Psychosocial factors and hippocampal subfields: The Medea-7T study.

Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to understand the role of psychosocial factors in the development of neurodegenerative diseases. A systematic review on psychosocial factors and hippocampal subfield volumes was performed and showed inconsistent results, highlighting the need for future studies to explore this relationship. The current study aimed to explore the association of psychosocial factors with hippocampal (subfield) volumes, using high-field 7T MRI. Data were from the Memory Depression and Aging (Medea)-7T study, which included 333 participants without dementia. Hippocampal subfields were automatically segmented from T2-weighted images using ASHS software. Generalized linear models accounting for correlated outcomes were used to assess the association between subfields (i.e., entorhinal cortex, subiculum, Cornu Ammonis [CA]1, CA2, CA3, dentate gyrus, and tail) and each psychosocial factor (i.e., depressive symptoms, anxiety symptoms, childhood maltreatment, recent stressful life events, and social support), adjusted for age, sex, and intracranial volume. Neither depression nor anxiety was associated with specific hippocampal (subfield) volumes. A trend for lower total hippocampal volume was found in those reporting childhood maltreatment, and a trend for higher total hippocampal volume was found in those who experienced a recent stressful life event. Among subfields, low social support was associated with lower volume in the CA3 (B = -0.43, 95% CI: -0.72; -0.15). This study suggests possible differential effects among hippocampal (subfield) volumes and psychosocial factors.

Intracranial Vessel Wall Lesions on 7T MRI (Magnetic Resonance Imaging).

Background and Purpose- Intracranial vessel wall lesions are a novel imaging marker of intracranial atherosclerosis (ICAS), but data on their occurrence and risk factors are lacking. Our aim was to study the frequency, distribution, and risk factors of intracranial vessel wall lesions on 7T magnetic resonance imaging in patients with a history of vascular disease. Methods- Within the SMART-MR study (Second Manifestations of Arterial Disease-Magnetic Resonance), cross-sectional analyses were performed in 130 patients (68±9 years) with assessable 7T intracranial vessel wall-magnetic resonance imaging data. Associations between vascular risk factors and ICAS burden, defined as the total number of vessel wall lesions, were estimated using linear regression analyses with ICAS burden as the dependent variable, adjusted for age and sex. Results- Ninety-six percent of patients had ≥1 vessel wall lesion. The mean±SD (range) ICAS burden was 8.5±5.7 (0-32) lesions. Significant associations were found between ICAS burden and age ( b=2.0 per +10 years; 95% CI, 0.81- 3.10), systolic blood pressure ( b=0.9 per +10 mm Hg; 95% CI, 0.27-1.42), diabetes mellitus ( b=3.2 for presence of diabetes mellitus; 95% CI, 0.79-5.72), hemoglobin A1c level ( b=1.2 per +1%; 95% CI, 0.19-2.26), apoB (apolipoprotein-B) ( b=4.7 per +1 g/L; 95% CI, 0.07-9.35), and hs-CRP (high-sensitivity C-reactive protein) level ( b=2.7 for hs-CRP >3 mg/L; 95% CI, 0.22-5.11). No significant associations were found with sex, smoking, and other lipid-factors. Conclusions- Vessel wall lesions are a novel and direct magnetic resonance imaging marker of ICAS. In this cohort, 96% of patients had at least 1 lesion on 7T vessel wall-magnetic resonance imaging. More lesions were found with older age, higher systolic blood pressure, diabetes mellitus, and higher levels of hemoglobin A1c, apoB, and hs-CRP.

Appendicitis Presenting As Cellulitis of the Right Leg.

BACKGROUND: Several infectious processes of intra-abdominal origin may atypically present as skin or soft tissue infections or abscess in the thigh. CASE REPORT: We describe the case of a 73-year-old woman who presented to the emergency department with the clinical picture of a skin infection of the right leg. The patient's condition deteriorated during medical treatment with intravenous antibiotics. Subsequent radiologic imaging revealed that the complaints were caused by a bulging retroperitoneal appendicular abscess along the iliopsoas muscle, although the patient experienced no abdominal symptoms. The patient recovered completely after surgical intervention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Timely performance of anatomic imaging in patients with unexplained skin or soft tissue infections and thigh abscesses is important because these findings may be manifestations of an abdominal pathology. A correct diagnosis in the emergency department prohibits delays in treatment.

The role of cognitive and brain reserve in memory decline and atrophy rate in mid and late-life: The SMART-MR study.

OBJECTIVE: Investigate associations of cognitive and brain reserve with trajectories of memory decline in mid-life and late-life, and whether the relationship of memory decline with atrophy differs as a function of reserve. METHODS: Participants were 989 Dutch middle-aged to older adults from the SMART-MR prospective cohort, followed up to 12 years with up to 3 measurements of memory and brain MRI. Education and Dutch National Adult Reading Test (DART) were used as proxies of cognitive reserve, and intracranial volume (ICV) and baseline brain parenchymal fraction (BPF) for brain reserve. Univariate growth curve models analyzed associations of reserve with memory decline, and multiple-group bivariate growth curve models tested the longitudinal brain-memory relationship as a function of reserve. Models were additionally stratified by mid-life and late-life. RESULTS: Higher DART, education, and BPF were related to a slower rate of memory decline, particularly in late-life, but ICV was not. A positive covariance indicated that an individual who undergoes atrophy also undergoes memory decline-this relationship did not differ across cognitive or brain reserve, but was not present in mid-life. Memory declined slower than brain volume, yet rates were more similar in the low DART, education, and BPF groups. DISCUSSION: Higher cognitive (DART, education) and brain reserve (BPF) work protectively in longitudinal memory change. ICV is an inappropriate proxy of brain reserve, failing to show any association with memory performance at baseline or over time. Deconstructing relationships of reserve capacities with longitudinal cognitive and brain outcomes may identify focus areas with potential for intervention.

White matter hyperintensity shape is associated with cognitive functioning - the SMART-MR study.

White matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function. In 563 patients with vascular disease (58 ± 10 years), we examined the relationship between WMH volume, shape, and cognitive functioning. WMH volume and shape were automatically determined on 1.5T brain MRI data. Standardized linear regression analyses estimated the association between WMH volume and shape (concavity index, solidity, convexity, fractal dimension, and eccentricity) and memory and executive functioning, adjusted for age, sex, educational level, and reading ability. Larger WMH volumes were associated with lower executive functioning Z-scores (b (95%-CI): -0.09 (-0.17;-0.01)). Increased shape complexity of periventricular/confluent WMH associated with lower executive functioning (concavity index +1SD: -0.13 (-0.20;-0.06); solidity -1SD: -0.09 (-0.17;-0.02)) and lower memory function (fractal dimension +1SD: -0.10 (-0.18;-0.02)). Of note, the association between concavity index and executive functioning was independent of WMH volume (-0.12 (-0.19;-0.04)). Our results suggest that WMH shape contains additional information about WMH burden, not otherwise captured by WMH volume.

Intracranial atherosclerosis on 7T MRI and cognitive functioning: The SMART-MR study.

OBJECTIVE: To investigate the association between intracranial atherosclerosis (ICAS) and cognitive functioning in patients with a history of vascular disease. METHODS: Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed in 130 patients (mean ± SD age 68 ± 9 years) with 7T vessel wall MRI data. Vessel wall lesions were rated according to established criteria and summed into a circulatory and artery-specific ICAS burden. Associations between ICAS burden and Z scores of memory, executive functioning, working memory, and processing speed were estimated using linear regression analyses adjusted for age, sex, education, reading ability, and vascular risk factors. RESULTS: A total of 125 patients (96%) had ≥1 vessel wall lesion; the mean ICAS burden was 8.5 ± 5.7. A statistically nonsignificant association was found between total ICAS burden and memory (b = -0.03 per +1 lesion; 95% confidence interval [CI] -0.05 to 0.00). No associations were found for the other domains. A statistically significant association was found for ICAS burden of the posterior cerebral artery (PCA) and memory (b = -0.12 per +1 lesion; 95% CI -0.23 to -0.01) and executive functioning (b = -0.10 per +1 lesion; 95% CI -0.19 to -0.01). Statistically nonsignificant associations were found for the anterior cerebral artery (ACA) burden and memory (b = -0.13 per +1 lesion; 95% CI -0.26 to 0.01) and executive functioning (b = -0.11 per +1 lesion; 95% CI -0.22 to 0.01). Additional adjustments for large infarcts, white matter hyperintensities, lacunes, and ≥50% carotid stenosis produced similar results. CONCLUSIONS: Our results suggest an artery-specific vulnerability of memory and executive functioning to ICAS, possibly due to strategic brain regions involved with these cognitive domains, which are located in the arterial territory of the PCA and ACA.

Vascular Risk Factors of Hippocampal Subfield Volumes in Persons without Dementia: The Medea 7T Study.

BACKGROUND: Vascular risk factors have been associated with risk of Alzheimer's disease (AD) and volume loss of the hippocampus, but the associations with subfields of the hippocampus are understudied. Knowing if vascular risk factors contribute to hippocampal subfield atrophy may improve our understanding of vascular contributions to neurodegenerative diseases. OBJECTIVE: To investigate the associations between age, sex, and vascular risk factors with hippocampal subfields volumes on 7T MRI in older persons without dementia. METHODS: From the Medea 7T study, 283 participants (67±9 years, 68% men) without dementia had 7T brain MRI and hippocampal subfield segmentation. Subfields were automatically segmented on the 3D T2-weighted 7T images with ASHS software. Using linear mixed models, we estimated adjusted associations of age, sex, and vascular risk factors with z-scores of volumes of the entorhinal cortex (ERC), subiculum (SUB), Cornu Ammonis (CA)1, CA2, CA3, CA4, and dentate gyrus (DG), and tail as multivariate correlated outcomes. RESULTS: Increasing age was associated with smaller volumes in all subfields, except CA4/DG. Current smoking was associated with smaller ERC and SUB volumes; moderate alcohol use with smaller CA1 and CA4/DG, obesity with smaller volumes of ERC, SUB, CA2, CA3, and tail; and diabetes mellitus with smaller SUB volume. Sex, former smoking, and hypertension were not associated with subfield volumes. When formally tested, no risk factor affected the subfield volumes differentially. CONCLUSION: Several vascular risk factors were associated with smaller volumes of specific hippocampal subfields. However, no statistical evidence was found that subfields were differentially affected by these risk factors.

Hippocampal sulcal cavities: prevalence, risk factors and association with cognitive performance. The SMART-Medea study and PREDICT-MR study.

Hippocampal sulcal cavities (HSCs) are frequently observed on MRI, but their etiology and relevance is unclear. HSCs may be anatomical variations, or result from pathology. We assessed the presence of HSCs, and their cross-sectional association with demographics, vascular risk factors and cognitive functioning in two study samples. Within a random sample of 92 patients with vascular disease from the SMART-Medea study (mean age = 62, SD = 9 years) and 83 primary care patients from the PREDICT-MR study (mean age = 62, SD = 12 years) one rater manually scored HSCs at 1.5 T 3D T1-weighted coronal images blind to patient information. We estimated relative risks of age, sex and vascular risk factors with presence of HSCs using Poisson regression with log-link function and robust standard errors adjusted for age and sex. Using ANCOVA adjusted for age, sex, and education we estimated the association of the number of HSCs with memory, executive functioning, speed, and working memory. In the SMART-Medea study HSCs were present in 65% and in 52% in the PREDICT-MR study (χ2 = 2.99, df = 1, p = 0.08). In both samples, no significant associations were observed between presence of HSCs and age (SMART-Medea: RR = 1.00; 95%CI 0.98-1.01; PREDICT-MR: RR = 1.01; 95%CI 0.99-1.03), sex, or vascular risk factors. Also, no associations between HSCs and cognitive functioning were found in either sample. HSCs are frequently observed on 1.5 T MRI. Our findings suggest that, in patients with a history of vascular disease and primary care attendees, HSCs are part of normal anatomic variation of the human hippocampus rather than markers of pathology.

Subjective cognitive decline, brain imaging biomarkers, and cognitive functioning in patients with a history of vascular disease: the SMART-Medea study.

We estimated associations of subjective cognitive decline (SCD) with neuroimaging markers of dementia and cognitive functioning in patients with a history of vascular disease without objective cognitive impairment. Within the Second Manifestations of ARTerial disease-Memory, depression and aging study, 599 patients (62 ± 9 years) had 1.5 T brain magnetic resonance imaging and cognitive testing at the baseline and after 8 years of follow-up. Using multiple regression analyses, we estimated cross-sectional and longitudinal associations of SCD according to research criteria with volumes of total brain, hippocampus, white matter hyperintensities, and presence of lacunes and with memory, executive functioning, information processing speed, and working memory. SCD was associated with increased risk of lacunes at the baseline (relative risk = 1.48, 95% confidence interval: 1.03; 2.12) but not during follow-up. No significant associations with volumes of white matter hyperintensities, total brain, or hippocampus were observed. SCD was cross-sectionally associated with poorer executive functioning and speed but not during follow-up. More prospective studies are needed to further elucidate the relationship between SCD, brain imaging markers, and cognitive decline and the role of SCD in the preclinical stage of Alzheimer's disease.