITIVE PROCESSING SPEED IN A SAMPLE OF HEALTHY ELDERLY MEN

Po-Haong Lu1, Grace Lee1, Erika Raven1, Theresa Khoo1, Kathleen Tingus1, Jim Mintz2, Paul Thompson1, George Bartzokis1, 1 UCLA, Los Angeles, California, United States; 2UT Health Science Center, San Antonio, Texas, United States. Background: To assess the hypothesis that in a healthy elderly population, age-related slowing in cognitive processing speed is mediated by myelin breakdown in regions that myelinate later in brain development (late-myelinating white matter; LMwm) and are highly vulnerable to the effects of aging. Methods: An in vivo MRI biomarker of myelin integrity (transverse relaxation rate; R2) for LMwm (composite of prefrontal lobe white matter and genu of the corpus callosum) was obtained for 35 healthy elderly men (mean age ¼ 66.8 years; sd ¼ 5.8; range ¼ 55-76). Cognitive processing speed (SPEED) was measured using the Trailmaking Test. Data analysis aimed to determine how much of the association between age and SPEED was accounted for by the posited mediator, LMwm R2. The paths were estimated using regression and multiple regression analyses. Mediation