Temporal Lobe Volume Research Articles

Brain-behavior investigation of potential cognitive markers of Alzheimer's disease in middle age: a multi-modal imaging study.

Early detection of Alzheimer's disease remains a challenge, and the development and validation of novel cognitive markers of Alzheimer's disease is critical to earlier disease detection. The goal of the present study is to examine brain-behavior relationships of translational cognitive paradigms dependent on the medial temporal lobes and prefrontal cortices, regions that are first to undergo Alzheimer's-associated changes. We employed multi-modal structural and functional MRI to examine brain-behavior relationships in a healthy, middle-aged sample (N = 133; 40-60years). Participants completed two medial temporal lobe-dependent tasks (virtual Morris Water Task and Transverse Patterning Discriminations Task), and a prefrontal cortex-dependent task (Reversal Learning Task). No associations were found between various MRI measures of brain integrity and the Transverse Patterning or Reversal Learning tasks (p's > .05). We report associations between virtual Morris Water Task performance and medial temporal lobe volume, hippocampal microstructural organization, fornix integrity, and functional connectivity within the executive control and frontoparietal control resting state networks (all p's <0.05; did not survive correction for multiple comparisons). This study suggests that virtual Morris Water Task performance is associated with medial temporal lobe integrity in middle age, a critical window for detection and prevention of Alzheimer's disease, and may be useful as an early cognitive marker of Alzheimer's disease risk.

Influence of MRI on Diagnostic Efficacy and Satisfaction of Patients with Alzheimer's Disease.

Objective To inquire into the influence of magnetic resonance imaging (MRI) on the diagnostic efficacy and satisfaction of patients with Alzheimer's disease (AD). Methods This study included 42 healthy people (control group) and 66 patients with AD (AD group). The hippocampus volume, temporal sulcus spacing, left-right brain diameter, brain lobe volume, hippocampal height, temporal horn width, lateral fissure width, and degree of leukoaraiosis were all measured using an MRI scan. After diagnosis, the satisfaction of patients in both arms was investigated and the satisfaction degree was recorded. Results Compared with the control group, the left and right hippocampal volumes and hippocampal height of AD patients were smaller, while the temporal sulcus spacing, temporal horn width, lateral fissure width, and left-right brain diameter were remarkably higher. A statistical difference was present in the degree of leukoaraiosis between the two arms. The frontal and temporal lobe volumes of AD patients were notably lower while the volumes of parietal and occipital lobes were similar, versus the control group. The total satisfaction was 83.33% in the control group and 86.36% in the AD group, with no statistical difference between the two arms. Conclusions MRI can effectively mine the brain information of AD patients with a high patient satisfaction, which has potential value in clinical application.

The relationship between plasma free fatty acids, cognitive function and structural integrity of the brain in middle-aged healthy humans

Background: The cerebral composition of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) is believed to influence cognitive function and structural damage of the aging brain. However, existing data is inconsistent.Materials and Methods: This retrospective study explored the association between free plasma PUFA concentrations, cognitive function and brain structure atrophy in a well-characterized community-dwelling cohort of elderly individuals without stroke and dementia. Ten different fatty acids were analyzed in stored plasma samples from 391 non-demented elderly individuals by gas chromatography mass spectrometry. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in a subset of 167 individuals.Results: Higher plasma concentrations of free ω-6 PUFAs (p = 0.042), and, in particular, linoleic acid (p = 0.01), were significantly associated with lower executive function. No significant association existed between ω-3 PUFA concentrations and cognitive functioning. The volume of the frontal lobes was inversely associated with ω-6 PUFAs, whereas ω-3 PUFAs were positively related with temporal lobe volumes. All associations did not withstand correction for multiple comparisons.Conclusions: Our study suggests subtle effects of PUFA imbalances on cognition and brain structure. Yet the observed associations are weak and unlikely to be of clinical relevance. The brain regions that seem to be most sensitive to imbalances of ω-3 and ω-6 PUFAs are the frontal and temporal lobes.

Increased habitual flavonoid intake predicts attenuation of cognitive ageing in twins

BackgroundAlthough the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods.MethodsWe aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18–89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors.ResultsHigher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77; p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81; p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21; p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24; p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= −0.52, 95% CI 0.19, 0.84; p=0.001) and with faster simple reaction times (T3-T1= −18.1, 95% CI −35.4, −0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%, p=0.01) and proanthocyanidin (2.0%, p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years.ConclusionSmall increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing.

Self-reported subjective cognitive decline is associated with global cognition in a community sample of Latinos/as/x living in the United States

ABSTRACT Introduction Although subjective cognitive decline (SCD) may be an early risk marker of Alzheimer’s Disease (AD), research on SCD among Hispanics/Latinos/as/x (henceforth Latinos/as) living in the U.S. is lacking. We investigated if the cross-sectional relationship of self-reported SCD with objective cognition varies as a function of ethnic background (Latinos/as versus Non-Hispanic Whites [NHWs]). Secondary analyses conducted solely within the Latino/a group investigated if informant reported SCD is associated with objective cognition and whether self-reported SCD is related to markers of brain health in a sub-sample of Latinos/as with available MRI data. Methods Eighty-three participants (≥60 years of age) without dementia (35 Latinos/as; 48 NHWs) completed the Mattis Dementia Rating Scale (MDRS) and the Subjective Cognitive Decline-Questionnaire (SCD-Q). Additionally, 22 Latino/a informants completed the informant-version of the SCD-Q. Hierarchical regression models investigated if ethnicity moderates the association of MDRS and SCD-Q scores after adjusting for demographics and depressive symptoms. Correlational analyses within the Latino/a group investigated self- and informant-reported associations of SCD-Q scores with objective cognition, and associations of self-reported SCD-Q scores with medial temporal lobe volume and thickness. Results Latinos/as had lower education and MDRS scores than NHWs. Higher SCD-Q scores were associated with lower MDRS scores only in Latinos/as. Within the Latino/a group, self, but not informant reported SCD was related to objective cognition. Medium to large effect sizes were found whereby higher self-reported SCD was associated with lower entorhinal cortex thickness and left hippocampal volume in Latinos/as. Conclusions The association of SCD and concurrent objectively measured global cognition varied by ethnic background and was only significant in Latinos/as. Self-reported SCD may be an indicator of cognitive and brain health in Latinos/as without dementia, prompting clinicians to monitor cognition. Future studies should explore if SCD predicts objective cognitive decline in diverse groups of Latinos/as living in the U.S.

Cortical hypometabolism reflects local atrophy and tau pathology in symptomatic Alzheimer's disease.

Posterior cortical hypometabolism measured with 18F-fluorodeoxyglucose (FDG)-PET is a well-known marker of Alzheimer's disease-related neurodegeneration, but its associations with underlying neuropathological processes are unclear. We assessed cross-sectionally the relative contributions of three potential mechanisms causing hypometabolism in the retrosplenial and inferior parietal cortices: local molecular (amyloid and tau) pathology and atrophy, distant factors including contributions from the degenerating medial temporal lobe or molecular pathology in functionally connected regions, and the presence of the apolipoprotein E (APOE) ε4 allele. Two hundred and thirty-two amyloid-positive cognitively impaired patients from two cohorts [University of California, San Francisco (UCSF), and Alzheimer's Disease Neuroimaging Initiative (ADNI)] underwent MRI and PET with FDG, amyloid-PET using 11C-Pittsburgh Compound-B, 18F-florbetapir or 18F-florbetaben, and 18F-flortaucipir tau-PET in 1 year. Standard uptake value ratios (SUVRs) were calculated using tracer-specific reference regions. Regression analyses were run within cohorts to identify variables associated with retrosplenial or inferior parietal FDG standard uptake value ratios. On average, ADNI patients were older and were less impaired than the UCSF patients. Regional patterns of hypometabolism were similar between cohorts, although there were cohort differences in regional grey matter atrophy. Local cortical thickness and tau-PET (but not amyloid-PET) were independently associated with both retrosplenial and inferior parietal FDG SUVRs (ΔR2 = 0.09 to 0.21) across cohorts in models that also included age and disease severity (local model). Including medial temporal lobe volume improved the retrosplenial FDG model in the ADNI cohort (ΔR2 = 0.04, P = 0.008) but not for the UCSF (ΔR2 < 0.01, P = 0.52), and did not improve the inferior parietal models (ΔR2 < 0.01, P > 0.37). Interaction analyses revealed that medial temporal volume was more strongly associated with retrosplenial FDG SUVRs at earlier disease stages (P = 0.06 in UCSF, P = 0.046 in ADNI). Exploratory analyses across the cortex confirmed overall associations between hypometabolism and local tau pathology and thickness and revealed associations between medial temporal degeneration and hypometabolism in retrosplenial, orbitofrontal and anterior cingulate cortices. Finally, our data did not support hypotheses of a detrimental effect of pathology in connected regions or of an effect of the APOE ε4 allele in impaired participants. Overall, in two independent groups of patients at symptomatic stages of Alzheimer's disease, cortical hypometabolism mainly reflected structural neurodegeneration and tau, but not amyloid, pathology.

Phonological Errors in Posterior Cortical Atrophy

Background: Posterior cortical atrophy (PCA) is an atypical variant of Alzheimer’s disease (AD) that presents with visuospatial/perceptual deficits. PCA is characterized by atrophy in posterior brain regions, which overlaps with atrophy occurring in logopenic variant of primary progressive aphasia (lvPPA), another atypical AD variant characterized by language difficulties, including phonological errors. Language abnormalities have been observed in PCA, although the prevalence of phonological errors is unknown. We aimed to compare the frequency and severity of phonological errors in PCA and lvPPA and determine the neuroanatomical correlates of phonological errors and language abnormalities in PCA. Methods: The presence and number of phonological errors were recorded during the Boston Naming Test and Western Aphasia Battery repetition subtest in 27 PCA patients and 27 age- and disease duration-matched lvPPA patients. Number of phonological errors and scores from language tests were correlated with regional gray matter volumes using Spearman correlations. Results: Phonological errors were evident in 55% of PCA patients and 70% of lvPPA patients, with lvPPA having higher average number of errors. Phonological errors in PCA correlated with decreased left inferior parietal and lateral temporal volume. Naming and fluency were also associated with decreased left lateral temporal lobe volume. Conclusions: Phonological errors are common in PCA, although they are not as prevalent or severe as in lvPPA, and they are related to involvement of left temporoparietal cortex. This highlights the broad spectrum of clinical symptoms associated with AD and overlap between PCA and lvPPA.

Anti-NMDA receptor encephalitis and brain atrophy in children and adults: A quantitative study

PurposeTo determine whether brain atrophy was present in patients with anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) using qualitative and quantitative analyses of brain magnetic resonance imaging (MRI) and to explore clinical differences in patients with anti-NMDARE with or without brain atrophy. MethodsA retrospective observational study encompassing the serologic, cerebrospinal fluid, and brain MRI data of 23 patients with anti-NMDARE was conducted. Median patient age was 14 years (interquartile range [IQR], 12 years). The cohort included 15 children (<18 years old) and 8 adults (≥18 years old). There were 6 male and 17 female patients. Imaging analysis involved 2 expert readers' observations of MRIs and automated volumetric quantification using NeuroQuant (CorTechs Labs, Inc.) software. ResultsOf 23 pediatric and adult patients, 11 patients had 14 brain MRIs that were quantitatively analyzed. Quantitative NeuroQuant volumetric analysis showed atrophy in 9 of 14 MRIs for 7 of 11 patients compared to age-controlled normative data. In these 9 MRIs, atrophy was present in the temporal lobes (n = 9), cerebral cortex (n = 3), and cerebellum (n = 3). Qualitative analysis of 59 MRIs (23 patients) revealed volume loss in 6 patients: 5 with global cerebral and temporal lobe volume loss and 1 with temporal lobe volume loss. No patient showed cerebellar volume loss on qualitative analysis. Mean length of stay in the intensive care unit was not significantly different for patients with or without quantitative volume loss (3.5 [5.2] vs 27.4 [23.4] days; p = 0.08). ConclusionsIn this cohort of patients with anti-NMDARE, quantitative volumetric analysis showed brain atrophy, particularly affecting the temporal lobes, in 64% (7/11) of the patients. Qualitative analysis showed brain atrophy in 26% (6/23). These findings highlight the increased sensitivity of quantitative methods for volume loss detection. Larger studies are needed.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men.

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators.Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50–70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)].Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits.Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.

Normal tissue complication probability (NTCP) models for predicting temporal lobe injury after intensity-modulated radiotherapy in nasopharyngeal carcinoma: A large registry-based retrospective study from China

PurposeTo develop predictive models with dosimetric and clinical variables for temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Materials and methodsData of 8194 NPC patients who received IMRT-based treatment were retrospectively reviewed. TLI was diagnosed by magnetic resonance imaging. Dosimetric factors were selected by penalized regression and machine learning, with area under the receiver operating curve (AUC) calculated. Cox proportional hazards models containing the most predictive dosimetric factor with/without clinical variables were performed. A nomogram was generated as a visualization of Cox regression for predicting TLI-free survival. ResultsDuring median follow-up of 66.8 months (interquartile range [IQR] 54.2–82.2 months), 12.1% of patients (989/8194) developed TLI. Median latency from IMRT to TLI was 36 months (IQR 28–47 months). D0.5cc (dose delivered to 0.5-cm3 temporal-lobe volume) was the most predictive dosimetric factor (AUC: 0.799). Tolerance dose for 5% and 50% probabilities to develop TLI in 5 years were 65.06 Gy (95% confidence interval [CI]: 64.19–65.92) and 89.75 Gy (95% CI: 87.39–92.11), respectively. A nomogram comprising age, T stage, and D0.5cc significantly outperformed the model with only D0.5cc in predicting TLI (C-index: 0.78 vs. 0.737 in train set; 0.775 vs. 0.73 in test set; both P < 0.001). The nomogram-defined high-risk group had worse 5-year TLI-free survival. ConclusionsD0.5cc of 65.06 Gy was the tolerance dose of the temporal lobe. Reducing D0.5cc decreased risk of TLI, especially in older patients with advanced T stage. The nomogram could predict TLI precisely and allow individualized follow-up management.

Grey and white matter associations of psychotic-like experiences in a general population sample (UK Biobank)

There has been a substantial amount of research reporting the neuroanatomical associations of psychotic symptoms in people with schizophrenia. Comparatively little attention has been paid to the neuroimaging correlates of subclinical psychotic symptoms, so-called “psychotic-like experiences” (PLEs), within large healthy populations. PLEs are relatively common in the general population (7–13%), can be distressing and negatively affect health. This study therefore examined gray and white matter associations of four different PLEs (auditory or visual PLEs, and delusional ideas about conspiracies or communications) in subjects of the UK Biobank study with neuroimaging data (N = 21,390, mean age = 63 years). We tested for associations between any PLE (N = 768) and individual PLEs with gray and white matter brain structures, controlling for sex, age, intracranial volume, scanning site, and position in the scanner. Individuals that reported having experienced auditory hallucinations (N = 272) were found to have smaller volumes of the caudate, putamen, and accumbens (β = −0.115–0.134, pcorrected = 0.048–0.036), and reduced temporal lobe volume (β = −0.017, pcorrected = 0.047) compared to those that did not. People who indicated that they had ever believed in unreal conspiracies (N = 111) had a larger volume of the left amygdala (β = 0.023, pcorrected = 0.038). Individuals that reported a history of visual PLEs (N = 435) were found to have reduced white matter microstructure of the forceps major (β = −0.029, pcorrected = 0.009), an effect that was more marked in participants who reported PLEs as distressing. These associations were not accounted for by diagnoses of psychotic or depressive illness, nor the known risk factors for psychotic symptoms of childhood adversity or cannabis use. These findings suggest altered regional gray matter volumes and white matter microstructure in association with PLEs in the general population. They further suggest that these alterations may appear more frequently with the presentation of different psychotic symptoms in the absence of clinically diagnosed psychotic disorders.

The Impact of Sleep Disturbance on Regional Brain Volumes

Sleep disruption has been associated with increased beta-amyloid deposition and greater risk for later development of Alzheimer’s disease. Studies indicate that sleep disturbance correlates with regional brain volumes, but data are limited. We sought to determine the effect of sleep disturbance on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status. We conducted a secondary analysis of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set using complete structural imaging data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of sleep disturbance (via Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Sleep disruption was associated with greater volumes in the right and left lateral ventricles and greater volume of total white matter hyperintensities (p<.05). Lower mean volumes in total brain, total gray matter, and total cerebrum grey matter volumes, and in 12 hippocampal, frontal, parietal, and temporal lobe volumes were observed among participants who reported sleep disturbance. Males, Hispanic participants, and those with less education were more likely to report sleep disruption. Cognitive status moderated the relationship between sleep disturbance and lateral ventricular volumes, while APOE e4 moderated the effect between sleep disturbance and parietal lobe volumes. These findings suggest that disrupted sleep is associated with atrophy across multiple brain regions and ventricular hydrocephalus ex vacuo, after controlling for intracranial volume and demographic covariates. The influence of cognition and APOE e4 status indicates that this relationship is affected by co-occurring physiological processes.

The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

Subjective cognitive decline is associated with longitudinal cerebral blood flow reductions and gray matter atrophy in older adults

AbstractBackgroundSubjective cognitive decline (SCD), a potential harbinger of Alzheimer’s disease (AD), has been cross‐sectionally associated with neurodegeneration and cerebrovascular disease markers on brain MRI. However, longitudinal associations are less clear with few existing studies that yield inconsistent findings. Here, we related baseline SCD to longitudinal structural and hemodynamic markers of brain health in older adults free of clinical dementia and stroke.MethodsVanderbilt Memory &amp; Aging Project participants (n=299,72±7 years, 58% male) completed a baseline SCD protocol and multimodal 3T brain MRI, including T 1‐weighted imaging (grey matter volumes) and pseudo‐continuous arterial spin labeling (cerebral blood flow (CBF)) at baseline and multiple follow‐ups (18‐months, 3‐years, 5‐years). Baseline SCD (total and subdomain memory, language, and executive functioning scores) was longitudinally related to global and regional grey matter volumes and CBF (mL/100g/min). Linear mixed effects models, with random intercepts and slopes and a follow‐up time interaction, covaried for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein E (APOE)‐e4 status. Grey matter volume models covaried for intracranial volume. CBF models covaried for associated tissue volume.ResultsMean follow‐up time was 3.8 years. Higher total SCD predicted hippocampal volume reductions (p=0.04), increased inferior lateral ventricular volume (p&lt;0.001; Figure 1A), and global CBF reductions (p&lt;0.001; Figure 1B). Higher scores within each SCD domain predicted hippocampal volume reductions, increased inferior lateral ventricular volume, and global CBF reductions (p‐values&lt;0.04). Higher executive functioning‐SCD related only to frontal and occipital CBF reductions (p‐values&lt;0.003; Figure 1C) but not temporal CBF or lobar atrophy (p‐values&gt;0.07). Language‐SCD predicted reduced frontal CBF (p=0.01; Figure 1D) and temporal lobe volume (p=0.02). Surprisingly, memory‐SCD was not associated with temporal lobe volume or CBF (p‐values&gt;0.05). Sensitivity analyses excluding outliers revealed the same associations.ConclusionsHigher baseline SCD predicted multiple pathways of longitudinal brain changes, including cerebral hemodynamics and volume loss within areas first affected by AD. Executive functioning‐SCD predicted hemodynamic changes and language‐SCD related to alterations within the frontal and temporal lobes. Results suggest the relevance of considering the type of SCD, as specific domains may predict different pathologies over time with important prognostic implications. Future research is needed to understand the clinical consequences of these findings.

Subjective cognitive decline correlates with medial temporal lobe and hippocampal subfield volumetry in cognitively unimpaired participants

AbstractBackgroundSubjective cognitive decline (SCD) is a risk factor for cognitive decline and AD. SCD individuals display lower medial temporal lobe (MTL) volumes. Some features of SCD (SCDplus), such as specific worry and recent onset, have been proposed as more related to AD pathology. In this study we aimed to explore the differences in MTL volumes between SCD and control individuals and their associations with memory performance in a large sample of cognitively unimpaired subjects.Methods603 cognitively unimpaired individuals from a population‐based study (age: [47‐76], mean: 60.04∓6.57) underwent structural MRI, clinical and neuropsychological assessments. 184 were classified as SCD or 419 as Controls by their answers to the question “Do you perceive difficulties in memory or cognition as compared to how they used to be?”. A subgroup of 31 fulfilling two SCDplus criteria (Worry and Onset within last 5 years) was defined. Memory performance was assessed with the Free and Cued Selective Reminding Test (FCSRT).MTL and HS were segmented using ASHS using T1 and IR sequences. We compared regional volumes across SCD groups using linear models. Age, sex, education, APOE carriership and total intracranial volume were included as covariates. SCD group*memory scores interactions were assessed.ResultsSCD subjects showed lower volumes than Controls in right CA1 (p=0.031) and subiculum (p=0.026) (Figure 1). SCDplus subjects showed larger BA36 volumes in both hemispheres (Figure 2). In models comparing Controls and SCDplus we found a significant interaction (p=0.021) between SCDplus status and parahippocampal (PHC) bilateral volumes on FCSRT free recall score, with positive association in Controls and negative in SCDplus (poorer performance associated with larger PHC) (Figure 3).ConclusionAs previously reported in smaller and older samples (Schwarz et al, AAIC 2019) a reduction of CA1 and subiculum was found in SCD subjects. Moreover, PHC volume correlates negatively with memory performance in SCDplus: this may pinpoint a transitional phase in the AD continuum with increments of cortical volume, as described in (Gispert et al., 2015; Fortea et al., 2011). Further work including CSF biomarkers will assess how these associations may be mediated by AD pathology.

Different Patterns of Gray Matter Volume Reduction in Early-onset and Late-onset Alzheimer Disease.

Individuals with early-onset Alzheimer disease (EOAD) differ from those with late-onset Alzheimer disease (LOAD) not only in genetics and age at onset but also in their clinical symptoms. To differentiate the neuropathological and neurocognitive features of EOAD and LOAD by comparing the pattern of regional gray matter volume (GMV) reduction and its symptomatic correlates. Three-dimensional T1-weighted MRIs and Mini-Mental State Examination (MMSE) scores were obtained from 12 individuals with EOAD, 65 with LOAD, and 49 healthy controls (HC). Regional GMV reduction between the three groups was assessed using voxel-based morphometry. Multiple regression analyses were conducted with MMSE total score as an independent variable. Compared to the HC, both AD groups showed a significant GMV reduction in the bilateral hippocampus and the left temporoparietal junction; in addition, the LOAD group showed one in the bilateral anterior temporal lobes. Multiple regression analyses revealed a positive correlation between MMSE total score and GMV in the left anterior temporal lobe in both AD groups; that is, lower scores were associated with reduced GMV. Interestingly, a positive correlation in hippocampal GMV was revealed only in the LOAD group. MMSE total score is associated with the anterior temporal lobe volume in individuals with AD. Hippocampal volume and its relationship with MMSE total score are associated with LOAD pathophysiology but not EOAD pathophysiology. The hippocampal volume reduction and low MMSE scores are hallmarks of LOAD but are less specific to EOAD, which may cause a delay in diagnosis.

Distinct patterns of gray matter atrophy in hippocampal sclerosis of aging and Alzheimer’s disease neuropathology

AbstractBackgroundHippocampal sclerosis of aging (HS) and Alzheimer’s Disease Neuropathology (ADNP) both contribute to dementia in the elderly but are difficult to distinguish in vivo. Currently, there are no established biomarkers for HS, and few studies have investigated the distinction between HS‐ and ADNP‐related patterns of brain atrophy. We hypothesized that HS‐related atrophy would be restricted to the hippocampus and surrounding structures, while ADNP‐related atrophy would be most pronounced in the lateral temporal and parietal lobes.MethodWe used data from the National Alzheimer’s Coordinating Center (NACC) (09/2005‐03/2017) and identified 134 participants with suitable 3D T1w MRI and autopsy data. HS pathology was available as present/absent and we defined ADNP as present by a combination of high Braak stage (V/VI) and CERAD neuritic plaque score (3). We used the Computational Anatomy Toolbox (CAT12) to segment the MRI scans into tissue types and generate gray matter density maps. We examined the following regions of interest (ROIs): hippocampus, parahippocampus, amygdala, temporal and parietal regions, and global tissues measures. Additionally, we performed a voxel‐based morphometry (VBM) analysis. We studied the relationship between volumes/densities and neuropathologies using multiple linear regression models while adjusting for sex, age, education, dementia status, years from MRI to death, and intracranial volume.Result Table 1 depicts participant characteristics. We found that HS, but not ADNP, was associated with the volumes of the hippocampus (HS P&lt;0.001, ADNP P=0.4), parahippocampus (anterior only, HS P=0.007, ADNP P=0.8), and amygdala (HS P=0.009, ADNP=0.2, Table 2). ADNP was significantly associated with lateral temporal lobe volumes, most strongly the inferior/middle temporal gyri. We found a trend of association between ADNP and gray matter atrophy (P=0.051). HS was significantly associated with white matter atrophy (P=0.001). We display the VBM results in Figure 1, which largely confirm the ROI results. Additionally, we found HS was associated with bilateral thalamic and insular regions and ADNP with the left amygdala and hippocampal tail atrophy.ConclusionWhile HS is strongly associated with atrophy of the hippocampus and surrounding structures, ADNP is associated with atrophy of lateral temporal lobe regions. These diverging atrophy patterns are potential biomarkers for differentiating these two clinically indistinguishable conditions during life.

Obesity and muscle may have synergic effect more than independent effects on brain volume in community-based elderly.

To evaluate the individual and combined effects of obesity and muscle mass on brain volume in a community-dwelling healthy older population. One thousand two hundred nine participants (M:F = 574:635, mean age 63.6 ± 6.9years) were included. The cross-sectional area of visceral fat (VF), the height-adjusted appendicular skeletal muscle mass (ASM/height2), and the ratio of thigh muscle to visceral fat (TM/VF) represented obesity, muscle mass, and their integrated value, respectively. Linear regression analysis was performed to establish associations between 215 brain compartment volumes and VF, ASM/height2, and TM/VF after adjusting for covariates. On regression analysis, TM/VF had a positive correlation to the volumes of temporal lobe and cerebellum. TM/VF was associated with volumes of 10 subcompartments. TM/VF was positively correlated with the volumes of left entorhinal cortex, right temporal pole and inferior temporal gyrus related to cognition (p< 0.05, respectively), and the volumes of cerebellum and right pallidum related to movement (p< 0.05, respectively). However, VF had a negative correlation to temporal lobe volume and ASM/height2 had no significant correlation to any of the brain lobes. VF and ASM/height2 were correlated with volumes of 5 subcompartments and one subcompartment, respectively, CONCLUSIONS: TM/VF reflects the integrated effect of obesity and muscle mass and is associated with the volume of more brain regions compared to indices of obesity or muscle mass alone. The positive effect of muscle mass and the negative effect of obesity change the volumes of brain regions related to cognition and movement which were not significantly affected by obesity or muscle mass alone. • If obesity and muscle mass were considered together, we could find more significant brain volume changes which were not found in obesity or muscle alone. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of entorhinal cortex, temporal pole, and inferior temporal gyrus related to cognition. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of cerebellum and pallidum related to movement.

Cognitive complaints are associated with smaller right medial temporal gray-matter volume in younger postmenopausal women.

Menopause is associated with increasing cognitive complaints and older women are at increased risk of developing Alzheimer disease compared to men. However, there is difficulty in early markers of risk using objective performance measures. We investigated the impact of subjective cognitive complaints on the cortical structure in a sample of younger postmenopausal women. Data for this cross-sectional study were drawn from the baseline visit of a longer double-blind study examining estrogen-cholinergic interactions in normal postmenopausal women. Structural Magnetic Resonance Imaging was acquired on 44 women, aged 50-60 years and gray-matter volume was defined by voxel-based morphometry. Subjective measures of cognitive complaints and postmenopausal symptoms were obtained as well as tests of verbal episodic and working memory performance. Increased levels of cognitive complaints were associated with lower gray-matter volume in the right medial temporal lobe (r = -0.445, P < 0.002, R = 0.2). Increased depressive symptoms and somatic complaints were also related to increased cognitive complaints and smaller medial temporal volumes but did not mediate the effect of cognitive complaints. In contrast, there was no association between performance on the memory tasks and subjective cognitive ratings, or medial temporal lobe volume. The findings of the present study indicate that the level of reported cognitive complaints in postmenopausal women may be associated with reduced gray-matter volume which may be associated with cortical changes that may increase risk of future cognitive decline. : Video Summary:http://links.lww.com/MENO/A626.

Worth the Wait: Delayed Recall after 1 Week Predicts Cognitive and Medial Temporal Lobe Trajectories in Older Adults.

Clinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics. Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044). Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx).