Dataset Information

Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort.

ABSTRACT: BACKGROUND:Gait analysis with accelerometers is a relatively inexpensive and easy to use method to potentially support clinical diagnoses of Alzheimer's disease and other dementias. It is not clear, however, which gait features are most informative and how these measures relate to Alzheimer's disease pathology. OBJECTIVE:In this study, we tested if calculated features of gait 1) differ between cognitively normal subjects (CN), mild cognitive impairment (MCI) patients, and dementia patients, 2) are correlated with cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, and 3) predict cognitive decline. METHODS:Gait was measured using tri-axial accelerometers attached to the fifth lumbar vertebra (L5) in 58 CN, 58 MCI, and 26 dementia participants, while performing a walk and dual task. Ten gait features were calculated from the vertical L5 accelerations, following principal component analysis clustered in four domains, namely pace, rhythm, time variability, and length variability. Cognitive decline over time was measured using MMSE, and CSF biomarkers were available in a sub-group. RESULTS:Linear mixed models showed that dementia patients had lower pace scores than MCI patients and CN subjects (p?

SUBMITTER: Muurling M

PROVIDER: S-EPMC7505008 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort.

Muurling Marijn M Rhodius-Meester Hanneke F M HFM Pärkkä Juha J van Gils Mark M Frederiksen Kristian S KS Bruun Marie M Hasselbalch Steen G SG Soininen Hilkka H Herukka Sanna-Kaisa SK Hallikainen Merja M Teunissen Charlotte E CE Visser Pieter Jelle PJ Scheltens Philip P van der Flier Wiesje M WM Mattila Jussi J Lötjönen Jyrki J de Boer Casper C

Journal of Alzheimer's disease : JAD 20200101 3

<h4>Background</h4>Gait analysis with accelerometers is a relatively inexpensive and easy to use method to potentially support clinical diagnoses of Alzheimer's disease and other dementias. It is not clear, however, which gait features are most informative and how these measures relate to Alzheimer's disease pathology.<h4>Objective</h4>In this study, we tested if calculated features of gait 1) differ between cognitively normal subjects (CN), mild cognitive impairment (MCI) patients, and dementia ...[more]

PMID: 32597806

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Project description:Importance:Prior evidence suggests that racial differences exist in tau biomarkers in mild cognitive impairment (MCI) and Alzheimer disease (AD). Whether this reported disparity is associated with a differential level of neurodegeneration and disease stage or with underlying mechanisms separate from amyloid or tau is unclear. Objectives:To compare cerebrospinal fluid (CSF) biomarkers in African American and white individuals with normal cognition and MCI, to estimate race-based cutoffs for these biomarkers that maximize diagnostic discrimination between normal cognition and MCI, and to study the association of demographic characteristics, cognitive performance, and common vascular risk factors with these differences. Design, Setting, and Participants:This case-control study conducted from March 1, 2016, through January 31, 2019, included participants in the Brain Stress Hypertension and Aging Research Program cohort undergoing baseline assessment. Participants were 50 years or older and recruited from the Atlanta, Georgia, area. Exposures:Self-reported race and cognitive status categorized using modified Petersen criteria and clinical consensus diagnosis. Main Outcomes and Measures:Levels of ?-amyloid 1-42 (A?1-42), tau, and phosphorylated tau 181 (pTau181), the ratio of tau or pTau181 to A?1-42, and hippocampal volume on magnetic resonance imaging of the brain. Results:Data from 362 study participants were analyzed (mean [SD] age, 65.6 [7.9] years), of whom 152 (42.0%) were African American, 230 (63.5%) were women, and 189 (52.2%) had MCI. After adjustment for demographic characteristics and cognitive performance, lower mean (SE) levels were observed in African American vs white individuals with MCI for tau (52.40 [5.90] vs 78.98 [5.02] pg/mL; P?=?.001) and pTau181 (15.42 [2.06] vs 25.24 [1.75] pg/mL; P?=?.001) and a lower pTau181 to A?1-42 ratio (0.07 [0.02] vs 0.14 [0.01]; P?=?.003). There were no racial differences in the normal cognition group or in hippocampal volumes in the MCI group. Cutoffs for CSF biomarkers were higher for A?1-42 in African American relative to white individuals (208 [95% CI, 126-321] vs 197 [95% CI, 183-245] pg/mL) and lower for tau (51 [95% CI, 31-59] vs 59 [95% CI, 56-92] pg/mL) and pTau181 (12 [95% CI, 12-19] vs 20 [95% CI, 12-27] pg/mL) levels. Cutoffs for the pTau181 to A?1-42 ratio were 0.05 (95% CI, 0.03-0.12) for African American participants and 0.05 (95% CI, 0.05-0.13) for white participants. Conclusions and Relevance:This study found that African American individuals had lower levels of tau-based biomarkers that were not likely explained by the degree of disease stage or neurodegeneration reflected by hippocampal volumes. This study suggests that race is an important factor when interpreting CSF biomarkers, especially in the clinical diagnosis of prodromal AD. It appears that using the pTau181 to A?1-42 ratio may ameliorate these differences.

Project description:ObjectiveTo compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI).DesignRandomized controlled trial.SettingVeterans Affairs Medical Center clinical research unit.ParticipantsForty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years).InterventionParticipants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet.Main outcome measuresThe CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.ResultsFor the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet.ConclusionOur results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.

Project description:BackgroundVisinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer's disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD.MethodsWe stratified 121 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD. Analysis of covariance (ANOVA) and chi-square analyses, Spearman correlation, and logistic regression models were performed to test the demographic, associations between biomarkers, and diagnostic accuracies, respectively. Linear mixed-effects models were used to evaluate the effects of CSF amyloid-? (A?) on above biomarkers within diagnostic groups, the combination of diagnostic group and A? status as predictor, and CSF biomarkers as predictors of AD features, including cognition measured by Mini-Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI).ResultsP-tau, VILIP-1, and YKL-40 were all predictors of AD diagnosis, but combinations of biomarkers did not improve the diagnostic accuracy (AUC 0.924 for p-tau, VILIP-1, and YKL-40) compared to p-tau (AUC 0.922). P-tau and VILIP-1 were highly correlated (r?=?0.639, p?<?0.001) and strongly associated with A? pathology across clinical stages of AD, while YKL-40 was correlated with A? pathology in CN and AD groups. VILIP-1 was associated with acceleration of cognitive decline, hippocampal atrophy, and expansion of ventricles in longitudinal analyses. YKL-40 was associated with hippocampal atrophy at baseline and follow-up, while p-tau was only associated with worsening WMH at baseline.ConclusionsCSF levels of p-tau, VILIP-1, and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD. Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration. These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD.

Dataset Information

Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort.

Publications

Gait Disturbances are Associated with Increased Cognitive Impairment and Cerebrospinal Fluid Tau Levels in a Memory Clinic Cohort.

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