No abstract

Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.

Objectives: Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults. Method: Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week. Results: Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume. Conclusions: Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.

Background: Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear.Methods: Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking.Results: Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels).Conclusions: Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors.

Background White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase risk of developing mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, less is known about the extent and pattern of WMH in pre‐MCI stages, such as among those with objectively‐defined subtle cognitive decline (Obj‐SCD). Therefore, we aimed to examine regional WMH volume in Obj‐SCD versus those who were cognitively normal (CN) and MCI. Method Six hundred twenty‐one Alzheimer’s Disease Neuroimaging Initiative participants (182 CN; 96 Obj‐SCD; 343 MCI) underwent neuropsychological testing and MRI exams. Cerebrospinal fluid (CSF) data were available for ∼50% of the sample. MCI was classified using Jak/Bondi criteria and Obj‐SCD was classified using criteria proposed by Thomas et al. (2018, 2020). ANCOVA models were used to compare cognitive groups on regional WMHs adjusting for age, sex, and apolipoprotein E (APOE) ɛ4 status. We also ran analyses stratified by CSF phosphorylated tau (p‐tau)/amyloid‐β (Aβ) ratio positivity versus negativity. Result Compared to the CN group, those with Obj‐SCD had greater frontal (p=.036) and temporal WMH (p=.034) with a trend toward greater occipital WMH (p=.052). Those with MCI had greater frontal, temporal, parietal, and occipital WMH (p’s <.01). No significant differences in WMH volume were observed between Obj‐SCD and MCI (p’s >.05). Among p‐tau/Aβ negative individuals, those with Obj‐SCD showed a trend toward greater temporal WMH (p=.053) compared to CN individuals. In addition, the p‐tau/Aβ negative MCI participants showed significantly higher frontal (p=.001), temporal (p=.004), and parietal (p=.027) WMH relative to the CN group. Among p‐tau/Aβ positive individuals, there were no significant group differences in WMH volume. Conclusion Regional WMH vary across cognitive groups. Compared to the CN group, the Obj‐SCD group showed higher temporal and frontal WMH whereas the MCI group showed more widespread WMH increases affecting all lobes, which is in line with their greater cognitive impairment. Notably, these findings do not appear to be driven by p‐tau/Aβ positive individuals. Findings add to growing evidence of associations between Obj‐SCD and imaging biomarkers, providing support for utility of our criteria to capture very subtle cognitive changes.