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Background: Age represents the largest risk factor for Alzheimer's disease (AD) but is typically treated as a covariate. Still, there are similarities between brain regions affected in AD and those showing accelerated decline in normal aging, suggesting that the distinction between the two might fall on a spectrum. Objective: Our goal was to identify regions showing accelerated atrophy across the brain and investigate whether these overlapped with regions involved in AD or where related to amyloid. Methods: We used a longitudinal sample of 137 healthy older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), who underwent magnetic resonance imaging (MRI). In addition, a total of 79 participants also had longitudinal positron emission tomography (PET) data. We computed linear-mixed effects models for brain regions declining faster than the average to investigate variability in the rate of change. Results: 23 regions displayed a 0.5 standard deviation (SD) above average decline over 2 years. Of these, 52% overlapped with regions showing similar decline in a matched AD sample. Beyond this, the left precuneus, right superior frontal, transverse temporal, and superior temporal sulcus showed accelerated decline. Lastly, atrophy in the precuneus was associated with increased amyloid load. Conclusions: Accelerated decline in normal aging might contribute to the detection of early signs of AD among healthy individuals. [ABSTRACT FROM AUTHOR]

The current investigation examined the self-concept and temporality in institutionalized and non-institutionalized elderly. Sixty-two participants divided into two groups according to their place of residence participated in the study. The analysis focused on psychopathological scales, on self-concept assessment, its positive or negative valence, its development and the time perspective. The results showed that the institutionalized group was defined more with descriptive evaluations, emotional states, and peripheral information. The non-institutionalized group described themselves more with traits and specific attributes. For some identity statements, the emotional valence between the two groups was significantly different. The institutionalized group is not turned towards a particular temporal perspective, unlike the non-institutionalized who is more forward-looking. Findings suggest that there are differences in self-expression and temporality in our sample. This exploratory study emphasizes the importance of taking into account the self of institutionalized elderly and the temporality in which they are projected upon entering an institution. [ABSTRACT FROM AUTHOR]

AbstractBackground: Knowledge is still lacking regarding the preferred method for evaluation of learning in the Rey Auditory Verbal Learning Test (RAVLT). Validity of different methods was examined by the effect size in differentiating diagnostic stages in memory clinic patients versus healthy adults and the strength of association between RAVLT performance and brain atrophy. Method: The study included individuals with dementia (n = 247), Mild Cognitive Impairment (MCI, n = 709), Subjective Cognitive Impairment (SCI, n = 175) and cognitively unimpaired adults serving as healthy controls (HC, n = 102). All patients went through a comprehensive clinical examination and neuropsychological assessment of cognition including episodic memory gauged with RAVLT and brain imaging of medial temporal atrophy, cortical atrophy, and white matter hyperintensity. Results: The standard method for evaluation of learning in RAVLT (summed score over five trials) together with the late learning method (mean of trials 4 and 5) were the two most powerful methods according to group differentiation (discriminant validity). Both methods also showed considerable association with medial temporal atrophy (construct validity). The initial RAVLT performance represented by results on trial 1 and the constant in regression analysis with the power function provided information regarding attention that was important for the separation of SCI and HC. Conclusions: The most favorable clinical utility was indicated by discriminant and construct validity by total learning (standard method) including both attention- and learning-related parts and late learning of RAVLT performance, while theoretical understanding of mental processes involved in RAVLT performance was provided by the distinction between initial versus the subsequent learning performance. [ABSTRACT FROM AUTHOR]

Background: One-carbon metabolism coenzymes may influence brain aging in cognitively unimpaired adults. Methods: Baseline data were used from the UK Biobank cohort. Estimated intake of vitamin B6, B12, and folate was regressed onto neural network functional connectivity in five resting-state neural networks. Linear mixed models tested coenzyme main effects and interactions with Alzheimer’s disease (AD) risk factors. Results: Increased B6 and B12 estimated intake were linked with less functional connectivity in most networks, including the posterior portion of the Default Mode Network. Conversely, higher folate was related to more connectivity in similar networks. AD family history modulated these associations: Increased estimated intake was positively associated with stronger connectivity in the Primary Visual Network and Posterior Default Mode Network in participants with an AD family history. In contrast, increased vitamin B12 estimated intake was associated with less connectivity in the Primary Visual Network and the Cerebello– Thalamo–Cortical Network in those without an AD family history. Conclusions: The differential patterns of association between B vitamins and resting-state brain activity may be important in understanding AD-related changes in the brain. Notably, AD family history appears to play a key role in modulating these relationships. [ABSTRACT FROM AUTHOR]

This study explores the roles of working memory, cognitive functions, and behavioral and psychological symptoms in the contexts of aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Employing a systematic review approach, insights were synthesized from diverse research perspectives. Furthermore, we aimed to investigate the association between changes in brain metabolism and cognitive score in ADNI dataset. Key findings indicate that assessment of recognition memory performance serves as a critical indicator for identifying MCI and tracking its progression to AD. Additionally, evaluating spatial working memory performance proves essential in monitoring advancement from MCI to AD stages. Furthermore, the study underscores that trends in performance on the Digit Symbol Substitution Test and the Sequencing Test among healthy adults, those with MCI, or dementia tend to converge around the age of 100. In instances of accelerated aging, neuronal loss varies across different cell groups and brain regions. The research concludes that in individuals experiencing mild to severe cognitive impairment, performance in balance, strength, and aerobic fitness correlates closely with working memory, while showing no significant association with episodic memory.

Objective: Voxel-based morphometry (VBM), surface-based morphometry (SBM), and radiomics are widely used in the field of neuroimage analysis, while it is still unclear that the performance comparison between traditional morphometry and emerging radiomics methods in diagnosing brain aging. In this study, we aimed to develop a VBM-SBM model and a radiomics model for brain aging based on cognitively normal (CN) individuals and compare their performance to explore both methods' strengths, weaknesses, and relationships. Methods: 967 CN participants were included in this study. Subjects were classified into the middle-aged group (n = 302) and the old-aged group (n = 665) according to the age of 66. The data of 360 subjects from the Alzheimer's Disease Neuroimaging Initiative were used for training and internal test of the VBM-SBM and radiomics models, and the data of 607 subjects from the Australian Imaging, Biomarker and Lifestyle, the National Alzheimer's Coordinating Center, and the Parkinson's Progression Markers Initiative databases were used for the external tests. Logistics regression participated in the construction of both models. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the two model performances. The DeLong test was used to compare the differences in AUCs between models. The Spearman correlation analysis was used to observe the correlations between age, VBMSBM parameters, and radiomics features. Results: The AUCs of the VBM-SBM model and radiomics model were 0.697 and 0.778 in the training set (p = 0.018), 0.640 and 0.789 in the internal test set (p = 0.007), 0.736 and 0.737 in the AIBL test set (p = 0.972), 0.746 and 0.838 in the NACC test set (p < 0.001), and 0.701 and 0.830 in the PPMI test set (p = 0.036). Weak correlations were observed between VBM-SBM parameters and radiomics features (p < 0.05). Conclusion: The radiomics model achieved better performance than the VBMSBM model. Radiomics provides a good option for researchers who prioritize performance and generalization, whereas VBM-SBM is more suitable for those who emphasize interpretability and clinical practice. [ABSTRACT FROM AUTHOR]

Background: The Cognitive Change Index (CCI) is a widely-used measure of self-perceived cognitive ability and change. Unfortunately, it is unclear if the CCI predicts future cognitive and clinical decline. Objective: We evaluated baseline CCI to predict transition from normal cognition to cognitive impairment in nondemented older adults and in predementia groups including, subjective cognitive decline, motoric cognitive risk syndrome, and mild cognitive impairment. Different versions of the CCI were assessed to uncover any differential risk sensitivity. We also examined the effect of ethnicity/race on CCI. Methods: Einstein Aging Study participants (N = 322, Mage = 77.57±4.96, % female=67.1, Meducation = 15.06±3.54, % non-Hispanic white = 46.3) completed an expanded 40-item CCI version (CCI-40) and neuropsychological evaluation (including Clinical Dementia Rating Scale [CDR], Montreal Cognitive Assessment, and Craft Story) at baseline and annual follow-up (Mfollow - up=3.4 years). CCI-40 includes the original 20 items (CCI-20) and the first 12 memory items (CCI-12). Linear mixed effects models (LME) and generalized LME assessed the association of CCI total scores at baseline with rate of decline in neuropsychological tests and CDR. Results: In the overall sample and across predementia groups, the CCI was associated with rate of change in log odds on CDR, with higher CCI at baseline predicting faster increase in the odds of being impaired on CDR. The predictive validity of the CCI broadly held across versions (CCI-12, 20, 40) and ethnic/racial groups (non-Hispanic black and white). Conclusions: Self-perception of cognitive change on the CCI is a useful marker of dementia risk in demographically/clinically diverse nondemented samples. All CCI versions successfully predicted decline. [ABSTRACT FROM AUTHOR]

Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate whether the age-effect within different cognitive domains was mediated by age-associated CSF markers for neurodegenerative changes. We fitted 10 mediation models using structural equation modeling to investigate this in a cohort of 137 healthy adults, aged 40–80 years, from the Norwegian Dementia Disease Initiation (DDI) study. Here, t-tau and NfL were defined as mediators between age and different cognitive tests. The models showed that NfL mediated the age-effect for CERAD learning and memory recall (learning: β = −0.395, p < 0.05; recall: β = −0.261, p < 0.01). No such effect was found in the other models. Our findings suggest that the age-related lower performance in verbal learning and memory may be linked to NfL-associated neurodegenerative changes in cognitively healthy adults. • CSF NfL mediates the relationship between age and verbal learning and memory. • White matter pathology seems to have a prominent role in normal aging. • T-tau is not significantly associated to neuropsychological test performance. • SCD seems to be less important in detecting objective cognitive deficits. [ABSTRACT FROM AUTHOR]

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The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults. [ABSTRACT FROM AUTHOR]

The glucocorticoid (GC) hypothesis posits that effects of stress and dysregulated hypothalamic-pituitary-adrenal axis activity accumulate over the lifespan and contribute to impairment of neural function and cognition in advanced aging. The validity of the GC hypothesis is bolstered by a wealth of studies that investigate aging of the hippocampus and decline of associated mnemonic functions. The prefrontal cortex (PFC) mediates working memory which also decreases with age. While the PFC is susceptible to stress and GCs, few studies have formally assessed the application of the GC hypothesis to PFC aging and working memory. Using parallel behavioral and molecular approaches, we compared the effects of normal aging versus chronic variable stress (CVS) on working memory and expression of genes that encode for effectors of glutamate and GABA signaling in male F344 rats. Using an operant delayed match-to-sample test of PFC-dependent working memory, we determined that normal aging and CVS each significantly impaired mnemonic accuracy and reduced the total number of completed trials. We then determined that normal aging increased expression of Slc6a11, which encodes for GAT-3 GABA transporter expressed by astrocytes, in the prelimbic (PrL) subregion of the PFC. CVS increased PrL expression of genes associated with glutamatergic synapses: Grin2b that encodes the GluN2B subunit of NMDA receptor, Grm4 that encodes for metabotropic glutamate receptor 4 (mGluR4), and Plcb1 that encodes for phospholipase C beta 1, an intracellular signaling enzyme that transduces signaling of Group I mGluRs. Beyond the identification of specific genes that were differentially expressed between the PrL in normal aging or CVS, examination of Log2 fold-changes for all expressed glutamate and GABA genes revealed a positive association between molecular phenotypes of aging and CVS in the PrL but no association in the infralimbic subregion. Consistent with predictions of the GC hypothesis, PFC-dependent working memory and PrL glutamate/GABA gene expression demonstrate comparable sensitivity to aging and chronic stress. However, changes in expression of specific genes affiliated with regulation of extracellular GABA in normal aging vs. genes encoding for effectors of glutamatergic signaling during CVS suggest the presence of unique manifestations of imbalanced inhibitory and excitatory signaling in the PFC. [ABSTRACT FROM AUTHOR]

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM–GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2–5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM–GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics. [ABSTRACT FROM AUTHOR]

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans. [ABSTRACT FROM AUTHOR]

• Higher blood GFAP is associated with lower neurite dispersion in grey matter. • Dispersion and complexity of neurites may be influenced by late life astrogliosis. • Negative links between GFAP and neurite complexity are observed mainly in females. Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aβ42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults. [ABSTRACT FROM AUTHOR]

Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed. [ABSTRACT FROM AUTHOR]

Objectives Cognitive flexibility declines with aging and is usually indicated by task switch costs including global and local switch costs. Cognitive flexibility in aging is associated with alterations in functional connectivity. However, whether different task-modulated connectivity mechanisms underlying global and local switch costs remain unclear. Methods Here we use the support vector machine to identify age-related functional connectivity in global and local switch costs between older (n = 32) and young adults (n = 33). Participants completed a cued task-switching task during the functional magnetic resonance imaging scan. Results Results show an age-related decline behaviorally in global but not in local switch costs. Moreover, distinct patterns of age-related alterations of connectivity were observed for each cost. Specifically, only multivariate changes in connectivity patterns were observed for local switch cost, whereas specific age-related connections were revealed for global switch cost. In older adults, the task-modulated left dorsal premotor cortex–left precuneus connectivity decreased, and the left inferior frontal junction–left inferior parietal sulcus connectivity correlated with decreased global switch cost. Discussion This study provides novel evidence for different neural patterns in global and local switch costs by illuminating connectivity mechanisms underlying cognitive flexibility in aging. [ABSTRACT FROM AUTHOR]

Quantifying the survival patterns of spiral ganglion cells (SGCs), the cell bodies of auditory-nerve fibers, is critical to studies of sensorineural hearing loss, especially in human temporal bones. The classic method of manual counting is tedious, and, although stereology approaches can be faster, they can only be used to estimate total cell numbers per cochlea. Here, a machine-learning algorithm that automatically identifies, counts, and maps the SGCs in digitized images of semi-serial human temporal-bone sections not only speeds the analysis, with no loss of accuracy, but also allows 3D visualization of the SGCs and fine-grained mapping to cochlear frequency. Applying the algorithm to 62 normal-aging human ears shows significantly faster degeneration of SGCs in the basal than the apical half of the cochlea. Comparison to fiber counts in the same ears shows that the fraction of surviving SGCs lacking a peripheral axon steadily increases with age, reaching more than 50% in the apical cochlea and almost 66% in basal regions. [ABSTRACT FROM AUTHOR]

The glucocorticoid (GC) hypothesis posits that effects of stress and dysregulated hypothalamic-pituitary-adrenal axis activity accumulate over the lifespan and contribute to impairment of neural function and cognition in advanced aging. The validity of the GC hypothesis is bolstered by a wealth of studies that investigate aging of the hippocampus and decline of associated mnemonic functions. The prefrontal cortex (PFC) mediates working memory which also decreases with age. While the PFC is susceptible to stress and GCs, few studies have formally assessed the application of the GC hypothesis to PFC aging and working memory. Using parallel behavioral and molecular approaches, we compared the effects of normal aging versus chronic variable stress (CVS) on working memory and expression of genes that encode for effectors of glutamate and GABA signaling in male F344 rats. Using an operant delayed match-to-sample test of PFC-dependent working memory, we determined that normal aging and CVS each significantly impaired mnemonic accuracy and reduced the total number of completed trials. We then determined that normal aging increased expression of Slc6a11, which encodes for GAT-3 GABA transporter expressed by astrocytes, in the prelimbic (PrL) subregion of the PFC. CVS increased PrL expression of genes associated with glutamatergic synapses: Grin2b that encodes the GluN2B subunit of NMDA receptor, Grm4 that encodes for metabotropic glutamate receptor 4 (mGluR4), and Plcb1 that encodes for phospholipase C beta 1, an intracellular signaling enzyme that transduces signaling of Group I mGluRs. Beyond the identification of specific genes that were differentially expressed between the PrL in normal aging or CVS, examination of Log2 fold-changes for all expressed glutamate and GABA genes revealed a positive association between molecular phenotypes of aging and CVS in the PrL but no association in the infralimbic subregion. Consistent with predictions of the GC hypothesis, PFC-dependent working memory and PrL glutamate/GABA gene expression demonstrate comparable sensitivity to aging and chronic stress. However, changes in expression of specific genes affiliated with regulation of extracellular GABA in normal aging vs. genes encoding for effectors of glutamatergic signaling during CVS suggest the presence of unique manifestations of imbalanced inhibitory and excitatory signaling in the PFC.

Defective brain glucose utilization is a hallmark of Alzheimer’s disease (AD) while Type II diabetes and elevated blood glucose escalate the risk for AD in later life. Isolating contributions of normal aging from coincident metabolic or brain diseases could lead to refined approaches to manage specific health risks and optimize treatments targeted to susceptible older individuals. We evaluated metabolic, neuroendocrine, and neurobiological differences between young adult (6 months) and aged (24 months) male rats. Compared to young adults, blood glucose was significantly greater in aged rats at the start of the dark phase of the day but not during the light phase. When challenged with physical restraint, a potent stressor, aged rats effected no change in blood glucose whereas blood glucose increased in young adults. Tissues were evaluated for markers of oxidative phosphorylation (OXPHOS), neuronal glucose transport, and synapses. Outright differences in protein levels between age groups were not evident, but circadian blood glucose was inversely related to OXPHOS proteins in hippocampal synaptosomes, independent of age. The neuronal glucose transporter, GLUT3, was positively associated with circadian blood glucose in young adults whereas aged rats tended to show the opposite trend. Our data demonstrate aging increases daily fluctuations in blood glucose and, at the level of individual differences, negatively associates with proteins related to synaptic OXPHOS. Our findings imply that glucose dyshomeostasis may exacerbate metabolic aspects of synaptic dysfunction that contribute to risk for age-related brain disorders.

IntroductionPublished reports of associations between β-amyloid (Aβ) and cortical integrity conflict. Tau biomarkers may help elucidate the complex relationship between pathology and neurodegeneration in aging.MethodsWe measured cortical thickness using magnetic resonance imaging, Aβ using Pittsburgh compound B positron emission tomography (PiB-PET), and tau using flortaucipir (FTP)-PET in 125 cognitively normal older adults. We examined relationships among PET measures, cortical thickness, and cognition.ResultsCortical thickness was reduced in PiB+/FTP+ participants compared to the PiB+/FTP- and PiB-/FTP- groups. Continuous PiB associations with cortical thickness were weak but positive in FTP- participants and negative in FTP+. FTP strongly negatively predicted thickness regardless of PiB status. FTP was associated with memory and cortical thickness, and mediated the association of PiB with memory.DiscussionPast findings linking Aβ and cortical thickness are likely weak due to opposing effects of Aβ on cortical thickness relative to tau burden. Tau, in contrast to Aβ, is strongly related to cortical thickness and memory.

IntroductionThe impact of bilingualism on executive function has been extensively discussed, but inconsistent evidence has been reported. These discrepancies may stem from the complexities of being bilingual and the various ways of measuring bilingual experiences. This study aims to clarify the debate by providing a systematic critique and analysis on how different measurements of bilingualism can lead to different results within the same group of bilinguals.MethodsWe tested 48 cognitively healthy (CH) and 43 cognitively impaired (CI) older adults (Mage = 73.25 and 79.72 years, respectively) using the color-shape switching task. We assessed bilingualism using six different methods based on dominant language usage: five categorical computations and one continuous measurement.Results and discussionThe results varied depending on the method of measuring bilingualism and the participant group. For CH older adults, a significant effect of bilingualism on cognition performance was observed only when using the categorical variable based on a cutoff of 70% dominant language usage, but not with other categorical computations or the continuous approach. For CI older adults, no effect of bilingualism was found, regardless of the type of measurement used. In summary, our results demonstrated that different measurements of language use can yield different results within the same group of bilinguals using a single task. Our study yielded important implications for bilingual research: the findings challenge the current methodologies used to describe bilingual experiences and call for care and consideration of context and the complexity when examining the effects of bilingual experience on executive functions.

Although gray matter atrophy is commonly observed with aging, it is highly variable, even among healthy people of the same age. This raises the question of what other factors may contribute to gray matter atrophy. Previous studies have reported that risk factors for cardiometabolic diseases are associated with accelerated brain aging. However, these studies were primarily based on standard correlation analyses, which do not unveil a causal relationship. While randomized controlled trials are typically required to investigate true causality, in this work, we investigated an alternative method by exploring data-driven causal discovery and inference techniques on observational data. Accordingly, this feasibility study used clinical and quantified gray matter volume data from 22,793 subjects from the UK biobank cohort without any known neurological disease. Our method identified that age, sex, body mass index (BMI), body fat percentage (BFP), and smoking exhibit a causal relationship with gray matter volume. Interventions on the causal network revealed that higher BMI and BFP values significantly increased the chance of gray matter atrophy in males, whereas this was not the case in females.

Genome-wide association studies have discovered common genetic variants associated with cognitive performance. Polygenic scores that summarize these discoveries explain up to 10% of the variance in cognitive test performance in samples of adults. However, the role these genetics play in cognitive aging is not well understood. We analyzed data from 168 cognitively healthy participants aged 23–77 years old, with data on genetics, neuropsychological assessment, and brain-imaging measurements from two large ongoing studies, the Reference Abilities Neural Networks, and the Cognitive Reserve study. We tested whether a polygenic index previously related to cognition (Cog PGI) would moderate the relationship between age and measurements of the cognitive domains extracted from a neuropsychological evaluation: fluid reasoning, memory, vocabulary, and speed of processing. We further explored the relationship of Cog PGI and age on cognition using Johnson–Neyman intervals for two-way interactions. Sex, education, and brain measures of cortical thickness, total gray matter volume, and white matter hyperintensity were considered covariates. The analysis controlled for population structure-ancestry. There was a significant interaction effect of Cog PGI on the association between age and the domains of memory (Standardized coefficient = −0.158, p-value = 0.022), fluid reasoning (Standardized coefficient = −0.146, p-value = 0.020), and vocabulary (Standardized coefficient = −0.191, p-value = 0.001). Higher PGI strengthened the negative relationship between age and the domains of memory and fluid reasoning while PGI weakened the positive relationship between age and vocabulary. Based on the Johnson–Neyman intervals, Cog PGI was significantly associated with domains of memory, reasoning, and vocabulary for younger adults. There is a significant moderation effect of genetic predisposition for cognition for the association between age and cognitive performance. Genetics discovered in genome-wide association studies of cognitive performance show a stronger association in young and midlife older adults. [ABSTRACT FROM AUTHOR]

Changes in the brain and spinal cord microvasculature during normal aging contribute to the "sensitive" nature of aged central nervous system tissue to ischemic insults. In this review, we will examine alterations in the central nervous system microvasculature during normal aging, which we define as aging without a dominant pathology such as neurodegenerative processes, vascular injury or disease, or trauma. We will also discuss newer technologies to improve the study of central nervous system microvascular structure and function. Microvasculature within the brain and spinal cord will be discussed separately as anatomy and physiology differ between these compartments. Lastly, we will identify critical areas for future studies as well as key unanswered questions. [ABSTRACT FROM AUTHOR]

Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.

Cytoarchitectural brain changes during normal aging remain poorly characterized, and it is unclear whether patterns of brain aging differ by sex. This study used restriction spectrum imaging to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99 years). Widespread associations with age in multiple diffusion compartments, including increased free water, decreased restricted and hindered diffusion, and reduced neurite complexity, were observed in the cortical gray matter, the white matter tracts, and the hippocampus. Age differences in cortical microstructure were largely independent of atrophy. Associations were mostly global, although foci of stronger effects emerged in the fornix, anterior thalamic radiation and commissural fibers, and the medial temporal, orbitofrontal, and occipital cortices. Age differences were stronger and more widespread for women than men, even after adjustment for education, hypertension, and body mass index. Restriction spectrum imaging may be a convenient, noninvasive tool for monitoring changes in diffusion properties that are thought to reflect reduced cellular fractions and neurite density or complexity, which occur with typical aging, and for detecting sex differences in patterns of brain aging.

The effects of normal aging on functional connectivity (FC) within various brain networks of gray matter (GM) have been well-documented. However, the age effects on the networks of FC between white matter (WM) and GM, namely WM-GM FC, remains unclear. Evaluating crucial properties, such as global efficiency (GE), for a WM-GM FC network poses a challenge due to the absence of closed triangle paths which are essential for assessing network properties in traditional graph models. In this study, we propose a bipartite graph model to characterize the WM-GM FC network and quantify these challenging network properties. Leveraging this model, we assessed the WM-GM FC network properties at multiple scales across 1,462 cognitively normal subjects aged 22–96 years from three repositories (ADNI, BLSA and OASIS-3) and investigated the age effects on these properties throughout adulthood and during late adulthood (age ≥70 years). Our findings reveal that (1) heterogeneous alterations occurred in region-specific WM-GM FC over the adulthood and decline predominated during late adulthood; (2) the FC density of WM bundles engaged in memory, executive function and processing speed declined with age over adulthood, particularly in later years; and (3) the GE of attention, default, somatomotor, frontoparietal and limbic networks reduced with age over adulthood, and GE of visual network declined during late adulthood. These findings provide unpresented insights into multi-scale alterations in networks of WM-GM functional synchronizations during normal aging. Furthermore, our bipartite graph model offers an extendable framework for quantifying WM-engaged networks, which may contribute to a wide range of neuroscience research.

Background and purpose: Our objective was to apply multi-compartment T2 relaxometry in cognitively normal individuals aged 20-80 years to study the effect of aging on the parenchymal CSF fraction (CSFF), a potential measure of the subvoxel CSF space. Materials and methods: A total of 60 volunteers (age range, 22-80 years) were enrolled. Voxel-wise maps of short-T2 myelin water fraction (MWF), intermediate-T2 intra/extra-cellular water fraction (IEWF), and long-T2 CSFF were obtained using fast acquisition with spiral trajectory and adiabatic T2prep (FASTT2) sequence and three-pool non-linear least squares fitting. Multiple linear regression analyses were performed to study the association between age and regional MWF, IEWF, and CSFF measurements, adjusting for sex and region of interest (ROI) volume. ROIs include the cerebral white matter (WM), cerebral cortex, and subcortical deep gray matter (GM). In each model, a quadratic term for age was tested using an ANOVA test. A Spearman's correlation between the normalized lateral ventricle volume, a measure of organ-level CSF space, and the regional CSFF, a measure of tissue-level CSF space, was computed. Results: Regression analyses showed that there was a statistically significant quadratic relationship with age for CSFF in the cortex (p = 0.018), MWF in the cerebral WM (p = 0.033), deep GM (p = 0.017) and cortex (p = 0.029); and IEWF in the deep GM (p = 0.033). There was a statistically highly significant positive linear relationship between age and regional CSFF in the cerebral WM (p < 0.001) and deep GM (p < 0.001). In addition, there was a statistically significant negative linear association between IEWF and age in the cerebral WM (p = 0.017) and cortex (p < 0.001). In the univariate correlation analysis, the normalized lateral ventricle volume correlated with the regional CSFF measurement in the cerebral WM (ρ = 0.64, p < 0.001), cortex (r = 0.62, p < 0.001), and deep GM (ρ = 0.66, p < 0.001). Conclusion: Our cross-sectional data demonstrate that brain tissue water in different compartments shows complex age-dependent patterns. Parenchymal CSFF, a measure of subvoxel CSF-like water in the brain tissue, is quadratically associated with age in the cerebral cortex and linearly associated with age in the cerebral deep GM and WM. [ABSTRACT FROM AUTHOR]

The increased incidence of dilated perivascular spaces (dPVSs) visible on MRI has been observed with advancing age, but the relevance of PVS dilatation to normal aging across the lifespan has yet to be fully clarified. In the current study, we sought to find out the age dependence of dPVSs by exploring changes in different characteristics of PVS dilatation across a wide range of age. For 1220 healthy subjects aged between 18 and 100 years, PVSs were automatically segmented and characteristics of PVS dilatation were assessed in terms of the burden, location, and morphology of PVSs in the white matter (WM) and basal ganglia (BG). A machine learning model using the random forests method was constructed to estimate the subjects' age by employing the PVS features. The constructed machine learning model was able to estimate the age of the subjects with an error of 9.53 years on average (correlation = 0.875). The importance of the PVS features indicated the primary contribution of the burden of PVSs in the BG and the additional contribution of locational and morphological changes of PVSs, specifically peripheral extension and reduced linearity, in the WM to age estimation. Indeed, adding the PVS location or morphology features to the PVS burden features provided an improvement to the performance of age estimation. The age dependence of dPVSs in terms of such various characteristics of PVS dilatation in healthy subjects could provide a more comprehensive reference for detecting brain disease‐related PVS dilatation. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) plays, perhaps, the most important role in the advanced aging process, cognitive impairment and pathogenesis of neurodegenerative disorders. The process generates tissue damage via specific mechanisms on proteins, lipids and nucleic acids of the cells. An imbalance between the excessive production of oxygen- and nitrogen-reactive species and antioxidants leads to a progressive decline in physiological, biological and cognitive functions. Accordingly, we need to design and develop favourable strategies for stopping the early aging process as well as the development of neurodegenerative diseases. Exercise training and natural or artificial nutraceutical intake are considered therapeutic interventions that reduce the inflammatory process, increase antioxidant capacities and promote healthy aging by decreasing the amount of reactive oxygen species (ROS). The aim of our review is to present research results in the field of oxidative stress related to physical activity and nutraceutical administration for the improvement of the aging process, but also related to reducing the neurodegeneration process based on analysing the beneficial effects of several antioxidants, such as physical activity, artificial and natural nutraceuticals, as well as the tools by which they are evaluated. In this paper, we assess the recent findings in the field of oxidative stress by analysing intervention antioxidants, anti-inflammatory markers and physical activity in healthy older adults and the elderly population with dementia and Parkinson's disease. By searching for studies from the last few years, we observed new trends for approaching the reduction in redox potential using different tools that evaluate regular physical activity, as well as antioxidant and anti-inflammatory markers preventing premature aging and the progress of disabilities in neurodegenerative diseases. The results of our review show that regular physical activity, supplemented with vitamins and oligomolecules, results in a decrease in IL-6 and an increase in IL-10, and has an influence on the oxidative metabolism capacity. In conclusion, physical activity provides an antioxidant-protective effect by decreasing free radicals and proinflammatory markers. [ABSTRACT FROM AUTHOR]

IntroductionBlood-brain barrier (BBB) breakdown is an early independent biomarker of human cognitive dysfunction, as found using gadolinium (Gd) as a contrast agent. Whether Gd accumulates in brains of individuals with an age-dependent BBB breakdown and/or mild cognitive impairment remains unclear.MethodsWe analyzed T1-weighted magnetic resonance imaging (MRI) scans from 52 older participants with BBB breakdown in the hippocampus 19-28 months after either cyclic or linear Gd agent.ResultsThere was no change in T1-weighted signal intensity between the baseline contrast MRI and unenhanced MRI on re-examination in any of the studied 10 brain regions with either Gd agent suggesting undetectable Gd brain retention.DiscussionGd does not accumulate in brains of older individuals with a BBB breakdown in the hippocampus. Thus, Gd agents can be used without risk of brain retention within a ∼2-year follow-up to study BBB in the aging human brain in relation to cognition and/or other pathologies.

Highlights The first phosphoproteome profiling of mouse livers during normal aging. A total of 5,685 phosphosites in 2,335 proteins were quantified in this study. A phosphorylation-regulated pathway network was constructed. Metabolism, secretion, and the cell cycle might be dysregulated during normal aging.

Objective: Older adults with exceptional memory function, designated "SuperAgers," include individuals over age 80, with episodic memory at least as good as individuals ages 50s–60s. The Northwestern University SuperAging cohort is defined by performance on an established test of verbal memory. The purpose of this study was to determine if superior verbal memory extends to nonverbal memory in SuperAgers by examining differences in the National Institutes of Health Toolbox® (NIHTB) between older adults with exceptional memory and those with average-for-age cognition. Method: SuperAgers (n  = 46) and cognitively average-for-age older adults (n  = 31) completed a comprehensive neuropsychological battery and the NIHTB Cognition module. Multiple linear regressions were used to examine differences on subtests between groups. Results: There was a significant effect of group on the Picture Sequence Memory score, (p = .007), such that SuperAgers had higher scores than cognitively average-for-age older adults. There were no other group effects across other non-episodic memory NIHTB Cognition measures. Conclusions: Findings from this study demonstrated stronger performance on the memory measure of the NIHTB in SuperAgers compared to cognitively average-for-age older adults demonstrating superior memory in not only verbal but also nonverbal episodic memory in this group. Additionally, this study adds to the literature validating the NIHTB in older adults, particularly in a novel population of adults over age 80 with exceptional memory. [ABSTRACT FROM AUTHOR]

This study compares semantic and phonological interference vulnerability across the full range of learning processes. Method: 43 controls aged 61–88 underwent a neuropsychological examination, French adaptation of the LASSI-L, and an experimental phonological test, the TIP-A. Paired sample t-tests, factorial ANOVA and hierarchical regressions were conducted, psychometric properties were calculated. Results: TIP-A efficiently generated phonological interference between concurrent word lists and was associated with short-term memory, unlike LASSI-L. On LASSI-L, proactive interference was higher than retroactive interference; the opposite pattern was found on TIP-A. Memory performance was better explained by age in the semantic than in the phonological task. Age was not associated with interference vulnerability. Intrusions and false recognition were associated with cognitive functioning regardless of age, particularly in the semantic context. Conclusion: To our knowledge, this is the first study to assess phonological and semantic interference using homologous concurrent word list tasks, and not a working memory build-up or DRM paradigm. The pattern obtained illustrates the weak initial memory trace in a phonological context and results are discussed according to depth-of-processing and dual-process theories. Similar paradigms could be studied among various pathologies for a better understanding of generalised interference vulnerability vs. specific semantic or phonological impairment. [ABSTRACT FROM AUTHOR]

Purpose: We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it. Design: Cross-sectional. Participants: Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems. Methods: In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging. Main Outcome Measures: Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°. Results: In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems. Conclusions: We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM–GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2–5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM–GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

The mammalian auditory cortex is necessary to resolve temporal features in rapidly-changing sound streams. This capability is crucial for speech comprehension in humans and declines with normal aging. Nonhuman primate studies have revealed detrimental effects of normal aging on the auditory nervous system, and yet the underlying influence on temporal processing remains less well-defined. Therefore, we recorded from the core and lateral belt areas of auditory cortex when awake young and old monkeys listened to tone-pip and noise-burst sound sequences. Elevated spontaneous and stimulus-driven activity were the hallmark characteristics in old monkeys. These old neurons showed isomorphic-like discharge patterns to stimulus envelopes, though their phase-locking was less precise. Functional preference in temporal coding between the core and belt existed in the young monkeys but was mostly absent in the old monkeys, in which old belt neurons showed core-like response profiles. Finally, the analysis of population activity patterns indicated that the aged auditory cortex demonstrated a homogenous, distributed coding strategy, compared to the selective, sparse coding strategy observed in the young monkeys. Degraded temporal fidelity and highly-responsive, broadly-tuned cortical responses could underlie how aged humans have difficulties to resolve and track dynamic sounds leading to speech processing deficits.

Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment. Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer's disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer's Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+. Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each. Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed. [ABSTRACT FROM AUTHOR]

In the aging process of normal people, the functional activity pattern of brain is in constant change, and the change of brain runs through the whole life cycle, which plays a crucial role in the track of individual development. In recent years, some studies had been carried out on the brain functional activity pattern during individual aging process from different perspectives, which provided an opportunity for the problem we want to study. In this study, we used the resting-state functional magnetic resonance imaging (rsfMRI) data from Cambridge Center for Aging and Neuroscience (Cam-CAN) database with large sample and long lifespan, and computed the functional connectivity (FC) values for each individual. Based on these values, the hemispheric similarity of functional connectivity (HSFC) obtained by Pearson correlation was used as the starting point of this study. We evaluated the ability of individual recognition of HSFC in the process of aging, as well as the variation trend with aging process. The results showed that HSFC could be used to identify individuals effectively, and it could reflect the change rule in the process of aging. In addition, we observed a series of results at the sub-module level and find that the recognition rate in the sub-module was different from each other, as well as the trend with age. Finally, as a validation, we repeated the main results by human brainnetome atlas (BNA) template and without global signal regression, found that had a good robustness. This also provides a new clue to hemispherical change patterns during normal aging. [ABSTRACT FROM AUTHOR]

Purpose: The goal of the current study was to introduce a new methodology that holds a promise to be used in hippocampus-aging studies using sub-millimeter super-resolution hybrid diffusion imaging (HYDI) MRI. Methods: HYDI diffusion data were acquired in two groups of older and younger healthy participants recruited from the Indiana Alzheimer's Disease Research Center and community. These data were then transformed into super-resolution diffusion images before the hippocampal subfield analyses. We studied the correlation between the subjects' age and the structural connectivity involving the hippocampal subfields and the connectivity between the whole hippocampus and the cerebral cortex. Results: Structural integrity derived from the tractography streamlines between the hippocampal subfields was reduced in older than younger adults. Conclusion: The findings offered a new promising framework, and they opened avenues for future studies to explore the relationship between the structural connectivity in the hippocampal area and different types of dementia. [ABSTRACT FROM AUTHOR]

• Odor identification and discrimination weakly predicted MoCA global cognitive status. • Weak olfactory influences on executive function irrespective of executive outcome. • One-point increase on odor test meant 1.09–1.29 greater odds of unimpaired MoCA. • Cognition is predicted by odor scores even in absence of age-related cognitive deficit. Olfactory and cognitive performance share neural correlates profoundly affected by physiological aging. However, whether odor identification and discrimination scores predict global cognitive status and executive function in healthy older people with intact cognition is unclear. Therefore, in the present study, we set out to elucidate these links in a convenience sample of 204 independently living, cognitively intact healthy Czech adults aged 77.4 ± 8.7 (61–97 years) over two waves of data collection (one-year interval). We used the Czech versions of the Montreal Cognitive Assessment (MoCA) to evaluate global cognition, and the Prague Stroop Test (PST), Trail Making Test (TMT), and several verbal fluency (VF) tests to assess executive function. As a subsidiary aim, we aimed to examine the contribution of olfactory performance towards achieving a MoCA score above vs. below the published cut-off value. We found that the MoCA scores exhibited moderate associations with both odor identification and discrimination. Furthermore, odor identification significantly predicted PST C and C/D scores. Odor discrimination significantly predicted PST C/D, TMT B/A, and standardized composite VF scores. Our findings demonstrate that olfaction, on the one hand, and global cognition and executive function, on the other, are related even in healthy older people. [ABSTRACT FROM AUTHOR]