#24
Federica Agosta

Amyloid Related Imaging Abnormalities (ARIA) in Amyloid Modifying Therapies: risk factors, symptomatology and monitoring recommendations

Abstract:

Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer’s disease, successfully reducing amyloid-β and decelerating cognitive deterioration. Nevertheless, these treatments are associated with amyloid-related imaging abnormalities (ARIA), including swelling (ARIA-E) and bleeding (ARIA-H). Both ARIA-E and ARIA-H may manifest early during anti-amyloid-β monoclonal antibody treatment. In randomized controlled trials, most ARIA were asymptomatic, with symptomatic ARIA-E often occurring at higher doses and resolving upon stopping the treatment. Comprehending the underlying mechanisms and risk factors related to ARIA can guide better treatment strategies and enhance patient outcomes. Key risk factors for ARIA-E and ARIA-H include the Apolipoprotein E genotype and treatment dosage. The presence of microhemorrhages on baseline MRI increases the likelihood of ARIA development. Given the substantial risk/benefit ratio of monoclonal antibodies and the impact of ARIA, MRI is crucial for patient selection and safety monitoring. Custom neuroimaging classification systems for ARIA have been developed, and ongoing education for prescribers and imaging raters is imperative. This ensures the effective identification and management of potential ARIA cases, reducing risks to patients. In conclusion, although anti-amyloid immunotherapies offer significant advantages in treating Alzheimer’s disease, they also pose the risk of ARIA. Through meticulous patient selection, ongoing education, and standardized monitoring protocols, the risks can be controlled, ensuring that patients receive the maximum benefit from these therapies while minimizing potential adverse effects.

#25
Emrah Düzel

Targeting dysfunction in episodic memory circuitry in Alzheimer’s disease

Abstract: Alzheimer’s Disease causes pathology to spread along neural circuits that serve specific cognitive processes, such as pattern separation and pattern completion and familiarity recognition. On the basis of data from the DZNE DELCODE cohort, I will discuss how amyloid and tau pathology impact on synaptic function in these circuits and to what extent dysfunction can be observed in the absence of MRI visible neurodegeneration. These data have implications on the question whether synaptic function can partially recover after amyloid removal with disease modifying anti-amyloid treatments. Building on these observations, I will discuss how non-pharmacological interventions can be used to unlock reserve mechanisms in conjunction with amyloid-removal. Our data indicate that cognitive reserve can be associated with the ability to activate upstream visual areas and midline cortical areas of the episodic memory circuitry. Individuals who maintain high levels of encoding related activation in these areas can cope with hippocampal atrophy, amyloid and tau-pathology, such that they show slower cognitive decline in memory over several years of follow-up. I will discuss approaches for brain stimulation of these regions as well as cognitive training interventions targeting these regions to potentially improve cognitive reserve mechanisms and help individuals to better maintain cognitive performance.

Keywords: Amyloid pathology, neurodegeneration, episodic memory, synaptic dysfunction, anti-amyloid treatments, cognitive reserve, brain reserve, non-pharmacological interventions

#26
Gaël Chételat

Enhancing Brain Health: The Preventive Potential of Meditation against Neurodegenerative Diseases

Abstract: Psychological and psycho-affective factors play a crucial role in the risk for Alzheimer’s disease (AD), with both negative and positive psychological traits impacting disease progression. Notably, depressive symptoms, even subclinical, are associated with lower brain integrity, while positive traits such as self-reflection, purpose in life, and optimism are linked to decreased AD risk. The Medit-ageing European consortium, funded by the European Commission, explores the potential of meditation to enhance brain health and prevent neurodegenerative diseases. The interest in meditation as a mental training approach for aging stems from its potential to directly influence both negative and positive psychological factors.

This presentation outlines the consortium’s research, focusing on two clinical trials sponsored by Inserm: SCD-Well and Age-Well. SCD-Well evaluated the effects of an 8-week meditation program versus an health education intervention on behavioral and blood measures in 147 patients with subjective cognitive decline (SCD). Age-Well comprised a cross-sectional study of 25 older expert meditators and an 18-month intervention study in 137 cognitively unimpaired older adults randomized in three arms (meditation, foreign-language learning and a no-intervention passive control) and assessed with behavioral and biological (i.e. blood, neuroimaging and sleep) measurements. Results of the two clinical trials will be presented including the impact of meditation intervention on the primary outcomes and on several secondary outcomes. According to the Medit-Ageing model proposed by the Consortium, mindfulness and loving kindness and compassion meditation act synergistically to counter adverse aging factors and promote beneficial ones, through attention control, deconstructive, and constructive mechanisms. The presentation will also disclose preliminary findings in the older expert meditators to test this model; as well as the application of artificial intelligence-based brain age models to assess the impact of meditation expertise on brain age. Overall, findings suggest that meditation holds promise as a protective lifestyle intervention for aging, impacting both negative and positive psychological factors associated with AD risk. The talk concludes with insights into ongoing research efforts and future directions, including the development of a meditation app tailored for older individuals and the exploration of longer-term meditation’s impact on various health markers.

Authors: Gael Chételat¹, Fabienne Collette², Julie Gonneaud¹, Olga Klimecki³, Géraldine Poisnel¹, Antoine Lutz⁴, Natalie L. Marchant⁵; for the Medit-Ageing Research Group.

 ¹ Normandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France.

² GIGA-CRC, In Vivo Imaging, Université de Liège, Liège, Belgium and Belgian National Fund for

Scientific Research.

³ Swiss Center for Affective Sciences, Department of Medicine, University of Geneva, Geneva, Switzerland.

⁴ Lyon Neuroscience Research Center INSERM U1028, CNRS UMR5292, Lyon 1 University, Lyon, France.

⁵ Division of Psychiatry, University College London, London, United Kingdom.

#27
Simon Cox

Dementia and Cognitive Ageing in the Lothian Birth Cohorts

Abstract: The Lothian Birth Cohort 1936 is a longitudinal study of 1091 older adults born in 1936 and living in the Edinburgh and Lothians area of Scotland who sat – along with all 11-year-old Scottish schoolchildren – a test of cognitive ability in 1947. I will provide a brief overview of the studies including the ongoing triennial assessments, and the recently-completed clinical dementia ascertainment over a period of ~17 years. Notably, no participants had a neurodegenerative diagnosis at recruitment (age 70), and I will summarise research from the team to identify structural neuroimaging and cognitive predictors of subsequent dementia risk. We also use the valuable longitudinal data to test the hypothesis that distinct factors increase dementia risk via cognitive intercept (preserved differentiation) or cognitive decline (differential preservation).

Keywords: cognitive ageing, dementia, risk factors, Lothian Birth Cohort, structural neuroimaging.

Speaker: Professor Simon R. Cox on behalf of the LBC research team.

Affiliation: Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, UK

#28
Eider Arenaza-Urquijo

From the individual to the environment: understanding cognitive and brain resilience in aging

Abstract: There is a significant potential for dementia prevention by addressing modifiable risk factors that are believed to foster brain resilience across the lifecourse, including physical activity and mental health related factors. While emphasis has been on individual efforts to modify risk and resilience in the context of dementia, the urban environment’s influence on shaping behaviors is increasingly recognized. We will present results from a series of studies focused on cognitively unimpaired older adults at increased risk of cognitive decline combining lifestyle, mental health, cognitive, imaging and CSF data. The studies suggest a long-lasting association of lifelong individual behaviors and risk factors exposure with biomarkers of aging and Alzheimer’s in late life. Specifically, our results demonstrate that both changes in physical activity during midlife and exposure to stressors across the life course correlate with multiple pathways including, brain structure, amyloid, tau pathologies and markers of neuroinflammation. Then, we will introduce a framework that shifts the focus from individual factors to the influence of social factors and urban environment. This will be exemplified by the funded UBRAIN project aimed to understand the role of urban environment, including walkability and urban stress, in influencing physical activity, mental health and ultimately brain resilience, in older adults with and without cognitive impairment.
Together, we will emphasize the importance of understanding risk and resilience considering different life stages as well as factors operating at various levels including those related to the individual and the environment.

Keywords: prevention, lifestyle, Alzheimer’s disease, urban health, mental health

Author: Eider M. Arenaza-Urquijo, PhD, Institute for Global Health, ISGlobal, Barcelona, Environment and Health over the Lifecourse Programme.