Total Hippocampal Volume Research Articles

Influence of lung function on macro- and micro-structural brain changes in mid- and late-life.

Lung function has been associated with cognitive decline and dementia, but the extent to which lung function impacts brain structural changes remains unclear. We aimed to investigate the association of lung function with structural macro- and micro-brain changes across mid- and late-life. The study included a total of 37164 neurologic disorder-free participants aged 40-70years from the UK Biobank, who underwent brain MRI scans 9years after baseline. After 2.5years, a subsample (n=3895) underwent a second MRI scan. Lung function was assessed using a composite score based on forced expiratory volume in 1 second, forced vital capacity, and peak expiratory flow, and divided into tertiles (i.e., low, moderate, and high). Structural brain volumes (including total brain, gray matter, white matter, hippocampus, and white matter hyperintensities) and diffusion markers (fractional anisotropy [FA] and mean diffusivity [MD]) were assessed. Data were analyzed using linear regression and mixed-effects models. Compared to high lung function, low lung function was associated with smaller total brain, gray matter, white matter, and hippocampal volume, as well as lower white matter integrity. Over the 2.5-year follow-up, low lung function was associated with reduced white matter and hippocampal volume, reduced FA, and increased white matter hyperintensity volume and MD. After stratification by age, the associations remained significant among adults aged 40-60years and 60+years. Low lung function is associated with macro- and micro-structural brain changes involving both neurodegenerative and vascular pathologies. This association is significant in both mid- and late-life.

Walking and Hippocampal Formation Volume Changes: A Systematic Review.

Sustaining the human brain's hippocampus from atrophy throughout ageing is critical. Exercise is proven to be effective in promoting adaptive hippocampal plasticity, and the hippocampus has a bidirectional relationship with the physical environment. Therefore, this systematic review explores the effects of walking, a simple physical activity in the environment, on hippocampal formation volume changes for lifelong brain and cognitive health. PubMed, Scopus, and Web of Science were searched for studies on humans published up to November 2022 examining hippocampal volume changes and walking. Twelve studies met the inclusion criteria. Study quality was assessed using the PEDro scale and ROBINS-I tool. A narrative synthesis explored walking factors associated with total, subregional, and hemisphere-specific hippocampal volume changes. Overall, walking had positive effects on hippocampal volumes. Several studies found benefits of higher-intensity and greater amounts of walking for total hippocampal volume. The subiculum increased after low-intensity walking and nature exposure, while the parahippocampal gyrus benefited from vigorous intensity. The right hippocampus increased with spatial navigation during walking. No studies examined the effect of walking on the dentate gyrus. This systematic review highlights walking as a multifaceted variable that can lead to manifold adaptive hippocampal volume changes. These findings support the promotion of walking as a simple, effective strategy to enhance brain health and prevent cognitive decline, suggesting the design of physical environments with natural and biophilic characteristics and layouts with greater walkability and cognitive stimulation. Future research is encouraged to explore the hippocampal subregional changes instead of focusing on total hippocampal volume, since the hippocampal formation is multicompartmental and subfields respond differently to different walking-related variables.

Life's Essential 8 and midlife trajectories in cognition and brain health: The CARDIA study.

Poor cardiovascular health (CVH) is linked to Alzheimer's disease and dementia; however, its association with neurocognitive trajectories earlier in life remains underexplored. We included 3224 participants with information on CVH at early midlife (mean age 45.0±standard deviation 3.4) an cognitive assessments, and neuroimaging 5, 10, and 15 years later including white matter hyperintensities (WMHs), total gray matter (GM), and hippocampal volume. CVH was operationalized according to the American Heart Association's (AHA) "Life's Essential 8" (LE8) guidelines. The association between LE8 and cognitive and neuroimaging measures was examined using mixed linear regression adjusting for age, sex, race, and education. Worse LE8 score was associated with steeper decline in cognition, higher accumulation of WMHs, and steeper decline in total GM and hippocampal volume. Poor CVH is related to accelerated brain aging across midlife, highlighting the need to screen for and improve CVH earlier to prevent adverse cognitive outcomes. Poor cardiovascular health in early midlife is associated with faster decline in cognition across 10 years overall and in specific domains. Poor and intermediate cardiovascular health was associated with higher accumulation of white matter hyperintensities across midlife. Poor cardiovascular health was associated with faster atrophy in total gray matter volume and hippocampal volume.

Serotonin enhances neurogenesis biomarkers, hippocampal volumes, and cognitive functions in Alzheimer’s disease

Research on serotonin reveals a lack of consensus regarding its role in brain volume, especially concerning biomarkers linked to neurogenesis and neuroplasticity, such as ciliary neurotrophic factor (CNTF), fibroblast growth factor 4 (FGF-4), bone morphogenetic protein 6 (BMP-6), and matrix metalloproteinase-1 (MMP-1) in Alzheimer’s disease (AD). This study aimed to investigate the influence of serotonin on brain structure and hippocampal volumes in relation to cognitive functions in AD, as well as its link with biomarkers like CNTF, FGF-4, BMP-6, and MMP-1. Data from 133 ADNI participants with AD included cognitive assessments (CDR-SB), serotonin measurements (Biocrates AbsoluteIDQ p180 kit, UPLC-MS/MS), and neurotrophic factors quantified via multiplex proteomics. Gray matter volume changes were analyzed using Voxel-Based Morphometry (VBM) with MRI. Statistical analyses employed Pearson correlation, bootstrap methods, and FDR-adjusted p-values (< 0.05 or < 0.01) via the Benjamini–Hochberg procedure, alongside nonparametric methods. The analysis found a positive correlation between serotonin levels and total brain (r = 0.229, p = 0.023) and hippocampal volumes (right: r = 0.186, p = 0.032; left: r = 0.210, p = 0.023), even after FDR adjustment. Higher serotonin levels were linked to better cognitive function (negative correlation with CDR-SB, r = −0.230, p = 0.024). Notably, serotonin levels were positively correlated with BMP-6 (r = 0.173, p = 0.047), CNTF (r = 0.216, p = 0.013), FGF-4 (r = 0.176, p = 0.043), and MMP-1 (r = 0.202, p = 0.019), suggesting a link between serotonin and neurogenesis and neuroplasticity. However, after adjusting for multiple comparisons and controlling for confounding factors such as age, gender, education, and APOE genotypes (APOE3 and APOE4), none of the correlations of biomarkers remained statistically significant. In conclusion, increased serotonin levels are associated with improved cognitive function and increased brain volume. However, associations with CNTF, FGF-4, BMP-6, and MMP-1 were not statistically significant after adjustments, highlighting the complexity of serotonin’s role in AD and the need for further research.Graphical

Subjective Social Status, Brain Health, and Cognitive Reserve Across Race/Ethnicity and Sex/Gender

AbstractBackgroundSubjective social status in the US (SSS) is related to physical, mental, and cognitive health independent of socioeconomic status, yet few studies have assessed SSS in one’s community or examined how SSS may function differentially across the intersection of race and gender. This study aimed to assess the relationships between SSS‐US, SSS‐community, brain health, and cognitive reserve utilizing an intersectional lens to extend the literature on social determinants of Alzheimer’s disease and related dementia (ADRD) risk.MethodsParticipants were 867 older adults from the Washington Heights‐Inwood Columbia Aging Project (WHICAP). SSS relative to the US and one’s community were based on the MacArthur Scale of SSS. Brain health was operationalized as total volume of white matter hyperintensities (WMH), total gray matter volume, total hippocampal volume, and mean cortical thickness across nine AD signature regions. Cognitive reserve was operationalized as residual variance in an episodic memory composite after accounting for all brain health measures. Separate multiple linear regressions assessed unique relationships between the two SSS predictors and the brain health and cognitive reserve outcomes while adjusting for sociodemographics. Multiplicative interaction terms examined whether associations involving SSS were moderated by sex/gender, race/ethnicity, and their intersection.ResultsThere were no relationships between SSS‐community or SSS‐US and brain health across the full sample. Among White women, higher SSS‐community was associated with lower WMH (B = ‐0.33, p = 0.047). Among Black men, higher SSS‐community was associated with lower hippocampal volume (B = ‐0.31, p = 0.04). In sensitivity analyses, higher SSS‐community was associated with lower hippocampal volume among older (B = ‐0.30, p = 0.048), but not younger (B = ‐0.21, p = 0.37) Black men. Neither SSS‐US nor SSS‐community was associated with cognitive reserve.ConclusionsThis study highlights the value of assessing community standing in addition to US standing to understand social determinants of ADRD risk, as community standing may be more predictive of brain health. From an intersectional lens, community standing may be most strongly related to cerebrovascular health among White women, who appeared more sensitive to both low and high community standing. Counterintuitive findings among Black men likely reflect selective survival. Further research should explore longitudinal relationships between community standing and brain health.

Higher MIND diet scores are associated with larger brain MRI hippocampal volume: the cross‐cohort collaboration

AbstractBackgroundHigher Mediterranean‐ DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community‐based cohort. We investigated cross‐sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community‐based cohorts.MethodWe analyzed data from 3130 dementia‐, stroke‐ and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort. Individuals completed a brain magnetic resonance imaging (MRI) scan, and a validated food frequency questionnaire (FFQ) (ARIC, CHS, FOS, RS), 24h dietary recall (3C), or an extensive food list (SHIP). The MIND diet consists of ten healthy (e.g. green leafy vegetables, berries and fish) and five unhealthy (e.g. cheese, red meat and products and fast fried foods) components. Outcomes from brain MRI included TBV, total grey matter volume (TGMV), hippocampal volume (HPV), and WMHV. We used multivariable linear regression to relate MIND diet adherence to the outcomes. Results were combined in meta‐analysis using fixed effects and random effects models.ResultHigher MIND diet scores (score range: 0‐15) were associated with larger HPV (beta = 0.015, 95% confidence interval = 0.004 to 0.026, cm³ per one unit MIND diet score increase) after adjustment for age, age squared, sex, time from clinical exam to brain MRI exam, total intracranial volume and energy intake, but not with TBV, TGMV and WMHV. Heterogeneity between studies was low (I2 = 0% TBV, TGMV, HPV) to moderate (I2 = 44% WMHV).ConclusionIn cross‐sectional analyses, higher MIND diet scores were associated with larger HPV, but not with other brain volume measures. It might be that HPV was a more sensitive marker of brain health in the populations under study. Future studies are encouraged to examine the associations between the MIND diet and amyloid and tau positron emission tomography (PET) imaging to elucidate whether a relationship between the MIND diet and dementia pathologies exists.

Association between hemoglobin levels and cerebral white matter volume in a general older Japanese population: the Iki-Iki study.

Although previous studies have reported that hemoglobin levels can affect the brain, very few have focused on the association between hemoglobin levels and brain volume. We aimed to identify the influence of hemoglobin levels on brain volume measured using magnetic resonance imaging (MRI) in a large elderly population. This cross-sectional study included 2153 participants (median age, 69 years; 60.2% female) who underwent 3T brain MRI. Multiple regression analyses were performed after adjusting for potential confounders. In the subgroup analyses, participants were divided into four groups according to sex and age threshold (lower age group [65-74] and higher age group [≥ 75]). After adjusting for potential confounders, total white matter volume reduction was found to be associated with decreased hemoglobin levels (females: standardized β = 0.059, [95% confidence interval (CI): 0.0032, 0.11], P = 0.038, males: standardized β = 0.069 [95% CI: -0.00023, 0.14], P = 0.051). This relationship was notable in younger age groups of both sexes. After adjustment, the total gray matter and hippocampal volumes were not significantly associated with hemoglobin levels. Low hemoglobin levels may have deleterious effects on white matter volume, which diminishes with age.

Effects of aerobic exercise on hippocampal formation volume in people with schizophrenia – a systematic review and meta-analysis with original data from a randomized-controlled trial

Abstract Background The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications. Methods The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes. Results Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus. Conclusions Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.

Neuroinflammation modifies the relationship between stress and perivascular spaces in an elderly population with different levels of cognitive impairment.

Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer's disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment. Using brain MRI scans acquired at 1.5 T, PVS were quantified in a cohort of 461 individuals, consisting of cognitively healthy controls (n = 48), people with mild cognitive impairment (MCI, n = 322) and Alzheimer's disease (AD, n = 91). PVS volume fraction was calculated in the basal ganglia and centrum semiovale using a semi-automated segmentation approach. Stress was quantified with levels of salivary cortisol. Inflammatory biomarkers measured from plasma included cytokines, matrix metalloproteinases and C-reactive protein. General linear models were used to test the relationship between PVS and cortisol, when interacting with inflammatory markers. This was done on the whole cohort and within each clinical cognitive group. In the centrum semiovale, higher inflammation levels reduced the relationship of cortisol with PVS. In basal ganglia, higher levels of C-reactive protein reduced the negative relationship of cortisol with PVS. All analyses were accounted for age, sex, body mass index (BMI) and total hippocampal volume. There was a significant interaction effect between cortisol and C-reactive protein on PVS volume fraction in the MCI group. These findings suggest an influence of neuroinflammation on the PVS structure in Alzheimer's disease spectrum, and offer insight for better understanding physiological processes of cognitive impairment onset.

Do total hippocampus and hippocampal subfield volumes relate to navigation ability? A call towards methodological consistency

Despite the need for successful navigation, humans vary greatly in their ability to navigate, and these individual differences may relate to variation in brain structure. While prior research provides support for a correlation between hippocampal volume and navigation ability in both navigation experts and in older individuals, this relationship is under scrutiny for healthy, young adults. We assessed 99 healthy young adults' ability to navigate in a virtual, desktop maze and correlated their performance with total hippocampal gray matter volume. For a subset of these individuals, we further segmented the medial temporal lobe—including regions of the hippocampus—into anatomically-distinct subregions to uniquely examine the association between volumes of hippocampal subfields and navigation. Given the need to distinguish between similar-looking maze hallways and partially overlapping routes, young adults with stronger pattern separation ability may perform better in this task. Thus, we theorized that successful navigation would positively correlate with hippocampal CA3 and dentate gyrus (DG) subfield volumes due to these regions' role in pattern separation. CA1 and entorhinal cortex (ERC) are both associated with rodent spatial memory, too, suggesting a possible relationship between their volumes and navigation performance. Consistent with our hypotheses, we observed a positive relationship between volumes of hippocampal subfields and wayfinding accuracy, while ERC and parahippocampal cortex volumes correlated with navigation efficiency. However, when analyzing total hippocampal volume, a nuanced interpretation is warranted. We found evidence of Simpson's Paradox, where total hippocampal volume and navigation accuracy displayed no correlation in males, a negative correlation in females, yet a positive correlation when considering the full sample of males and females combined. Furthermore, no significant relationship was observed between total hippocampal volume and path efficiency. Given these findings, we urge caution in interpreting the results because these associations differ by analysis techniques (including voxel-based morphometry), after sex stratification, and with anterior and posterior hippocampal subdivisions. Overall, this study enhances our understanding of the relationship between brain volume and navigation ability for young adults but also emphasizes the need for methodological consistency across studies with respect to boundary definitions, neuroimaging techniques, statistical methods, and factors that give rise to individual differences.

Association of lamina cribrosa thickness and hippocampal volume in Alzheimer's disease patients.

Alzheimer's disease (AD) is the most common cause of dementia and affects a large portion of the elderly population worldwide. To analyze the relationship between lamina cribrosa thickness (LCT) and hippocampal volume in patients with AD and mild cognitive impairment (MCI). The sample in the present study consisted of 20 recently diagnosed MCI patients, 20 recently diagnosed AD patients, and 20 matched healthy volunteers. Every patient underwent magnetic resonance imaging (MRI) scans. The VolBrain software (open-access platform for MRI brain analysis) was used to calculate the hippocampal volume. Optical coherence tomography was performed to measure the LCT. Analysis of variance and Pearson chi-squared tests were employed to assess the results. The lowest total hippocampal volume (p < 0.05) was in the AD group, which was 6.14 ± 0.66 mm3, while in the control group, it was 7.7 ± 9.65 mm3, and 6.69 ± 0.46 mm3 in the MCI group. In comparison to the rest of the groups, in the AD group, the LCT was the thinnest (202.17 ± 16.35 µm). As per the results of the study population as a whole, low hippocampal volume causes low LCT, which shows an important relationship (r: 0.41; p < 0.05). The current findings present evidence of the relationship between hippocampal volume and LCT in patients with AD and MCI.

It Takes Three: Parental Hostility, Brain Morphology, and Child Externalizing Problems in a Parent-Offspring Neuroimaging Trio Design.

Hostility often co-occurs in parents and associates with increased aggression and inattention problems in children. In this population-based cohort of 484 mother-father-child neuroimaging trios, we investigated the degree to which associations of prenatal and childhood parental hostility would be associated with maternal, paternal, and child brain structural differences. Also, we examined whether hippocampal volumes of the parents or child mediate the association of prenatal parental hostility with child externalizing behaviors. Maternal and paternal hostility was assessed with the hostility subscale of the Brief Symptom Inventory at three time points: prenatally at 30 weeks' gestation and when the child was 3 and 10 years old. During adolescence assessment wave (age 14), maternal, paternal, and offspring assessment included a magnetic resonance imaging. Child externalizing problems were assessed with Youth Self-Report Child Behavior Checklist. Our findings suggest that maternal and paternal hostility were each associated with smaller gray matter, white matter, and hippocampal volumes of their own and their partner's brain. Prenatal maternal but not paternal hostility was associated with smaller total gray matter, white matter, and hippocampal volumes in the offspring. The child's hippocampal volumes partially mediated the associations of prenatal parental hostility (latent construct) with adolescent externalizing behavior, even after adjusting for prior child externalizing problems. Moreover, parental psychopathology may have long-lasting neurodevelopmental correlates in children that underlie the intergenerational transmission of behavioral problems. The behavior of family members results from a system of interdependent dyadic relationships over time that associate with specific brain structural differences.

Sex differences in association between dietary sodium intake and white matter hyperintensity volume

Abstract Background There is limited evidence on the relationship between dietary sodium intake (dNa) and brain health, and very little on sex differences in associations. Purpose To study the relationship between dNa and imaging measures of brain health in men and women from the INSIGHT 46 substudy of the MRC National Survey of Health and Development (British 1946 birth cohort). Methods Participants had measurements (dNa using 5-day food diary, anthropometrics, blood pressure (BP) body mass index (BMI)) at 60-64years. Whole-brain and hippocampal volumes, white matter hyperintensity volume (WMHV) and florbetapir amyloid-β positivity were measured using MRI-PET imaging at 69-71years. Associations (β (95% confidence intervals)) were estimated separately in men and women using generalized linear models with robust standard errors adjusted for potential confounders (age, diet quality, energy intake, socioeconomic status) or potential mediators (BMI, BP). Results Participants’ characteristics are shown in Table 1. In women but not men dNa was positively associated with higher WMHV (β[women]=32(1, 72) %/g; p=0.043; β[men]=-10(-27, 11)%/g; p=0.342); this relationship in women was independent of BMI (β = 32(1, 72)%/g; p = 0.043) or systolic BP (β = 31(1, 70)%/g; p=0.041). dNa was not associated with total brain volume, hippocampal volume or amyloid-β positivity in either sex. Conclusions Elevated sodium consumption in the diet is associated with cerebral small vessel disease in older age women but not men. This association was independent of BMI or BP.Table 1

Hippocampal volumes in UK Biobank are associated with APOE only in older adults.

The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and apolipoprotein E (APOE) genotype on total hippocampal volume. Using neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and APOE with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling. Total hippocampal volume declined with age, with significant differences by APOE genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at the age of 76. The association of APOE and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of APOE genotype in determining when to begin screening for AD. Apolipoprotein E (APOE) genotype shows an age-dependent association with total hippocampal volume.No association between APOE and total hippocampal volume was detected before age 60.Accelerated decline was observed in ε4/ε4 carriers at age 61 and ε3/ε4 at age 69.Delayed decline was evident in ε2/ε3 carriers starting at age 76.

Interactions between muscle volume and body mass index on brain structure in the UK Biobank.

Low skeletal muscle volume may increase dementia risk through mechanisms affecting brain structure. However, it is unclear whether this relationship exists outside of sarcopenia and/or varies by other factors. We aimed to study the interplay between skeletal muscle volume and factors, such as age, sex, and body mass index (BMI), in explaining brain structure at midlife in a cohort without sarcopenia. We used abdominal and brain magnetic resonance imaging (MRI) data from a population-based cohort enrolled in the UK Biobank. The following measures were derived: thigh fat-free muscle volume (FFMV), total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), total hippocampal volume (THV), and white matter hyperintensity volume (WMHV). Participants below sex-based grip strength thresholds suggesting probable sarcopenia were excluded. Linear regression analysis was used to study the interaction or mediation effects of age, sex, and BMI on the associations between FFMV and brain volumes. Data were available for 20,353 participants (median age 64 years, 53% female). We found interactions between thigh FFMV, BMI, and age (all p < 0.05). Greater thigh FFMV was associated with better brain volumes in those aged <64 years with normal (TBV: β = 2.0 ml/L, p = 0.004; GMV: β = 0.8 ml/L, p = 0.04; WMV: β = 1.1 ml/L, p = 0.006; WMHV: β = -0.2 ml/L, p = 3.7 × 10-5) or low BMI (TBV: β = 21.2 ml/L, p = 0.003; WMV: β = 13.3 ml/L, p = 0.002, WMHV: β = -1.1 ml/L, p = 0.04). Greater thigh muscle volume correlates with better brain volumes at midlife in people without sarcopenia, but this relationship weakens with greater age and BMI. Further study is required to investigate the underlying mechanisms to understand which components of body composition are potentially modifiable risk factors for dementia.

Effects of glycaemic control on memory performance, hippocampal volumes and depressive symptomology

BackgroundDiabetes and poor glycaemic control have been shown to negatively impact cognitive abilities, while also raising risk of both mood disorders and brain structural atrophy. Sites of atrophy include the hippocampus, which has been implicated in both memory performance and depression. The current study set out to better characterise the associations between poor glycaemic control, memory performance, and depression symptoms, and investigate whether loss of hippocampal volume could represent a neuropathological mechanism underlying these.Methods1331 participants (60.9% female, age range 18–88 (Mean = 44.02), 6.5% with likely diabetes) provided HbA1c data (as an index of glycaemic control), completed a word list learning task, and a validated depression scale. A subsample of 392 participants underwent structural MRI; hippocampal volumes were extracted using FreeSurfer.ResultsPartial correlation analyses (controlling for age, gender, and education) showed that, in the full sample, poorer glycaemic control was related to lower word list memory performance. In the MRI sub-sample, poorer glycaemic control was related to higher depressive symptoms, and lower hippocampal volumes. Total hippocampus volume partially mediated the association between HbA1c levels and depressive symptoms.ConclusionsResults emphasise the impact of glycaemic control on memory, depression and hippocampal volume and suggest hippocampal volume loss could be a pathophysiological mechanism underlying the link between HbA1c and depression risk; inflammatory and stress-hormone related processes might have a role in this.

Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia.

Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia. From the Amsterdam Dementia Cohort, we selected amyloid-positive participants with MCI or mild dementia and at least 2 longitudinal Mini-Mental State Examination (MMSE) measurements. Amyloid positivity was based on CSF AD biomarker concentrations or amyloid PET. We used linear mixed modeling to predict MMSE over time, describing trajectories using a cubic time curve and interactions between linear time and the baseline predictors age, sex, baseline MMSE, APOE ε4 dose, CSF β-amyloid (Aβ) 1-42 and pTau, and MRI total brain and hippocampal volume. Backward selection was used to reduce model complexity. These models can predict MMSE over follow-up or the time to an MMSE value. MCI and mild dementia were modeled separately. Internal 5-fold cross-validation was performed to calculate the explained variance (R2). In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years. Cognitive decline rates increased over time for both MCI and mild dementia (model comparisons linear vs squared vs cubic time fit; p < 0.05 favoring a cubic fit). For MCI, backward selection retained age, sex, and CSF Aβ1-42 and pTau concentrations as time-varying effects altering the MMSE trajectory. For mild dementia, retained time-varying effects were Aβ1-42, age, APOE ε4, and baseline MMSE. R2 was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aβ1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%. We constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and the remaining uncertainty and aid in conversations about individualized potential treatment effects.

Hippocampus and olfactory impairment in Parkinson disease: a comparative exploratory combined volumetric/functional MRI study.

Patients with Parkinson's Disease (PD) commonly experience Olfactory Dysfunction (OD). Our exploratory study examined hippocampal volumetric and resting-state functional magnetic resonance imaging (rs-fMRI) variations in a Healthy Control (HC) group versus a cognitively normal PD group, further categorized into PD with No/Mild Hyposmia (PD-N/MH) and PD with Severe Hyposmia (PD-SH). We calculated participants' relative Total Hippocampal Volume (rTHV) and performed Spearman's partial correlations, controlled for age and gender, to examine the correlation between rTHV and olfactory performance assessed by the Odor Stick Identification Test for the Japanese (OSIT-J) score. Mann-Whitney U tests assessed rTHV differences across groups and subgroups, rejecting the null hypothesis for p < 0.05. Furthermore, a seed-based rs-fMRI analysis compared hippocampal connectivity differences using a one-way ANCOVA covariate model with controls for age and gender. Spearman's partial correlations indicated a moderate positive correlation between rTHV and OSIT-J in the whole study population (ρ = 0.406; p = 0.007), PD group (ρ = 0.493; p = 0.008), and PD-N/MH subgroup (ρ = 0.617; p = 0.025). Mann-Whitney U tests demonstrated lower rTHV in PD-SH subgroup compared to both HC group (p = 0.013) and PD-N/MH subgroup (p = 0.029). Seed-to-voxel rsfMRI analysis revealed reduced hippocampal connectivity in PD-SH subjects compared to HC subjects with a single cluster of voxels. Although the design of the study do not allow to make firm conclusions, it is reasonable to speculate that the progressive involvement of the hippocampus in PD patients is associated with the progression of OD.

Exploring the cognitive assessment potential of MRI-based volumetric hippocampal segmentation in Parkinson's disease.

To investigate the potential of magnetic resonance imaging (MRI)-based total and segmental hippocampus volume analysis in the assessment of cognitive status in Parkinson's disease (PD). We divided participants into three groups Group A-Parkinson patients (Pp) with normal cognitive status (n=25), Group B-Pp with dementia (n=17), and Group C-healthy controls (n=37). Three-dimensional T1W Fast Spoiled Gradient Recalled Echo images were used for Volbrain hippocampus subfield segmentation. We used the "Winterburn" protocol, which divides the hippocampus into five segments, Cornu Ammonis (CA),CA2/CA3, CA4/dentate gyrus, stratum radiatum, lacunosum, and moleculare, and subiculum. A total of 79 participants were included in the study, consisting of 42 individuals with PD (64.2% male) and 37 healthy controls (54.1% male). The mean age of PD was 60.9±10.7 years and the mean age of control group was 59.27±12.3 years. Significant differences were found in total hippocampal volumes between Group A and B (p=.047. Statistically significant group differences were found in total, right, and left CA1 volumes (analysis of variance [ANOVA]: F(2,76)=8.098, p=.001; F(2,76)=7.628, p=.001; F(2,76)=5.084, p=.008, respectively), as well as in total subiculum volumes (ANOVA: F(2,76)=4.368, p=.016). Post hoc tests showed that total subiculum volume was significantly lower in individuals with normal cognitive status (0.474±0.116cm3) compared to healthy controls (0.578±0.151cm3, p=.013). Volumetric hippocampal MRI can be used to assess the cognitive status of Pp. Longitudinal studies that evaluate Pp who progress from normal cognition to dementia are required to establish a causal relationship.

Childhood blood-lead level predicts lower general, non-selective hippocampal subfield volumes in midlife

Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer’s disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972–1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm3 per 5 ug/dL-unit greater blood-lead level, 95 %CI: −175.4 to −29.7, p=.006, β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (pFDR<.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation.