Atrophy In Older Adults Research Articles

Associations between accelerated forgetting, amyloid deposition and brain atrophy in older adults.

Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer's disease pathology, and how memory selectivity may influence which material is forgotten. We assessed ALF in 'Insight 46', a sub-study of the MRC National Survey of Health and Development (a population-based cohort born during one week in 1946) (n=429; 47% female; assessed aged ∼73 years). ALF assessment comprised visual and verbal memory tests: Complex Figure Drawing and the Face-Name Associative Memory Exam (FNAME). ALF scores were calculated as the percentage of material retained after 7 days, relative to 30 minutes. In 306 cognitively-normal participants, we investigated effects on ALF of β-amyloid pathology (quantified using 18F-Florbetapir-PET, classified as positive/negative) and whole-brain and hippocampal atrophy rate (quantified from serial T1-MRI over ∼2.4 years preceding the ALF assessment), as well as interactions between these pathologies. We categorized Complex Figure Drawing items as 'outline' or 'detail', to test our hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. We also investigated associations between ALF and Subjective Cognitive Decline, measured with the MyCog questionnaire. Complex Figure 'outline' items were better retained than 'detail' items (mean retention over 7 days = 94% vs 72%). Amyloid-positive participants showed greater forgetting of the Complex Figure outline, compared to amyloid-negatives (90% vs 95%; P<0.01). There were interactions between amyloid pathology and cerebral atrophy, such that whole-brain and hippocampal atrophy predicted greater ALF on Complex Figure Drawing among amyloid-positives only (e.g. 1.9 percentage-points lower retention per ml/year of whole-brain atrophy [95% confidence intervals 0.5, 3.7]; P<0.05). Greater ALF on FNAME was associated with increased rate of hippocampal atrophy. ALF on Complex Figure Drawing also correlated with subjective cognitive decline (-0.45 percentage-points per MyCog point [-0.85, -0.05], P<0.05). These results provide evidence of associations between some measures of ALF and biomarkers of brain pathologies and subjective cognitive decline in cognitively-normal older adults. On Complex Figure Drawing, 'outline' items were better remembered than 'detail' items - illustrating the strategic role of memory selectivity - but 'outline' items were also relatively more vulnerable to ALF in individuals with amyloid pathology. Overall, our findings suggest that ALF may be a sensitive marker of cognitive changes in preclinical Alzheimer's disease.

Neurodegenerative Plasma Biomarkers for Prediction of Hippocampal Atrophy in Older Adults with Suspected Alzheimer's Disease in Kinshasa, Democratic Republic of Congo.

The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias-amyloid-β (Aβ42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)-to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC). Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer's Questionnaire (AQ). Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood samples collected at the study visit. Hippocampal volumes were measured using magnetic resonance imaging (MRI). General linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under the curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either individually or in combination in the models. Elevated p-tau181 was associated with left hippocampal (LH) atrophy p= 0.020). Only higher p-tau181 concentrations were significantly associated with 4.2-fold increased odds [OR=4.2 (1.5-18.4)] of hippocampal atrophy per standard deviation. The AUC of plasma biomarkers without clinical covariates to discriminate LH, RH, and total hippocampal (TH) or both hippocampi atrophy ranged between 90% to 94%, 76% to 82%, and 85% to 87%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, and TH ranged between 94%-96%, 81%-84%, and 88%-90%, respectively. These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa.

Reversal of Soleus Muscle Atrophy in Older Adults: A Non-Volitional Exercise Intervention for a Changing Climate.

The World Health Organization recommends that older adults undertake at least 150 minutes of moderate intensity physical activity over the course of each week in order to maintain physical, mental, and social health. This goal turns out to be very difficult for most community dwelling older adults to achieve, due to both actual and perceived barriers. These barriers include personal health limitations, confinement issues, and self-imposed restrictions such as fear of injury. Climate change exacerbates the confinement issues and injury fears among the elderly. To assist older adults in obtaining the benefits of increased physical activity under increasingly challenging climate conditions, we propose a targeted non-volitional intervention which could serve as a complement to volitional physical activity. Exogenous neuro-muscular stimulation of the soleus muscles is a non-invasive intervention capable of significantly increasing cardiac output in sedentary individuals. Long-term daily use has been shown to improve sleep, reduce bone loss, and reverse age-related cognitive decline, all of which are significant health concerns for older adults. These outcomes support the potential benefit of exogenous neuro-muscular stimulation as a complementary form of physical activity which older adults may find convenient to incorporate into their daily life when traditional forms of exercise are difficult to achieve due to barriers to completing traditional physical activities as a result of in-home or in-bed confinement, perceptual risks, or real environmental risks such as those arising from climate change.

Associations of anemia and cardiovascular disease with longitudinal changes in brain MRI markers and cognitive decline in older adults: A cohort study

AbstractBackgroundAnemia and cardiovascular disease (CVD) are two prevalent chronic conditions causing cerebral hypoxia in older adults. Although anemia and CVD often coexist in older people and potentially share underlying mechanisms, the independent effects of these two diseases with cognitive decline are largely unknown. The objective of this cohort study is to investigate the independent associations of anemia and CVD with cognitive decline in older adults, and further explore their associations with changes in MRI markers of brain aging using longitudinal MRI data.MethodThis cohort study used data from 2244 dementia‐ and stroke‐free participants in the population‐based Swedish National study on Aging and Care in Kungsholmen (age ≥60 years, female 62%). Participants were regularly followed from 2001‐2004 (baseline) through 2013‐2016. Anemia (WHO criteria) and CVD were determined at baseline. Cognitive function was assessed using a neuropsychological test battery across 12 years. A subset of participants (N = 503) underwent brain MRI examinations at baseline, and 327undertook follow‐up MRI scans after 3 and/or 6 years. Brain volumetric measures and markers of cerebral small vessel disease (cSVD) were assessed following standard methods. The associations of anemia or/and CVD with cognitive decline and changes in brain volume and cSVD markers were investigated using linear mixed‐effects models, while controlling for age, sex, lifestyle, vascular risk factors, chronic kidney disease, cancer, serum c‐reactive protein, and APOE genotype.ResultOf the 2244 participants, 5% had only anemia and 17% had only CVD. Both anemia and CVD were independently associated with a steeper decline in global cognitive composite score (anemia ‐0.01/year; 95%CI ‐0.03 to ‐0.00, CVD ‐0.02/year; 95%CI ‐0.03 to ‐0.02). Anemia was associated with faster decline in category fluency and perceptual speed, while CVD was significantly associated with an accelerated decline in all examined cognitive domains. Both anemia and CVD at baseline were associated with a steeper decline in total brain tissue volume, while CVD was additionally associated with steeper decline in volumes of hippocampus (P&lt;0.05). Neither was significantly associated with changes in cSVD markers (i.e., white‐matter hyperintensities, lacunes).ConclusionBoth anemia and CVD are risk factors for accelerated cognitive decline and brain atrophy in older adults.

Total and posterior cerebral blood flow is associated with white matter hyperintensity volume and Alzheimer’s‐like patterns of brain atrophy in older adults

AbstractBackgroundSmall vessel cerebrovascular disease, often visualized as white matter hyperintensities (WMH) on T2‐weighted MRI scans, contributes to risk, progression, and, possibly, pathogenesis of Alzheimer’s disease (AD). When considered in the context of previous neuroimaging biomarker work in AD, WMH appear to colocalize with other markers of disease risk and progression, including metabolic changes, atrophy, and tau pathology, in areas perfused by the posterior circulation. In the current study, we used a novel MR‐based method, termed phase contrast, to quantitate total cerebral blood flow in anterior and posterior circulations and test its relationship with WMH volume and an AD‐like pattern of brain atrophy in older, community‐dwelling adults.MethodTwo hundred forty‐five older adult participants (77±5.6 mean±SD age, 66% women, 42% Latinx, 30% Black, and 28% White individuals) in the Washington Heights Inwood Columbia Aging Project (WHICAP) received T1‐weighted, T2‐weighted (FLAIR), and phase contrast MR imaging. 2D phase contrast imaging can be used to quantify absolute blood flow rates with cross‐sectional velocity‐encoding of major vasculature leading into the brain. Blood flow rates in the anterior circulation (carotid arteries) and posterior circulation (vertebral arteries) were derived with Medis QFlow 4.0. WMH volume and cortical thickness in AD‐signature regions were derived with in‐house software and FreeSurfer v6.0, respectively. Separate general linear models tested the association of total, anterior, and posterior blood flow rates with WMH volumes and AD‐signature cortical thickness.ResultLower total cerebral blood flow was associated with increased total WMH volume (β = ‐0.14, p&lt;0.05, 95%CI [‐1.37E‐2, ‐7.32E‐4]), an effect that was stronger for posterior flow (β_posterior = ‐0.17, 95%CI [‐3.7E‐2, 2.5E3], β_anterior = ‐0.11, 95%CI [‐1.9E‐2, 5.4E3]). Lower posterior blood flow specifically was associated with lower AD‐signature cortical thickness, but only in older participants (age interaction term: β = ‐3.14, p&lt;0.01, 95%CI [‐2.0E‐4, ‐3.5E‐5]).ConclusionLower total cerebral blood flow, particularly in the posterior circulation, is associated with increased WMH volume and decreased cortical thickness, two neuroimaging markers that are implicated in risk and progression of AD. Future work that examines whether or how diminished total cerebral blood flow accounts for the colocalization of AD biomarkers across modalities will provide insight into the vascular contributions to AD.

Medial Temporal Lobe Atrophy in Older Adults With Subjective Cognitive Impairments Affects Gait Parameters in the Spatial Navigation Task.

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy.

Distinct Patterns of Brain Atrophy in MCR and amnestic MCI pre‐dementia syndromes

AbstractBackgroundBoth amnestic Mild Cognitive Impairment (aMCI) and the Motoric Cognitive Risk (MCR) syndrome are reliable predictors of Alzheimer’s Disease (AD). There is also some evidence for that MCR is a stronger predictor of vascular dementia (VaD) than AD. The current study directly compared cortical and hippocampal atrophy patterns in MCR and aMCI to inform the development of interventions targeted to these pre‐dementia syndromes. We hypothesized that MCR would be associated with a widespread pattern of cortical atrophy while aMCI would be associated with atrophy restricted to hippocampal and neighboring temporal regions.MethodCross‐sectional data from 733 older adults without dementia and functional disabilities from the MCR‐consortium were examined. MCR was operationalized as slow gait and subjective cognitive complaint, using previously established cohort‐specific criteria. aMCI was operationalized as 1.5 standard deviation or more below standardized performance on episodic memory measures. FreeSurfer v6.0 was applied to T‐1 weighted MRIs to examine cortical thickness and hippocampal atrophy patterns in MCR and aMCI relative to those without MCR and aMCI, respectively. Separate general linear models (GLMs) examined the associations between overall and regional cortical thickness, hippocampal volume, and MCR and aMCI. All GLMs were adjusted for age, sex, education, total intracranial volume, white matter lesion burden, and study site.ResultThe mean age of the sample was 74.4 years (45.4% women). The prevalence of MCR and aMCI was 7.6% and 2.6 %, respectively. Both MCR and aMCI was associated with overall cortical atrophy. Yet, while MCR was associated widespread cortical atrophy – that included prefrontal, insular, cingulate, motor, parietal and temporal regions – aMCI was associated with a restricted pattern of atrophy that primarily included temporal and hippocampal regions.ConclusionThis study revealed distinct patterns of atrophy in older adults with MCR and aMCI pre‐dementia syndromes. A widespread pattern of cortical atrophy – that is more consistent with VaD or mixed dementia than AD – was observed in MCR. A more restricted pattern of atrophy – that is more consistent with AD than VaD or mixed dementia – was observed in aMCI. Thus, the biological underpinnings of MCR and aMCI likely differ, and may require tailored interventions.

Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aβ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers.

Properties of the cognitive function battery for the MIND diet intervention to prevent Alzheimer’s disease

AbstractBackgroundOver the last several years, evidence has increasingly demonstrated the strong potential for dietary interventions to improve cognitive function over time. Nonetheless, our ability to measure this progress is limited by variability in cognitive assessments across studies. We evaluated the properties of the cognitive battery used in The MIND Diet Intervention to Prevent Alzheimer’s Disease. The MIND Diet Intervention is a randomized control trial designed to examine the efficacy of the MIND diet to slow cognitive decline and reduce brain atrophy in older adults at risk for Alzheimer’s dementia.MethodParticipants were 604 adults between 65 and 84 years old without cognitive impairment, who had a body mass index &gt; 25 k/m2, a family history of dementia and a suboptimal diet. They had an average of 17 years of education and were mostly white (89%) women (65%). Before randomization into one of two dietary intervention counseling sessions, participants completed an in‐person administration of the MIND cognitive battery of tests. The battery included 12 cognitive tests, measuring the four cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and statistical performance of participants on each domain. In order to further establish validity of each domain, we regressed the domain scores against the covariates of age, and years of education, and late life cognitive activity.ResultFour factors emerged in the principal component analyses that were similar to the theoretical domains. Rand’s statistic was 0.82 (p&lt;0.001), indicating a good fit between the factor analytic results and the hypothesized grouping. In regression analyses, we found the expected associations with age and late life cognitive activity with each of the four cognitive domains.ConclusionThese results suggest that the MIND cognitive battery is a comprehensive and efficient battery, which may perform well as an outcome measure in future intervention trials for older adults.

Effects of a physical activity intervention on brain atrophy in older adults at risk of dementia: a randomized controlled trial.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.

Properties of the Cognitive Function Battery for the MIND Diet Intervention to Prevent Alzheimer's Disease.

To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer's Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer's dementia. The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education. Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains. These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.

Hippocampal maintenance after a 12-month physical activity intervention in older adults: The REACT MRI study

BackgroundPhysical activity interventions have had varying results on modifying hippocampal volume. MethodsThe Retirement in Action (REACT) study conducted a randomised-controlled trial of a 12-month physical activity and behaviour maintenance intervention in older adults at risk of mobility impairments. The physical activity sessions were delivered twice weekly for the first twelve weeks, and then reduced to once weekly, to groups of 15 participants. Activities included cardiovascular, strength, balance and flexibility exercises. A sub-sample of participants in the physical activity (N = 54) and control arms (N = 48) underwent a 3 T MRI brain scan and cognitive assessments at baseline, 6- and 12-months (mean age = 76.6 years, 6.8 SD). It was hypothesised that the intervention would lead to a reduced rate of decline in hippocampal volume. Group differences in changes in cognition were also examined. ResultsAs hypothesised, we found a maintenance in left hippocampal volume in the intervention arm, in comparison with the control arm after 12 months (p = 0.027). In a secondary analysis, this effect was attenuated after including age, sex and education level as covariates (p = 0.057). There was no significant between-group difference in the right hippocampus (p = 0.405). Contrary to our hypothesis, we did not find a beneficial effect of the intervention on cognitive outcomes. ConclusionsOur findings suggest that a community-based physical activity intervention can significantly ward-off hippocampal atrophy in older adults. While the lack of effects on cognition may limit the interpretability of our results, our findings of hippocampal maintenance are promising given the potential clinical relevance of protecting the hippocampus from age-related decline.

Sarcopenia is independently associated with parietal atrophy in older adults

As populations age, sarcopenia becomes a major health problem among adults aged 65years and older. However, little information is available about the relationship between sarcopenia and brain structure abnormalities. The objective of this study was to investigate associations between sarcopenia and brain atrophy in older adults and relationships with regional brain areas. This prospective cohort study recruited 102 retirement community residents aged 65years and older. All participants underwent gait speed measurement, handgrip strength measurement and muscle mass measurement by dual X-ray absorptiometry. Diagnosis of sarcopenia was made according to criteria of the Asian Working Group for Sarcopenia (AWGSOP). All patients underwent magnetic resonance imaging (MRI), and images were analysed for global cortical atrophy (GCA) (range 0-3), parietal atrophy (PA) (range 0-3) and medial temporal atrophy (MTA) (range 0-4). Among 102 older adult participants (81.4±8.2years), 47 (46.1%) were diagnosed with sarcopenia according to AWGSOP criteria. The sarcopenia group had more moderate to severe PA (Grade 2: 19.1% vs. 5.5%; grade 3:6.4% vs. 0%, P=0.016) and GCA (Grade 2: 40.4% vs. 18.2%, P=0.003) and a trend of more moderate to severe MTA (Grade 2: 46.8% vs. 30.9%; grade 3: 8.5% vs. 1.8%, P=0.098) than the non-sarcopenia group. In univariate logistic regression, sarcopenia was significantly associated with PA (OR 5.94, 95% CI 1.56-22.60, P=0.009), GCA (OR 3.05, 95% CI 1.24-7.51, P=0.015), and MTA (OR 2.55, 95% CI 1.14-5.69, P=0.023). In multivariable logistic regression analysis, sarcopenia was an independent risk factor for PA (adjusted OR 6.90, 95% CI 1.30-36.47, P=0.023). After adjusting for all covariates, only age had a significant relationship with GCA (Adjusted OR 1.09, 95% CI 1.00-1.19, P=0.044) and MTA (Adjusted OR 1.09, 95% CI 1.01-1.17, P=0.022). This is the first study to explore associations between sarcopenia and global as well as regional brain atrophy in older adults. The sarcopenia group had higher rates of moderate to severe PA, GCA and MTA than the non-sarcopenia group. PA was significantly associated with sarcopenia in older adults. Further longitudinal studies are needed to address the mechanism and pathogenesis of brain atrophy and sarcopenia.

Longitudinal Trajectories in Cortical Thickness and Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy in Older Adults.

Background:Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable.Objective:Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years.Methods:Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study.Results:In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs.Conclusion:The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

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.

Plasma carotenoids and medial temporal lobe atrophy in older adults

AbstractBackgroundCarotenoids are vegetable pigments uniquely provided by diet which have antioxidant, immunomodulatory and specific neuroprotective properties. Carotenes (found in orange‐yellow fruits and vegetables) are precursors of retinoids, key signaling molecules for synaptic plasticity. The xanthophylls, lutein and zeaxanthin (found in green vegetables, orange‐yellow fruits and corn) cross the blood‐brain barrier, may decrease lipid peroxidation and stabilize lipid‐protein structures in neuronal membranes. Limited epidemiological studies on dietary carotenoids (assessed by questionnaires) reported inconsistent associations with brain aging using cognitive change as an outcome (and not neuroimaging or clinical dementia or Alzheimer’s disease diagnosis). However, blood carotenoids levels were associated with lower risk of dementia over 10 years, in a large cohort of older adults, the Three‐City (3C) study. Here, we further investigated whether blood carotenoids were also associated with the 10‐year atrophy of the medial temporal lobe (MTL), a central biomarker of neurodegeneration in aging.MethodWe included 461 dementia‐free participants from the 3C study (age ≥65), who had plasma carotenoid (α and β‐carotene, lycopene, lutein, zeaxanthin, β‐cryptoxanthin) measures at baseline and who underwent at least one of the three repeated brain imaging exams performed in the subsequent 10 years. Linear mixed models were used to assess the association between plasma carotenoids and MTL volume change assessed using FreeSurfer 5.1 segmentation software.ResultOver a median follow‐up of 5.1 years (maximum 11.8 years), higher plasma levels of total carotenoids and of β‐carotene were associated with lower decline in MTL volume (P = .04 and P = .008, respectively). The mean differences in MTL volume change for each increase of 1 SD were 0.02 (95% CI, 0.001; 0.04) cm3/year and 0.02 (0.01; 0.04) cm3/year for total carotenoids and β‐carotene, respectively. Other carotenoids were not significantly associated with MTL atrophy.ConclusionThe associations found between plasma total carotenoids and β‐carotene and 10‐year atrophy of the MTL in this large cohort of older adults suggest a beneficial role of carotenoids for the prevention of age‐related neurodegeneration.

Reliable change in neuropsychological test scores is associated with brain atrophy in older adults

The reliable change index (RCI) is a commonly used method for interpreting change in neuropsychological test scores over time. However, the RCI is a psychometric method that, to date, has not been validated against neuroanatomical changes. Longitudinal neuroimaging and neuropsychological data from baseline and one-year follow-up visits were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The RCI was used to identify participants showing reliable decline on memory (ADNI-Mem; N=450) and executive functioning (ADNI-EF; N=456) factor scores. For each factor score, two groups (reliable change vs. no reliable change) were matched on potential baseline confounding variables. Longitudinal neuroanatomical data were analysed using tensor-based morphometry. Analysis revealed that reliable change on ADNI-Mem was associated with atrophy in the medial temporal cortex, limbic cortex, temporal lobe and some regions of the parietal lobe. Similar atrophy patterns were found for reliable change on ADNI-EF, except that atrophy extended to the frontal lobe and the atrophy was more extensive and of higher magnitude. The current study not only validates clinical usage of the RCI with neuroanatomical evidence of associated underlying brain change but also suggests patterns of likely brain atrophy when reliable cognitive decline is detected.

Plasma carotenoids and medial temporal lobe atrophy in older adults

Carotenoids are vegetable pigments with neuroprotective properties. Clinical studies found efficacy of specific carotenoids on improving brain perfusion and functioning with aging. However, evidence of an effect on neurodegeneration, which may require longer follow-up period to observe, is more limited. Leveraging biomarkers from a large population-based cohort study of older adults, we investigated whether blood carotenoids were associated with atrophy of the medial temporal lobe (a biomarker of neurodegeneration in aging) over 10 years. This study included 461 dementia-free participants from the Three-City Bordeaux study (aged ≥65) who had plasma carotenoids measured at baseline and up to three repeated brain imaging exams in the subsequent 10 years. In adjusted linear mixed models, each increase of 1 SD in plasma level of total carotenoids and of β-carotene was associated with 0.02cm3 (95% CI, 0.001-0.04; P=0.04) and 0.02cm3 (95% CI, 0.01-0.04; P=0.008) smaller medial temporal lobe volume loss per year, respectively. Our results based on a unique long-term prospective evaluation of a neuroimaging biomarker suggest a beneficial role of carotenoids for the prevention of age-related neurodegeneration.

Increased functional connectivity supports language performance in healthy aging despite gray matter loss

Although language is quite preserved from aging, it remains unclear whether age-related differences lead to a deterioration or reorganization in language functional networks, or to different dynamics with other domains (e.g., the multiple-demand system). The present study is aimed at examining language networks, using resting-state functional magnetic resonance imaging in typical aging in relation to language performance. Twenty-three (23) younger adults and 24 healthy older adults were recruited. Volumetric gray matter differences between the 2 groups were assessed using voxel-based morphometry. Then, seed-based analyses, integrated local correlations in core regions of the language network, and within- and between-network connectivity were performed. We expected less extended connectivity maps, local coherence diminution, and higher connectivity with the multiple-demand system in older adults. On the contrary, analyses showed language network differences in healthy aging (i.e., increased connectivity with areas inside and outside language network), but no deterioration, despite widespread atrophy in older adults. Integrated local correlation revealed alterations that were unnoticeable with other analyses. Although gray matter loss was not correlated with language performance, connectivity differences were positively correlated with fluency performance in the older group. These results differ from the literature concerning other cognitive networks in aging in that they show extra internetwork connections without a decrease in intranetwork language connections. This reorganization could explain older adults' good language performance and could be interpreted in accordance with the scaffolding theory of aging and cognition.

Countering disuse atrophy in older adults with low-volume leucine supplementation.

Older adults are at increased risk of being bedridden and experiencing negative health outcomes including the loss of muscle tissue and functional capacity. We hypothesized that supplementing daily meals with a small quantity (3-4 g/meal) of leucine would partially preserve lean leg mass and function of older adults during bed rest. During a 7-day bed rest protocol, followed by 5 days of inpatient rehabilitation, healthy older men and women (67.8 ± 1.1 yr, 14 men; 6 women) were randomized to receive isoenergetic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control (CON, 0.06 g/kg/meal; n = 10). Outcomes were assessed at baseline, following bed rest, and after rehabilitation. Body composition was measured by dual-energy X-ray absorptiometry. Functional capacity was assessed by knee extensor isokinetic and isometric dynamometry, peak aerobic capacity, and the short physical performance battery. Muscle fiber type, cross-sectional area, signaling protein expression levels, and single fiber characteristics were determined from biopsies of the vastus lateralis. Leucine supplementation reduced the loss of leg lean mass during bed rest (LEU vs. CON: -423 vs. -1035 ± 143 g; P = 0.008) but had limited impact on strength or endurance-based functional outcomes. Similarly, leucine had no effect on markers of anabolic signaling and protein degradation during bed rest or rehabilitation. In conclusion, providing older adults with supplemental leucine has minimal impact on total energy or protein consumption and has the potential to partially counter some, but not all, of the negative effects of inactivity on muscle health.NEW & NOTEWORTHY Skeletal muscle morphology and function in older adults was significantly compromised by 7 days of disuse. Leucine supplementation partially countered the loss of lean leg mass but did not preserve muscle function or positively impact changes at the muscle fiber level associated with bed rest or rehabilitation. Of note, our data support a relationship between myonuclear content and adaptations to muscle atrophy at the whole limb and single fiber level.