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Background: Neurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer's disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship. Method: Resting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants' APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates. Result: Plasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871). Conclusion: Our results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer's disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship. Method: Resting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants' APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates. Result: Plasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871). Conclusion: Our results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia. [ABSTRACT FROM AUTHOR]

Background: The 'cingulo‐opercular' network (CON) functional connectivity (FC) decreases in aging and mild cognitive impairment. However, little is known about the cross‐sectional differences or longitudinal changes in CON FC in subjective cognitive decline (SCD). Frontal white‐matter tracts such as the forceps minor exhibit alterations in SCD and, thus, might play a relevant role for CON FC in SCD. Thus, we tested (i) whether baseline SCD predicts CON FC decrease over three years and (ii) whether white matter in the forceps minor modulates that effect. Method: Sixty‐nine healthy older participants (13 males; 68.33 ± 7.95 years old) underwent resting‐state functional and diffusion‐weighted magnetic resonance imaging. Forty‐nine of those participants were further enrolled in 2 follow‐ups, about 18 months apart each. The degree of SCD was assessed at baseline with the memory functioning questionnaire (MFQ; greater score indicating more SCD). After imaging data preprocessing, we obtained the average CON FC (correlation between 5 regions) for each time point and the neurite density of the forceps minor ('structural connectivity', SC), which was then averaged across time points. A latent growth curve model was fit to the longitudinal FC data, setting the intercept at the last time point. The model tested whether baseline MFQ predicted FC after 3 years (latent intercept) and/or its rate of change (latent slope) and whether the interaction between SC and MFQ predicted the latent intercept of FC. Result: We did not find evidence of baseline MFQ as a predictor of CON FC after 3 years (b = ‐0.19, 95% confidence interval, CI, [‐0.49, 0.11], p = 0.211) or its rate of change (b = ‐0.17, [‐0.37, 0.03], p = 0.093). However, we found that SC (averaged across all time points) modified the relation between MFQ and FC after 3 years (intercept, b = 0.20, [0.03, 0.37], p = 0.020; FIG). Conclusion: Greater SCD predicts lower CON FC after 3 years in individuals with relatively low neurite density in the forceps minor. This evidence implies that CON FC alterations in SCD are dependent upon the forceps minor's white matter and that these alterations might be associated with attentional or executive‐function changes in SCD. [ABSTRACT FROM AUTHOR]

Functional MRI (fMRI) is a key tool for investigating neural underpinnings of cognitive development. Yet, in recent years, the reliability of fMRI effects has come into question and with it, the feasibility of using task-based fMRI to identify developmental changes related to cognition. Here, we investigated the reliability of task-based fMRI activations with a widely used subsequent memory paradigm using two developmental samples: a cross-sectional sample (n = 85, age 8–25 years) and a test-retest sample (n = 24, one-month follow up, age 8–20 years). In the large cross-sectional sample, we found good to excellent group-level reliability when assessing activation patterns related to the encoding task and subsequent memory effects. In the test-retest sample, while group-level reliability was excellent, the consistency of activation patterns within individuals was low, particularly for subsequent memory effects. We observed consistent activation patterns in frontal, parietal, and occipital cortices, but comparatively lower test-retest reliability in subcortical regions and the hippocampus. Together, these findings highlight the limitations of interpreting task-based fMRI effects and the importance of incorporating reliability analyses in developmental studies. Leveraging larger and densely collected longitudinal data may help contribute to increased reproducibility and the accumulation of knowledge in developmental sciences. • Reliability of fMRI memory encoding was assessed in cross-sectional and test-retest developmental samples. • Subsequent memory effects were less consistent than activations across all encoding trials, regardless of memory outcome. • Group-level effects showed excellent consistency in both cross-sectional and test-retest reliability analyses. • Individual test-retest reliability was good in cortical regions but lower in subcortical regions and the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) can predict the progression to mild cognitive impairment. Visual memory deficits in mildly impaired patients relate to decreased activity in brain regions beyond the medial temporal lobe, such as the parahippocampal place area (PPA). PPA's response to visual scenes is weaker in healthy older than younger adults but equally associated with memory recognition. PPA's response to scenes' perceptual details during encoding might support that association. Whether perceptual detail processing is reduced in SCD can help elucidate the disparity between perceived decline and normal performance. Here we test whether older adults with SCD ('SCD') use perceptual details to a lesser extent than older adults without SCD ('CON') and whether this is observed during the encoding or retrieval of a scene memory task. Methods: We measured BOLD‐fMRI activity in 37 healthy older adults (SCD: 16) during encoding, and calculated hit rate, false alarm rate, and total recognition accuracy during retrieval. We analyzed BOLD‐fMRI activity during scene encoding in PPA. PPA was defined based on a functional Neurosynth meta‐analysis of studies including the term "place" and further constrained to the lingual and posterior parahippocampal gyri, and posterior‐temporal and temporal‐occipital fusiform cortices. Scenes' perceptual details were quantified as the number of unique objects in it (high‐load: > 4; low‐load: < 4). Results: During encoding, PPA activity was higher for high‐load than low‐load scenes (P = 2.08e‐06) but did not differ between SCD and CON (P =.763), indicating comparable encoding of perceptual details across groups. Nevertheless, during retrieval, SCD appeared to benefit significantly less from perceptual details than CON (P =.018), as their false alarm rates were similar for high‐ and low‐load scenes (P =.879), whereas CON's were significantly lower for high‐load than low‐load scenes (P =.002). Conclusions: Although tentative, our results suggest that SCD encode perceptual details similar to CON but use details to a lesser extent than CON when new information must be differentiated from old information during retrieval. Accordingly, memory complaints in SCD may reflect the perception of a 'lower‐resolution' retrieval, especially in the face of new information. [ABSTRACT FROM AUTHOR]

Background: Older adults are at high risk for both cognitive decline and social isolation. A higher level of social interaction, however, confers a protective effect against cognitive decline, and intervention studies have demonstrated the efficacy of social interactions to enhance cognitive function. The biological mechanism of this enhancement is unclear. Here we evaluate the association between social interaction and the functional connectivity of the salience (SN) and default mode (DMN) networks, two large‐scale brain networks implicated in social and cognitive function. Method: Michigan Alzheimer's Disease Center at University of Michigan (Ann Arbor, MI, USA) collected data on the Lubben Social Network Scale (LSNS‐6), which indicates levels of social interaction, and resting‐state functional MRI data for 62 older adults with normal cognition (NOR; mean age +/‐ SD = 69.72 years +/‐ 6.24) and 51 mild cognitively impaired (MCI; 71.61 years +/‐ 8.57) participants. We evaluated the association between SN or DMN functional connectivity (DV) and level of social interaction using a linear regression model with age and sex as covariates. Result: NOR and MCI participants did not differ in age (t=‐1.31, p=0.19), level of social interactions (t=1.47, p=0.14), or SN connectivity (t=1.86,p=0.065), but MCI did have lower DMN connectivity (t=2.839, p=0.005). Level of social interaction associated positively with SN connectivity (t=2.34, p=0.02, rp=0.218). The Lubben items most strongly associated with SN connectivity were: "How many relatives do you feel at ease with that you can talk about private matters?" (rp=0.268, p=0.004) and "How many relatives do you feel close to such that you could call on them for help?" (rp=0.284, p=0.003). Conclusion: Our data support an association in older adults between greater salience network connectivity and higher levels of social interaction, driven by quality of family interactions. Notably, an association with level of social interaction was not found for default mode network connectivity, suggesting the association found with salience network is not a global network effect. This finding highlights salience network functional connectivity as a meaningful outcome measure for social interventions on cognition in older adults. [ABSTRACT FROM AUTHOR]

The article discusses the personality traits and moods associated to early incidence of Alzheimer's disease (AD).