Inverse association between the anticholinergic burden and hippocampus volume in a population-based cohort across the entire adult age range

Many medications of different indications have a relevant anticholinergic activity. The anticholinergic burden of medication has been shown to have significant effects on the cognition and the risk for cognitive impairment and dementia particularly in older patients. So far, most of the studies used data from geriatric patients and the effect of the anticholinergic burden on brain structures is still unexplored. Our study aimed to analyze possible associations of hippocampus and cholinergic basal forebrain volumes as vulnerable brain structures for the development of dementia and the anticholinergic burden in a population-based cohort of non-demented participants spanning the adult age range from 21 to 80 years. We analyzed associations between medication-related anticholinergic burden and structural MRI volumes from participants (n = 3087, 52.2% female) of the population-based “Study of Health in Pomerania” (SHIP). Anticholinergic burden was obtained from the current medication plan using the Anticholinergic Burden Scale (ACB). All analyses were adjusted for age, sex, education, and total intracranial volume. We found statistically significant associations between the ACB and the left and right hippocampus volume but not for the basal forebrain cholinergic system. Complementary voxel-based analysis across all participants revealed FWE-corrected (p = < 0.05) clusters in the temporo-parietal regions reaching into frontal areas, showing reduced volumes with higher ACB scores. We identified an association between anticholinergic burden of medication on hippocampal volume suggesting a potential inverse effect of such medication. This association highlights the importance of a careful prescription of medication with anticholinergic activity at any adult age.

Change in hippocampal volume in children with febrile seizure at different periods

Background This study aimed to investigate the change of hippocampal volume in children at different periods after febrile seizure. Methods MRI of the brain was performed in 60 children with febrile seizure (30 patients with simple febrile seizure and 30 patients with prolonged febrile seizure) and in 30 healthy children. The volume of the hippocampus was tested and compared at different periods after febrile seizure. Results The volumes of hippocampus in the two febrile seizure groups increased compared with that of the control group in acute period after seizure. There was no obvious difference in hippocampal volume between the simple febrile seizure group and the prolonged febrile seizure group in the acute or chronic period after seizure. The average annual growth of hippocampal volume in the simple febrile seizure group was greater than that in the prolonged febrile seizure group. Conclusions Febrile seizure can affect hippocampus volume in the acute stage of convulsion. Prolonged febrile seizure affects hippocampus development with aging.

The Diagnostic Value of Multi Ultra High-b-value DWI for Alzheimer’s Disease

To evaluate the diagnostic value of multi-ultra high b-value diffusion-weighted imaging (UHBV-DWI) in Alzheimer’s disease (AD), and to build a regression prediction modelfor AD.90 participants including 30 AD, 30 mild cognitive impairments (MCI) and 30 volunteers without neurological diseases were enrolled to perform with hippocampal volume, white matter hyperintensities volume (WMH volume), periventricular white matter hyperintensity (PVWMH) score, deep white matter hyperintensity (DWMH) score and UHBV-DWI.We found UHBV-DWI outperformed in the diagnosis of AD (AUC = 0.858), and multiple linear regression model: y = 0.515 + 0.018 *(WMH volume) + 0.221 *(ADCuh value)-0.359 *(left hippocampus volume) were established.So we came to a conclusion: UHBV-DWI is helpful for diagnosing AD, and the combination of WMH volume and left hippocampus volume has a better diagnostic performance.

Regional brain volumes relate to Alzheimer’s disease cerebrospinal fluid biomarkers and neuropsychometry: A cross-sectional, observational study

We hypothesized that automated assessment of brain volumes on MRI can predict presence of cerebrospinal fluid abnormal ß-amyloid42 and Tau protein levels and thus serve as a useful screening test for possible Alzheimer’s disease. 113 participants ranging from cognitively healthy to Alzheimer’s disease underwent MRI exams to obtain measurements of hippocampus, prefrontal cortex, precuneus, parietal cortex, and occipital lobe volumes. A non-exclusive subset (n = 107) consented to lumbar punctures to obtain cerebrospinal fluid for ß-amyloid42 and Tau protein assessment including cognitively health (n = 75), mild cognitively impaired (n = 22), and Alzheimer’s disease (n = 10). After adjustment for false discovery rate, ß-amyloid42 was significantly associated with volumes in the hippocampus (p = 0.043), prefrontal cortex (p = 0.010), precuneus (p = 0.024), and the posterior cingulate (p = 0.002). No association between Tau levels and regional brain volume survived multiple test correction. Secondary analysis was performed to determine associations between MRI brain volumes and CSF protein levels to neuropsychological impairment. A non-exclusive subset (n = 96) including cognitively healthy (n = 72), mild cognitively impaired (n = 21), and Alzheimer’s disease (n = 3) participants underwent Stroop Interference and Boston Naming neuropsychological testing. A higher score on the Boston Naming Test was optimally predicted in a selective regression model by greater hippocampus volume (p = 0.002), a higher ratio of ß-amyloid42 to Tau protein levels (p < 0.001), greater posterior cingulate volume (p = 0.0193), age (p = 0.0271), and a higher education level (p = 0.002). A better performance on the Stroop Interference Test was optimally predicted by greater hippocampus volume (p = 0.0003) and a higher education level (p < 0.001). Lastly, impaired cognitive status (mild cognitive impairment and Alzheimer’s Disease) was optimally predicted in a selective regression model by a worse performance on the Stroop Interference Test (p < 0.001), a worse performance on the Boston Naming Test (p < 0.001), along with lower prefrontal cortex volume (p = 0.002) and lower hippocampus volume (p = 0.007).

Relationship Between Oxytocin Levels and Brain Volume in Anorexia Nervosa Compared to Healthy Controls

Background: A disruption in food motivation pathways has been described in females with anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low weight. We have shown that in AN and healthy controls (HC), levels of oxytocin (OXT), a hormone involved in lactation, social behavior and weight regulation, decrease after a meal. In HC, we identified a relationship between postprandial change in OXT and subjective appetite, yet this association was absent in females with AN, suggesting a disconnect between OXT and appetite regulation in AN. Prior studies have shown that gray matter volume of the amygdala and hippocampus, areas rich in OXT receptors, correlate with OXT levels in HC. Furthermore, these regions play a central role in food reward and decreased volume has been reported in AN. We hypothesized that the relationship between postprandial change in OXT and amygdala and hippocampal gray matter volume would differ between AN and HC. Methods: We performed a cross-sectional study of 51 females (23 restrictive AN; 28 HC). We drew blood for OXT levels fasting and 60 min after a standard meal and performed T1-weighted MRI scans of the brain in the fasted state. MRI data was quality controlled and processed with FreeSurfer. Average gray matter brain volumes were extracted from the bilateral amygdala and hippocampus for each subject. Linear regression models were used to determine differences between AN and HC of postprandial percent change in OXT on amygdala and hippocampus gray matter volume. Results: Median [IQR] age was higher in females with AN (20.6 years [19.3, 21.5]) than HC (18.8 years [IQR 17.6, 20.3], p=0.02), and percentage of ideal body weight was lower in AN (75.5%) than HC (97.4%, p&lt;0.01). Right hippocampus volume, adjusted for age and total intracranial volume, was significantly lower in AN (estimated difference -188 dm3 [95%-CI -360, -17], p=0.04). Percent change in OXT was not different (p=0.5) but there was a trend for a positive interaction effect (p=0.08) for AN and percent change in OXT on right hippocampus volume. Posthoc exploratory analysis indicated a positive correlation in AN (R2=0.41, p=0.02) and no correlation in HC (R2=0.17,p=0.4) between percent change in OXT and right hippocampus volume. There was no significant between group difference in volume nor postprandial change in OXT for the bilateral amygdala or left hippocampus between groups. Discussion: Our results indicate smaller right hippocampus volume and a trend towards a positive association with postprandial change in OXT in AN compared to HC. Future studies will be important to better define the relationships between OXT secretion and food motivation brain regions and the impact on eating behavior in AN.

065 Sleep and Gray Matter Volume: The Role of Physiological Arousal

Introduction Insomnia is associated with increased arousal. Brain regions involved in chronic insomnia are diffuse and the potential interactive role of physiological arousal in the association between insomnia symptoms and neural regions is unknown. This study examined whether physiological arousal (heart rate variability, HRV) moderated the association between sleep and gray matter (GM) volume of frontal [dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC)] and temporal [right/left (R/L) hippocampus] regions in adults with comorbid chronic widespread pain and insomnia (CWPI). Methods Forty-seven adults with CWPI (Mage=46.00, SD=13.88, 89% women) completed two weeks of diaries measuring sleep onset latency (SOL), wake time after sleep onset (WASO) and total sleep time (TST). Resting HRV was assessed via Holter monitoring (5 minutes). Root mean squared standard deviation of successive normal-to-normal heartbeats (RMSDNN) was computed. T1-weighted magnetic resonance images were obtained, segmented and co-registered to MNI space. GM volumes (DLPFC, ACC, R/L hippocampus) were estimated (FSL). Multiple regressions examined whether SOL, WASO or TST were independently associated with or interacted with RMSDNN in their associations with GM volumes, controlling for age. Results SOL interacted with RMSDNN in its association with ACC (B=-4.60, SE=2.06, p=.03, R-squared=.06). Longer SOL was associated with lower ACC volume at highest RMSDNN (lowest arousal; B=-103.54, SE=42.82, p=.02), not average/lowest RMSDNN (highest arousal, ps&gt;.05). TST interacted with RMSDNN in its association with R hippocampus (B=-.22, SE=.10, p=.04, R-squared=.07). Shorter TST was associated with lower R hippocampal volume at lowest RMSDNN (highest arousal; B=7.39, SE=2.29, p=.002) and average RMSDNN (B=4.18, SE=1.50, p=.008), not highest RMSDNN (lowest arousal; p=.64). There was a trending association between WASO and R hippocampus volume (B=-13.67, SE=7.28, p=.07). Conclusion In patients with CWPI and highest physiological arousal, achieving longer TST may be important in terms of associations with right hippocampus volume. Improving (reducing) SOL may only impact ACC volume in those with lower physiological arousal. Trends of association between longer WASO and reduced right hippocampus volume warrant follow-up in larger samples. Findings highlight the interactive role of physiological arousal (HRV) in the neural mechanisms associated with sleep in CWPI. Support (if any) National Institute of Nursing Research (NR017168; Clinical trial: NCT02001077; PI: McCrae).

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases.Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups.Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode.Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.