Differential effects of aging, Alzheimer’s pathology, andAPOE4on longitudinal functional connectivity and episodic memory in older adults DOI Creative Commons
Larissa Fischer, Jenna N. Adams, Eóin N. Molloy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract INTRODUCTION Both aging and Alzheimer’s disease (AD) affect episodic memory networks. How this relates to region-specific early differences in functional connectivity (FC), however, remains unclear. METHODS We assessed resting-state FC strength the medial temporal lobe (MTL) - posteromedial cortex (PMC) prefrontal network cognition over two years cognitively normal older adults from PREVENT-AD cohort. RESULTS within PMC between posterior hippocampus inferomedial precuneus decreased “normal” (amyloid- tau-negative adults). Lower was associated with poorer longitudinal performance. Increasing anterior superior related higher baseline AD pathology. Higher differentially trajectories depending on APOE4 genotype. DISCUSSION Findings suggest differential effects of pathology FC. MTL-PMC hypoconnectivity cognitive decline. Furthermore, hyperconnectivity decline carriers. Graphical abstract. A) “Normal aging” is characterized by a decrease connectivity. B) Cognitively unimpaired more at (measured via cerebrospinal fluid) exhibit increase

Language: Английский

Cerebral hyperactivation across the Alzheimer’s disease pathological cascade DOI Creative Commons
Nick Corriveau‐Lecavalier, Jenna N. Adams, Larissa Fischer

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 6(6)

Published: Jan. 1, 2024

Neuronal dysfunction in specific brain regions or across distributed networks is a known feature of Alzheimer's disease. An often reported finding the early stage disease presence increased functional MRI (fMRI) blood oxygenation level-dependent signal under task conditions relative to cognitively normal controls, phenomenon as 'hyperactivation'. However, research past decades yielded complex, sometimes conflicting results. The magnitude and topology fMRI hyperactivation patterns have been found vary preclinical clinical spectrum disease, including concomitant 'hypoactivation' some cases. These incongruences are likely due range factors, at which cohort examined, areas studied paradigm utilized evoke these abnormalities. Additionally, perennial question pertains nature context Some propose it reflects compensatory mechanisms sustain cognitive performance, while others suggest linked pathological disruption highly regulated homeostatic cycle that contributes to, even drives, progression. Providing coherent narrative for empirical conceptual discrepancies paramount develop models, understand synergy between cascade tailor effective interventions. We first provide comprehensive overview changes spanning course from ageing then highlight evidence supporting close relationship

Language: Английский

Citations

6

Differential effects of aging, Alzheimer’s pathology, andAPOE4on longitudinal functional connectivity and episodic memory in older adults DOI Creative Commons
Larissa Fischer, Jenna N. Adams, Eóin N. Molloy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract INTRODUCTION Both aging and Alzheimer’s disease (AD) affect episodic memory networks. How this relates to region-specific early differences in functional connectivity (FC), however, remains unclear. METHODS We assessed resting-state FC strength the medial temporal lobe (MTL) - posteromedial cortex (PMC) prefrontal network cognition over two years cognitively normal older adults from PREVENT-AD cohort. RESULTS within PMC between posterior hippocampus inferomedial precuneus decreased “normal” (amyloid- tau-negative adults). Lower was associated with poorer longitudinal performance. Increasing anterior superior related higher baseline AD pathology. Higher differentially trajectories depending on APOE4 genotype. DISCUSSION Findings suggest differential effects of pathology FC. MTL-PMC hypoconnectivity cognitive decline. Furthermore, hyperconnectivity decline carriers. Graphical abstract. A) “Normal aging” is characterized by a decrease connectivity. B) Cognitively unimpaired more at (measured via cerebrospinal fluid) exhibit increase

Language: Английский

Citations

0