Rosalinde E.R. Slot

Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer’s Disease in Non-Demented Elderly

BACKGROUND HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimers disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. OBJECTIVE To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. METHODS From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n = 206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n = 223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOEɛ4 carriership. RESULTS 117 patients (27%) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30% increased risk of clinical progression (hazard ratio (HR) (95% CI)  = 1.3(1.0-1.6)). The effect appeared to be attributable to the APOEɛ4 carriers with SCD (HR 3.3(1.0-10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEɛ4 carriers with SCD (HR 5.0(1.3-18.9)). CONCLUSION Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEɛ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.

Low normal cerebrospinal fluid Aβ42 levels predict clinical progression in nondemented subjects: CSF Amyloid and Progression

We studied whether continuous lower normal cerebrospinal fluid (CSF) amyloid β1‐42 (≥640pg/ml) levels were related with rate of clinical progression in a sample of 393 nondemented memory clinic patients. Lower normal levels were associated with faster clinical progression, and this depended on baseline cognitive status (subjective cognitive decline: hazard ratio [HR] = 0.57, p < 0.05; mild cognitive impairment: HR = 0.19, p < .01), indicating that normal CSF amyloid levels do not exclude incident Alzheimer disease. These findings suggest that research on preclinical markers for Alzheimer disease should take the continuum of CSF amyloid β1‐42 levels within the normal range into account. Ann Neurol 2017;81:749–753

Nutrients required for phospholipid synthesis are lower in blood and cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease dementia

Synaptic membrane formation depends on nutrients that fuel metabolic pathways for the synthesis of constituent phospholipids. Consequently, insufficient availability of such nutrients may restrict membrane formation and contribute to synaptic dysfunction in Alzheimers disease (AD). We assessed whether blood and cerebrospinal fluid (CSF) concentrations of nutrients related to phospholipid synthesis differ among patients with AD, mild cognitive impairment (MCI), and control subjects.

LONGITUDINAL CEREBROSPINAL FLUID BIOMARKER TRAJECTORIES ALONG THE ALZHEIMER'S DISEASE CONTINUUM: A MULTICENTRE EUROPEAN STUDY

years, range 0.5-3.4 years), statistically significant increases over time were noted in sAPPa, sAPPb, Ab38, YKL-40, NFL, p-tau, and decreases in Ab40, Ab42, MCP-1, and neurogranin (all p<0.004) Changes in biomarkers correlated with time since baseline visit (Figure). APOE4 status had little effect on biomarker changes over time. Conclusions: In this analysis of cognitivelyhealthy middle-aged and older adults enriched for AD risk, longitudinal CSF changes over several years suggest early neuropathologic changes that are discordant from cross-sectional assessments of CSF biomarker associations with age. Further longitudinal followup is underway to further characterize the impact of these CSF biomarker changes on cognition and other clinical endpoints.

A more randomly organized grey matter network is associated with deteriorating language and global cognition in individuals with subjective cognitive decline

Grey matter network disruptions in Alzheimers disease (AD) are associated with worse cognitive impairment cross‐sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD).

AMYLOID-β LOAD IS RELATED TO WORRIES IN INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE

O2-06-03 AMYLOID-b LOAD IS RELATED TO WORRIES IN INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE Sander C. J. Verfaillie, Tessa Timmers, Rosalinde E. R. Slot, Chris W. J. van der Weijden, Linda M. P. Wesselman, Niels D. Prins, Sietske A. M. Sikkes, Adriaan A. Lammertsma, Philip Scheltens, Rik Ossenkoppele, Bart N. M. van Berckel, Wiesje M. Van der Flier, VU University Medical Center, Amsterdam, Netherlands; Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands; Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands; Harvard Medical School, Boston University, Boston, MA, USA; Neuroscience Campus Amsterdam, Amsterdam, Netherlands; VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands; Lund University, Lund, Sweden; Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: s.verfaillie@vumc.nl

Wishes and preferences for an online lifestyle program for brain health—A mixed methods study

Individuals with subjective cognitive decline (SCD) are at increased risk of Alzheimers disease and could benefit from a prevention strategy targeting lifestyle factors. Making a program available through the Internet gives a widespread reach at low cost, but suboptimal adherence is a major threat to effectiveness. As a first step in developing an online lifestyle program (OLP), we aimed to identify factors that are barriers and/or facilitators for the use of an OLP in individuals with SCD in three European countries.

Computer-assisted prediction of clinical progression in the earliest stages of AD

Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression.

THE EFFECTS OF AMYLOID ON SEMANTIC COMPLEXITY IN SPONTANEOUS SPEECH IN SUBJECTIVE COGNITIVE DECLINE

tional standards (centiles) and conditional standards: AVLT Total Score. Three women who exhibit similar cognitive change are plotted on unconditional and conditional standards for the AVLT Total Score. Dotted 1⁄4 centiles(for women, average literacy, no college degree). Red 1⁄4 -1.5 SD conditional standard critical values (CVs) for scores CV. Green 1⁄4 CVs for scores >CV. Pink/violet 1⁄4 participants with one AVLT score below CVs; Blue 1⁄4 participant with all AVLTs above CVs. Values adjacent to colored lines indicate observed AVLT scores. Poster Presentations: Monday, July 17, 2017 P821

PROGNOSIS OF CLINICAL PROGRESSION IN SUBJECTIVE COGNITIVE DECLINE USING A CLINICAL DECISION SUPPORT SYSTEM

Ressources et de Recherche, Nice University Hospital, Nice, France; Tours University Hospital, Tours, France; CIC1401, Clinical Epidemiology, Bordeaux, France; CATI – Centre d’Acquisition et de Traitement des Images, Paris, France; Sorbonne Universit es, UPMC University, Paris 06, INSERM, CNRS, Institut du Cerveau et la Moelle (ICM), AP-HP Hôpital Piti e-Salpêtri ere, Paris, France; Centre INSERM U1219, Bordeaux, France. Contact e-mail: genevieve.chene@u-bordeaux.fr