Lower cerebral blood flow is associated with cognitive decline in patients with Alzheimer’s disease

Poster Presentations: IC-P

P57

Background: Cerebral blood flow (CBF) is lower in patient with Alzheimer’s disease (AD) compared to the general elderly population. We aimed to investigate whether lower CBF was associated with a more rapid cognitive decline in patients with AD. Methods: We included 88 AD patients from the Amsterdam dementia cohort, with an arterial spin labeling (ASL) scan at baseline and at least one year of clinical follow-up. 3T pseudo-continuous (PC-)ASL was used to determine whole brain and regional (parietal, frontal, occipital, temporal and cerebellar) CBF (ml/100gr/min). For statistical purposes, CBF was inverted (i.e., higher is worse) and standardized. Linear mixed models were used to determine associations between CBF and cognitive decline over time as measured with the MMSE. We adjusted for age, sex, education and normalized brain volume, and in a separate model additionally for white matter hyperintensities and lacunes. Results: Patients were 6567 years old, 44 (50%) were female and mean baseline MMSE was 2264. Mean follow-up of 2.160.8 years and patients declined with -2.263.0 MMSE points per year. Linear mixed models revealed no associations between whole brain or regional CBF with baseline MMSE (table 1). One standard deviation (SD) lower whole brain CBF was associated with a steeper decline of 0.5 MMSE points per year (Model 1: b[SE] -0.50[0.25], p¼0.05). In particular, lower parietal CBF was associated with steeper annual decline on the MMSE (Model 1: b[SE] -0.59[0.25], p<0.05). Lower occipital CBF tended to be associated with cognitive decline as well (Model 1: b[SE] - 0.47[0.25], p¼0.06). Additional adjustment for white matter hyperintensities and lacunes did not change these results. CBF in frontal, temporal and cerebellar regions was not associated with cognitive decline. Conclusions: Lower CBF, in particular in the parietal lobes, is associated with a steeper decline on the MMSE. These findings indicate that CBF as measured with ASL may have value as prognostic marker for cognitive decline in patients with AD.

Table 1 Associations of CBF with baseline MMSE and with annual change in MMSE. Model 1

Cerebral blood flowx Whole brain Parietal Frontal Temporal Occipital Cerebellum

IC-P-079

LOWER CEREBRAL BLOOD FLOW IS ASSOCIATED WITH COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMER’S DISEASE

Marije Benedictus, Annebet Leeuwis, Joost Kuijer, Philip Scheltens, Frederik Barkhof, Wiesje M. van der Flier, Niels Prins, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: m.benedictus@ vumc.nl

Model 2

Estimated baseline MMSE

Estimated Estimated annual change baseline in MMSE MMSE

Estimated annual change in MMSE

-0.3260.39 -0.5060.41 -0.0260.43 -0.2060.39 -0.2960.38 0.2660.39

-0.50+0.25U -0.59+0.25* -0.1460.26 -0.4660.25 -0.47+0.25* -0.1860.26

-0.4910.25U -0.59+0.25* -0.1260.26 -0.4760.25 -0.47+0.25* -0.1760.26

-0.2860.39 -0.45+0.41 0.1260.43 -0.17+0.39 -0.2360.39 0.3060.40

Data are represented as (b6SE. Linear mixed models were used to investigate associations between CBF and change in MMSE. A random intercept and random slope for time (in years) were assumed. The model includes terms for the CBF measure, time, the interaction between the CBF measure and time and covariates. The given b; in each first column represents the difference in baseline MMSE.In each second column, the b represents the difference in annual MMSE change. Negative values indicate that a lower CBF is associated with a decline in MMSE. Model 1: adjusted forage, sex, education and NBV Model 2: additional adjustment for WMH and lacunes *: p< 0.05 U p¼0.05 # : p¼0.06 x :CBF was inverted (i.e., higher is worse) and given per SD deviation increase (worsening)