Cognitively Healthy Individuals Research Articles

Force Fluctuations During Role-Differentiated Bimanual Movements Reflect Cognitive Impairments in Older Adults: A Cohort Sequential Study.

During role-differentiated bimanual movements (RDBM), an object is typically stabilized with 1 hand and manipulated with the other. RDBM require coupling both hands for coordinated action (achieved through interhemispheric connections), but also inhibition of crosstalk to avoid involuntary movements in the stabilizing hand. We investigated how healthy cognitive aging and mild cognitive impairments (MCI) affect force stabilization during an RDBM in a cohort sequential study design with up to 4 measurement points over 32 months. In total, 132 older adults (>80 years) participated in this study, 77 were cognitively healthy individuals (CHI) and 55 presented with MCI. Participants performed a visuomotor bimanual force-tracking task. They either produced a constant force with both hands (bimanual constant) or a constant force with 1 and an alternating force with the other hand (role-differentiated). We investigated force fluctuations of constant force production using the coefficient of variation (CV), detrended fluctuation analysis (DFA), and sample entropy (SEn). Results showed higher CV and less complex variability structure (higher DFA and lower SEn) during the role-differentiated compared to the bimanual constant task. Furthermore, CHI displayed a more complex variability structure during the bimanual constant, but a less complex structure during the role-differentiated task than MCI. Interestingly, this complexity reduction was more pronounced in CHI than MCI individuals, suggesting different changes in the control mechanisms. Although understanding these changes requires further research, potential causes might be structural deteriorations leading to less efficient (intra- and interhemispheric) networks because of MCI, or an inability to appropriately divert the focus of attention.

Arterial stiffness mediates the association between age and processing speed at low levels of microvascular function in humans across the adult lifespan.

The function of micro- and macrovessels within the peripheral vasculature has been identified as a target for the investigation of potential cardiovascular-based promoters of cognitive decline. However, little remains known regarding the interaction of the micro- and macrovasculature as it relates to cognitive function, especially in cognitively healthy individuals. Therefore, our purpose was to unravel peripheral factors that contribute to the association between age and processing speed. Ninety-nine individuals (51 men, 48 women) across the adult life span (19-81 yr) were used for analysis. Arterial stiffness was quantified as carotid-femoral pulse-wave velocity (cfPWV) and near-infrared spectroscopy assessed maximal tissue oxygenation (Sto2max) following a period of ischemia. Processing speed was evaluated with Trail Making Test (TMT) Parts A and B. Measures of central (cPP) and peripheral pulse pressure (pPP) were also collected. Moderated mediation analyses were conducted to determine contributions to the age and processing speed relation, and first-order partial correlations were used to assess associations while controlling for the linear effects of age. A P ≤ 0.05 was considered statistically significant. At low levels of Sto2max, there was a significant positive (b = 1.92; P = 0.005) effect of cfPWV on time to completion on TMT part A. In addition, cPP (P = 0.028) and pPP (P = 0.027) remained significantly related to part A when controlling for age. These results suggested that the peripheral microvasculature may be a valuable target for delaying cognitive decline, especially in currently cognitively healthy individuals. Furthermore, we reinforced current evidence that pulse pressure is a key endpoint for trials aimed at preventing or delaying the onset of cognitive decline.NEW & NOTEWORTHY Arterial stiffness partially mediates the association between age and processing speed in the presence of low microvascular function, as demarcated by maximum tissue oxygenation following ischemia. Central and peripheral pulse pressure remained associated with processing speed even after controlling for age. Our findings were derived from a sample that was determined to be cognitively healthy, which highlights the potential for these outcomes to be considered during trials aimed at the prevention of cognitive decline.

Multiomic analyses suggest a divergent aging trajectory in dementia

AbstractBackgroundAging is the main risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD) and other forms of dementia. Both aging and dementia have been shown to leave a molecular signature in the plasma proteome. Understanding how the Dementia Plasma Proteome (DPP) diverges from the Aging Plasma Proteome may provide insights in pathological changes in the brains of dementia patients, or resilience mechanisms in the brain of cognitive healthy individuals. Here, we provide a more detailed overview on the aging trajectories of the DPP across ‘normal agers’ and dementia patients using a multiomic analysis approach.MethodUsing publicly available datasets such as the Human Protein Atlas, GTEx, and the Aging, Dementia and TBI study, we aim to link changes observed in the plasma to age‐associated changes in the brain and AD pathology. For this, we used publicly available databases. Using immunohistochemistry, we attempt to validate our findings in brain tissue.ResultWe show that differences in expression levels of proteins belonging to the DPP (Dementia Proteins) between non‐demented controls and demented cases are positively associated to previously identified aging associations. Furthermore, we show that Dementia Proteins are preferentially expressed in the brain and among multiple brain cell types, such as neurons, oligodendrocyte precursor cells and astrocytes. Expression trajectories during aging of brain‐expressed Dementia Proteins in the healthy brain appear largely similar as identified in the aging plasma proteome. However, we identified several proteins displaying differential aging trajectories in the brain of demented patients. Lastly, we present how these altered aging trajectories associate to several pathological measures, such as levels of Tau and Amyloid beta.ConclusionThese results suggest differences in aging trajectories between non‐demented controls and dementia patients, which may be reflected in both the plasma and in brains of dementia patients. Together, these results may provide novel insights in proteins associated with dementia‐associated pathology and their contributions to the disease progression. Future studies are needed to further validate these findings and to discover the underlying mechanisms.

P101 Brain Amyloid Burden and Autobiographical Memory in Obstructive Sleep Apnoea: A Cross-sectional Study.

Abstract Introduction Emerging literature reports an increased risk of Alzheimer’s disease in individuals with obstructive sleep apnoea (OSA). Established characteristics of Alzheimer’s disease include increased brain amyloid burden and impairment to episodic and autobiographical memory. Investigating these constructs in individuals with clinically confirmed OSA will contribute to understanding of OSA and neuronal implications. Aim The aim of the study was to explore the relationship between brain amyloid burden and autobiographical memory in cognitively-healthy individuals with OSA. Methods Thirty-four participants with OSA (mean age=57.7, SD=8.5, 19 males), and 12 controls (mean age=57.1, SD=8.1, 6 males) participated in the study. Participants underwent a 11C-PiB positron emission tomography (PET) scan to quantify amyloid burden, and an assessment of autobiographical memory. Brain amyloid burden was quantified using the standardised uptake value ratio (SUVR), and the Autobiographical Memory Test (AMT) was used to assess the ability of participants to recall specific memories from their life. Results Individuals with OSA recalled significantly fewer specific autobiographical memories (M=6.66, SD=2.91) compared to controls (M=10.25, SD=2.09, t(45)=-3.930, p<.001). There was no significant difference in SUVR between groups, t(44)=1.465, p=.150. Recall of non-specific memories was significantly positively correlated with SUVR, r=.331, p=.026. Discussion Levels of brain amyloid burden did not differ significantly between groups however the results support existing literature suggesting amyloid burden is associated with autobiographical memory in individuals with OSA. Longitudinal studies investigating the trajectory of these constructs in the context of disease development should be conducted to further explore the impacts of OSA.

Reference Data for Attentional, Executive, Linguistic, and Visual Processing Tests Obtained from Cognitively Healthy Individuals with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

Conventional neuropsychological norms likely include cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD) pathology (amyloid-β, tau, and neurodegeneration) since they are based on cohorts without AD biomarkers data. Due to this limitation, population-based norms would lack sensitivity for detecting subtle cognitive decline due to AD, the transitional stage between healthy cognition and mild cognitive impairment. We have recently published norms for memory tests in individuals with normal cerebrospinal fluid (CSF) AD biomarker levels. The aim of the present study was to provide further AD biomarker-based cognitive references covering attentional, executive function, linguistic, and visual processing tests. We analyzed 248 CU individuals aged between 50-70 years old with normal CSF Aβ, p-tau, and neurodegeneration (t-tau) biomarker levels. The tests included were the Trail Making Test (TMT), Semantic Fluency Test, Digit and Symbol Span, Coding, Matrix Reasoning, Judgement of Line Orientation and Visual Puzzles. Normative data were developed based on regression models adjusted for age, education, and sex when needed. We present equations to calculate z-scores, the corresponding normative percentile tables, and online calculators. Age, education, and sex were associated with performance in all tests, except education for the TMT-A, and sex for the TMT-B, Coding, and Semantic Fluency. Cut-offs derived from the current biomarker-based reference data were higher and more sensitive than standard norms. We developed reference data obtained from individuals with evidence of non-pathologic AD biomarker levels that may improve the objective characterization of subtle cognitive decline in preclinical AD.

Relationship between Cognitive Decline and Daily Life Gait among Elderly People Living in the Community: A Preliminary Report

Introduction: Early detection and intervention are important to prevent dementia. Gait parameters have been recognized as a potentially easy screening tool for mild cognitive impairment (MCI); however, differences in gait parameters between cognitive healthy individuals (CHI) and MCI are small. Daily life gait change may be used to detect cognitive decline earlier. In the present study, we aimed to clarify the relationship between cognitive decline and daily life gait. Methods: We performed 5-Cog function tests and daily life and laboratory-based gait assessments on 155 community-dwelling elderly people (75.5 ± 5.4 years old). Daily life gait was measured for 6 days using an iPod-touch with an accelerometer. Laboratory-based 10-m gait (fast pace) was measured using an electronic portable walkway. Results: The subjects consisted of 98 CHI (63.2%) and 57 cognitive decline individuals (CDI; 36.8%). Daily life maximum gait velocity in the CDI group (113.7 [97.0–128.5] cm/s) was significantly slower than that in the CHI group (121.2 [105.8–134.3] cm/s) (p = 0.032). In the laboratory-based gait, the stride length variability in the CDI group (2.6 [1.8–4.1]) was significantly higher than that in the CHI group (1.8 [1.2–2.7]) (p < 0.001). The maximum gait velocity in daily life gait was weakly but significantly correlated with stride length variability in laboratory-based gait (ρ = −0.260, p = 0.001). Conclusion: We found an association between cognitive decline and slower daily life gait velocity among community-dwelling elderly people.

Vitamin D Concentration and Motoric Cognitive Risk in Older Adults: Results from the Gait and Alzheimer Interactions Tracking (GAIT) Cohort.

Background. Motoric Cognitive Risk (MCR) syndrome, which combines subjective memory complaint (SMC) and slower gait speed, is a newly-described predementia stage. Based on the involvement of vitamin D in the biology of both gait and cognition, we hypothesized that nondemented individuals with MCR would exhibit hypovitaminosis D more often compared to Cognitively Healthy Individuals (CHI). The objective of this cross-sectional analysis was to determine whether hypovitaminosis D was associated with MCR. Methods. Participants without dementia from the GAIT (Gait and Alzheimer Interactions Tracking) cohort study were classified into MCR or Cognitively Healthy Individuals (CHI) groups. Hypovitaminosis D was defined as the lowest quartile of serum 25-hydroxyvitamin D (25OHD) concentration compared to the other three combined. Age, sex, body mass index (BMI), the Frontal Assessment Battery (FAB) score, the Mini-Mental Short Examination (MMSE) score, education level, use of psychoactive drugs, and the number of chronic diseases were used as covariates. Results. Among 244 nondemented and nonMCInonMCR participants from the GAIT cohort (mean age 71.4 ± 3.7 years, 40.6% women), 66 participants were classified as MCR (36.9%) and 178 as CHI (63.1%). The lowest quartile of 25OHD concentration was directly associated with MCR (unadjusted OR = 2.85, p = 0.003) even after adjustment for studied potential confounders (fully adjusted OR = 2.61, p = 0.025). The BMI (adjusted OR = 6.65, p < 0.001), MMSE score (adjusted OR = 0.74, p = 0.009), FAB score (adjusted OR = 0.51, p < 0.001), number of chronic diseases (adjusted OR = 1.29, p = 0.043) and use of psychoactive drugs (adjusted OR = 2.55, p = 0.044) were also associated with MCR. Conclusions. Hypovitaminosis D was associated with MCR in older community-dwellers without dementia.

Finger Tapping as a Biomarker to Classify Cognitive Status in 80+-Year-Olds.

This study examined the association between finger tapping and cognitive function in a group of 225 elderly participants (116 males; age 79–92 years; M = 82.5; SD = 2.4). Finger tapping was assessed in two conditions: self-selected pace and fast pace. Based on cognitive assessments, including the MoCA and CERA-NP test battery, participants were classified as cognitively healthy individuals (CHI), participants with mild cognitive impairments (MCI), and those with possible MCI (pMCI). Results of the analyses show significant differences between groups, sex and the group × sex interaction in four parameters for the self-selected pace condition and eight parameters for the fast pace condition. These parameters were used for classification by means of linear discriminant analysis (LDA). The first LDA component showed significant differences between CHI and pMCI and between CHI and MCI. Furthermore, the second LDA component showed significant differences between CHI and pMCI as well as between pMCI and MCI. Nevertheless, the algorithm correctly classified only 50% of participants, regardless of group, suggesting that tapping parameters are only partially useful for classification in early stages of dementia. We discuss these findings in terms of the diadochokinetic nature of finger tapping as associated with the age-related degeneration of cortical and subcortical motor areas.

Normative data for the Spanish version of the California Verbal Learning Test (TAVEC) from older adults.

The aim of this study was to establish normative data for the Spanish version of the California Verbal Learning Test, the Test de Aprendizaje Verbal España-Complutense (TAVEC). Through different subtests, the TAVEC allows verbal learning and episodic memory to be evaluated, an assessment that was carried out on a sample of 382 cognitive healthy Spanish individuals aged 60-90 years old. Unlike the participant's educational level, their age and sex significantly influenced performance in the TAVEC. We provide tables that allow the scaled scores obtained with this test to be adjusted for age and other tables with the relevant adjustments for sex. The normative data obtained in this study will help more precisely interpret the performance of older Spanish adults in the TAVEC, enhancing the utility of this neuropsychological test to evaluate verbal learning and episodic memory in clinical settings and in relation to healthy aging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associations between gait speed andbrain structure in amnestic mild cognitive impairment: a quantitative neuroimaging study.

Patients with amnestic mild cognitive impairment (aMCI) present gait disturbances including slower speed and higher variability when compared to cognitively healthy individuals (CHI). Brain neuroimaging could explore higher levels of motor control. Our purpose was to look for an association between morphometrics and gait parameters in each group. We hypothesized that the relation between morphological cerebral alteration and gait speed are different following the group. Fifty-three participants (30 with aMCI and 23 CHI) were recruited in this French cross-sectional study (mean 72 ± 5years, 38% female). Gait speed and gait variability (coefficients of variation of stride time (STV) and stride length (SLV)) were measured using GAITrite® system. CAT12 software was used to analyse volume and surface morphometry like gray matter volume (GMV) and cortical thickness (CT). Age, gender and education level were used as potential cofounders. aMCI had slower gait speed and higher STV when compared to CHI. In aMCI the full adjusted linear regression model showed that lower gait speed was associated with decreased GMV and lower CT in bilateral superior temporal gyri (p < 0.36). In CHI, no association was found between gait speed and brain structure. Higher SLV was correlated with reduced GMV in spread regions (p < 0.05) and thinner cortex in the middle right frontal gyrus (p = 0.001) in aMCI. In CHI, higher SLV was associated with reduced GMV in 1 cluster: the left lingual (p = 0.041). These findings indicate that lower gait speed is associated with specific brain structural changes as reduced GMV and CT during aMCI.

Occupation-related effects on motor cortex thickness among older, cognitive healthy individuals

Both, decline of sensorimotor functions and cortical thickness are known processes in healthy aging. Physical activity has been suggested to enhance the execution of daily routine activities and to extend the time of functional independence in advanced age. We hypothesized that cortical thickness of motor areas in retired individuals could be related to physical demands of the profession carried out during working life. Depending on their former occupations, 69 cognitively healthy individuals (range 70–85 years) were divided into higher and lower physically complex occupations (HPCO n = 27 and LPCO n = 42) according to the international standard classification of occupations (ISCO-08). Participants underwent a high-resolution 3T T1-weighted MRI scan. Surface-based analysis revealed higher cortical thickness in the left precentral (P = 0.001) and postcentral gyrus (P < 0.001) and right postcentral gyrus (P = 0.001) for the HPCO relative to the LPCO group (corrected for multiple comparisons, sex, age and leisure activities in the past 20 years). Physical leisure activities associated with exertion were positively correlated with cortical thickness in the left pre- and postcentral gyrus (P = 0.037) of the LPCO group. Time since retirement was negatively associated with cortical thickness in the left postcentral gyrus (P = 0.004) of the HPCO group. Executing a higher physically complex occupation before retirement was related to relative higher cortical thickness in the primary motor and somatosensory cortex in later life, supporting the hypothesis that physical activity contributes to neural reserve in these regions. However, these benefits appear to vanish when physical activity is reduced due to retirement.

Face–Name Associative Memory Performance Among Cognitively Healthy Individuals, Individuals With Subjective Memory Complaints, and Patients With a Diagnosis of aMCI

Face–Name Associative Memory Performance Among Cognitively Healthy Individuals, Individuals With Subjective Memory Complaints, and Patients With a Diagnosis of aMCI

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.

Gait Parameter Estimation of Elderly People using 3D Human Pose Estimation in Early Detection of Dementia.

Early detection of dementia is becoming increasingly important as it plays a crucial role in handling the patients and offering better treatment. Many of the recent studies concluded a tight relationship between dementia and gait disorders. For this purpose, identification of gait abnormalities is key factor. Novel technologies provide many options such as wearable and non-wearable approaches for analysis of gait. As the occurrence of dementia is more prominent in elderly people, wearable technology is considered out of scope for this work. The gait data of several elderly people over 80 years is acquired over certain intervals during the scope of the project. The elderly people are classified into three study groups namely cognitively healthy individuals (CHI), subjectively cognitively impaired persons (SCI) and possible mildly cognitively impaired persons due to inconclusive test results (pMCI) based on their cognitive status. The gait data is acquired using Kinect sensor. The acquired data consists of both RGB image sequences and depth data of the test persons. 3D human pose estimation is performed on this gait data and gait analysis is done. The transformations in the gait cycles are observed and the health condition of the individual is analyzed. From the analysis, the patterns in the gait abnormalities are correlated with the above-mentioned classification and are used in the detection of dementia in advance. The obtained results look promising and further analysis of gait parameters is under progress.

Sensor-based systems for early detection of dementia (SENDA): a study protocol for a prospective cohort sequential study

BackgroundDementia and cognitive decline are serious social and economic burdens. An increase in the population of older people, as well as longer lifespans mean that numbers of dementia cases are exponentially rising. Neuropathological changes associated with dementia are thought to appear before the clinical manifestation of cognitive symptoms, i.e., memory impairments. Further, some older adults (OA) experience cognitive decline before it can be objectively diagnosed. For optimal care of these patients, it is necessary to detect cognitive decline and dementia at an early stage. In this vein, motor, sensory, and neurophysiological declines could be promising factors if found to be present before the onset of cognitive impairment. Hence, the objective of the SENDA study is to develop a multi-dimensional sensor-based instrument that allows early detection of cognitive decline or dementia in OA with the help of cognitive, sensory, motor, and neurophysiological parameters before its clinical manifestation.Methods/designIn the cohort sequential study, participants are assigned to one of three study groups depending on their cognitive status: 1. cognitively healthy individuals (CHI), 2. subjectively cognitively impaired persons (SCI), or 3. (possible) mildly cognitively impaired persons (pMCI, MCI). All groups take part in the same cognitive (e.g., executive function tests), motor (e.g., gait analyses, balance tests), sensory (e.g., vibration perception threshold test, proprioception tests), and neurophysiological (e.g., electroencephalograms) measurements. Depending on the time at which participants are included into the study, all measurements are repeated up to four times in intervals of 8 months within 3 years to identify associations with cognitive changes over time.DiscussionThis study aims to detect possible motor, sensory, neurophysiological, and cognitive predictors to develop an early screening tool for dementia and its pre-stages in OA. Thus, affected persons could receive optimal health care at an earlier time point to maintain their health resources.Trial statusThe study is ongoing. The recruitment of participants will be continued until May 2020.

A machine learning-based linguistic battery for diagnosing mild cognitive impairment due to Alzheimer's disease.

There is a limited evaluation of an independent linguistic battery for early diagnosis of Mild Cognitive Impairment due to Alzheimer’s disease (MCI-AD). We hypothesized that an independent linguistic battery comprising of only the language components or subtests of popular test batteries could give a better clinical diagnosis for MCI-AD compared to using an exhaustive battery of tests. As such, we combined multiple clinical datasets and performed Exploratory Factor Analysis (EFA) to extract the underlying linguistic constructs from a combination of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD), Wechsler Memory Scale (WMS) Logical Memory (LM) I and II, and the Boston Naming Test. Furthermore, we trained a machine-learning algorithm that validates the clinical relevance of the independent linguistic battery for differentiating between patients with MCI-AD and cognitive healthy control individuals. Our EFA identified ten linguistic variables with distinct underlying linguistic constructs that show Cronbach’s alpha of 0.74 on the MCI-AD group and 0.87 on the healthy control group. Our machine learning evaluation showed a robust AUC of 0.97 when controlled for age, sex, race, and education, and a clinically reliable AUC of 0.88 without controlling for age, sex, race, and education. Overall, the linguistic battery showed a better diagnostic result compared to the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and a combination of MMSE and CDR.

Brain Gray Matter Volume Associations With Abnormal Gait Imagery in Patients With Mild Cognitive Impairment: Results of a Cross-Sectional Study.

Individuals with mild cognitive impairment (MCI) have worse gait performance compared to cognitive healthy individuals (CHI). The discrepancy between imagined and performed timed up and go test (TUG), known as the TUG delta time, is a marker of brain gait control impairment in individuals with MCI. The study aims to examine the association between the TUG delta time and brain gray matter (GM) volumes in CHI and individuals with MCI. A total of 326 participants, 156 CHI and 170 MCI, with TUG delta time and a brain T1-weighted magnetic resonance imaging (MRI) were selected in this cross-sectional study. Individuals with MCI were older and had greater (i.e., worst performance) performed TUG and TUG delta time compared to CHI. The GM volume association with TUG delta time was examined in CHI and MCI assuming that increased TUG delta time would be associated with locally decreased GM volumes. No significant association was found in CHI, whereas TUG delta time was negatively associated with the GM volume of the right medial temporal lobe in individuals with MCI.

Default mode network and the timed up and go in MCI: A structural covariance analysis.

The timed up and go (TUG) is a test used to assess mobility in older adults and patients with neurological conditions. This study aims to compare brain gray matter (GM) correlates and structural covariance networks associated with the TUG time in cognitively healthy individuals (CHI) and in patients with mild cognitive impairment (MCI). The TUG time was measured in 326 non-demented older community-dwellers (age 71.3 ± 4.5; 42% female) - 156 CHI and 170 MCI. GM covariance networks were computed using voxel-based morphometry with the main neural correlates of TUG for each group as seed regions. Increased TUG time (i.e., poor performance) was associated with distinct brain volume reductions between CHI and MCI. The covariance analysis showed cortical regions involving the default mode network in CHI and bilateral cerebellar regions in MCI. GM networks associated with the TUG vary between CHI and MCI, suggesting distinct brain control for locomotion between CHI and MCI patients.

Levels of islet amyloid polypeptide in cerebrospinal fluid and plasma from patients with Alzheimer's disease.

The biologically active pancreatic hormone peptide islet amyloid polypeptide (IAPP) regulates brain functions such as appetite and cognition. It also plays a role in clearance of amyloid beta (Aβ), a peptide implicated in the dementia disorder Alzheimer’s disease (AD). If IAPP becomes modified, it loses its biological activity and starts to aggregate. Such aggregations have been found in the AD brain and decreased plasma levels of the unmodified IAPP (uIAPP) have been shown in the same patients. In the current study, we analyze levels of uIAPP and total IAPP (unmodified and modified) in cerebrospinal fluid (CSF) to investigate its potential as a biomarker for AD. We found no differences in neither CSF nor plasma levels of uIAPP or total IAPP in AD patients compared to cognitive healthy individuals (NC). The levels of uIAPP in CSF of NC were positively correlated with uIAPP in plasma, Q-albumin and albumin levels in CSF, but negatively correlated with CSF levels of t-tau and p-tau. These findings were not seen in AD patients. Levels of total CSF IAPP correlated positively with total Q-albumin and albumin levels in CSF in both AD and NC. In addition, total plasma IAPP correlated positively with CSF t-tau and p-tau in NC and negatively with CSF Aβ42 in AD patients. To conclude, our studies did not find evidence supporting the use of CSF IAPP as an AD biomarker. However, our findings, indicating a compromised translocation of uIAPP in and out of the brain in AD patients as well as the correlations between total plasma IAPP and AD biomarkers, encourage further research on the role for IAPP in AD.

Brain gray matter volume associations with gait speed and related structural covariance networks in cognitively healthy individuals and in patients with mild cognitive impairment: A cross-sectional study.

Gait speed is slower in patients with mild cognitive impairment (MCI) compared to cognitively healthy individuals (CHI). We examined the patterns of brain gray matter (GM) volume association and covariance with gait speed in CHI and in patients with MCI. A total of 96 CHI and 99 patients with MCI were recruited in this cross-sectional study. Brain GM volumes measured with voxel-based morphometry and self-paced gait speed were used as outcomes. The right middle frontal and precentral gyri volumes were positively associated with gait speed in CHI and covariated with frontal cortex. Striatum (i.e. left putamen and bilateral caudate nuclei) volumes were positively associated with gait speed in patients with MCI and covariated with striatal structures. Two different patterns of brain GM volume association and covariance with gait speed were found and involving frontal cortex in CHI and the striatum in patients with MCI.