Biology subjects

Remz, J.

Publications and source records attributed to Remz, J..

3 recordsLinked to original sources

bioRxiv2025

Longitudinal functional connectivity during rest and task is differentially related to Alzheimer's pathology and episodic memory in older adults

Changes in functional connectivity (FC) strength involving the medial temporal lobe (MTL) and posteromedial cortex (PMC) are related to early Alzheimers pathology and alterations in episodic memory performance in cognitively unimpaired older adults, but their dynamics remain unclear. We examined how longitudinal changes in FC involving MTL and PMC during resting-state, episodic memory encoding, and retrieval relate to subsequent amyloid- and tau- PET burden, longitudinal episodic memory performance, and the APOE4 genotype in 152 cognitively unimpaired older adults from the PREVENT-AD cohort. We found APOE4- and fMRI paradigm-dependent associations of change in FC strength with pathology burden and change in episodic memory performance. Decreasing FC over time, or "hypoconnectivity", within PMC during rest in APOE4 carriers and during retrieval in APOE4 non-carriers was related to more amyloid and tau, respectively. Conversely, increasing FC over time, or "hyperconnectivity", within MTL during encoding in APOE4 carriers and between MTL and PMC during retrieval independent of APOE4 status was related to more tau. Further, increasing FC between MTL and PMC during rest, unlike during encoding, was beneficial for episodic memory. Our study highlights that pathology-related episodic memory network changes manifest differently during rest and task and have differential implications for episodic memory trajectories.

neuroscience↗

bioRxiv2024

Differential effects of aging, Alzheimer's pathology, and APOE4 on longitudinal functional connectivity and episodic memory in older adults

INTRODUCTIONBoth aging and Alzheimers disease (AD) affect episodic memory networks. How this relates to region-specific early differences in functional connectivity (FC), however, remains unclear. METHODSWe assessed resting-state FC strength in the medial temporal lobe (MTL) - posteromedial cortex (PMC) - prefrontal network and cognition over two years in cognitively normal older adults from the PREVENT-AD cohort. RESULTSFC strength within PMC and between posterior hippocampus and inferomedial precuneus decreased in "normal" aging (amyloid- and tau-negative adults). Lower FC strength within PMC was associated with poorer longitudinal episodic memory performance. Increasing FC between anterior hippocampus and superior precuneus was related to higher baseline AD pathology. Higher FC strength was differentially associated with memory trajectories depending on APOE4 genotype. DISCUSSIONFindings suggest differential effects of aging and AD pathology on longitudinal FC. MTL-PMC hypoconnectivity was related to aging and cognitive decline. Furthermore, MTL-PMC hyperconnectivity was related to early AD pathology and cognitive decline in APOE4 carriers. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/627967v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@12c0cc9org.highwire.dtl.DTLVardef@fb7c6borg.highwire.dtl.DTLVardef@a56bdforg.highwire.dtl.DTLVardef@4d1773_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract.C_FLOATNO A) "Normal aging" is characterized by a longitudinal decrease in functional connectivity. B) Cognitively unimpaired older adults with more Alzheimers pathology at baseline (measured via cerebrospinal fluid) exhibit a longitudinal increase in functional connectivity. C_FIG

neuroscience↗

bioRxiv2024

Precuneus activity during retrieval is positively associated with amyloid burden in cognitively normal older APOE4 carriers

The precuneus is an early site of amyloid-beta (A{beta}) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated A{beta}. However, longitudinal studies in early Alzheimers disease (AD) risk stages are lacking and the interaction with Apolipoprotein-E (APOE) genotype is unclear. In the PREVENT-AD cohort, we assessed how precuneus activity during successful memory retrieval at baseline and over time relates to future A{beta} and tau burden and to change in memory performance. We further studied the moderation by APOE4 genotype. We included 165 older adults (age: 62.8{+/-}4.4 years; 113 female; 66 APOE4 carriers) who were cognitively normal at baseline and had a family history of AD. All participants performed task-fMRI at baseline and underwent 18F-flortaucipir-PET and 18F-NAV4694-A{beta}-PET on average 5 years later. We found that higher baseline activity and greater longitudinal change in activity in precuneus were associated with higher subsequent A{beta} in APOE4 carriers but not non-carriers. There were no effects of precuneus activity on tau burden. Finally, APOE4 non-carriers with low baseline activity in the precuneus exhibited better longitudinal performance in an independent memory test compared to APOE4 non-carriers with high baseline activity and APOE4 carriers. Our findings suggest that higher task-related precuneus activity at baseline and over time are associated with subsequent A{beta} burden in cognitively normal APOE4 carriers. Our results further indicate that the absence of hyperactivation and the absence of the APOE4 allele is related with the best future cognitive outcome in cognitively normal older adults at risk for AD. Significance StatementThe precuneus is a brain region involved in episodic memory function and is an early site of amyloid-beta (A{beta}) accumulation. Alterations in task-related activity occur in the precuneus with ageing as well as with Alzheimers disease (AD) pathology even in the absence of cognitive symptoms; however, their course and implications are not well understood. We demonstrate that higher precuneus activity at baseline and its change over time during successful memory retrieval is associated with higher A{beta} burden on average 5 years after baseline in Apolipoprotein-E4 (APOE4) carriers. Lower precuneus baseline activation was related to better memory performance over time in APOE4 non-carriers. Our findings provide novel longitudinal evidence that increased activity in posterior midline regions is linked to early AD pathology in dependence of APOE4 genotype.

neuroscience↗