Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment
Breton M. AskenLawren VandeVredeJulio C. RojasCorrina FonsecaAdam M. StaffaroniFanny M. ElahiCutter A. LindberghAlexandra C. AppleMichelle YouSophia Weiner‐LightNivetha BrathabanNicole FernandesAdam L. BoxerBruce L. MillerHowie RosenJoel H. KramerKaitlin B. Casaletto
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Abstract Objective: There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia. Methods: We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates. Results: Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP. Conclusions: Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.Keywords:
Neuropsychological Assessment
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Executive dysfunction
Voxel-based morphometry
Cognitive impairment is common in multiple sclerosis (MS), with up to 65% of patients exhibiting some type of neuropsychological dysfunction. The cognitive domains most affected by MS are learning and memory, attention, information processing, visuospatial abilities, and executive functioning. It is difficult to detect cognitive dysfunction in patients with MS during routine neurologic examinations because conventional measures of neurologic disability are not sensitive enough to detect cognitive impairment. Furthermore, cognitive dysfunction is only weakly correlated with the type of MS, disease duration, or physical disability. However, brain imaging studies show that a relatively strong correlation exists between cognitive dysfunction and overall lesion burden and brain atrophy in MS. This paper reviews the natural history of cognitive dysfunction, areas of cognition affected, the correlation between MRI measures and cognitive dysfunction, issues related to neuropsychological assessment, and treatment of cognitive impairment with disease-modifying MS drugs.
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<i>Objectives:</i> Vascular pathology is associated with reduced performance on neuropsychological tests, particularly in older adults. A likely explanation involves a disruption in the blood brain barrier (BBB). Work from clinical samples show alterations in BBB function is associated with cognitive dysfunction on testing, though no study has examined this possibility in healthy older adults. <i>Materials and Methods:</i> 35 older adults, without significant neurological or psychiatric history, underwent fasting blood draw and neuropsychological testing. Serum levels of S100β were quantified to provide a measure of BBB function. <i>Results:</i> Partial correlations showed S100β levels were inversely related to performance in multiple cognitive domains, including memory (r = 0.43, p = 0.02), psychomotor speed and visual attention (r = 0.37, p = 0.05), and working memory (r = –0.48, p = 0.008). <i>Conclusions:</i> Findings indicate that increased S100β levels are associated with poorer cognitive function in neurologically healthy older adults, implicating BBB function in age-related cognitive decline. Further work is needed to clarify possible mechanisms, particularly longitudinal studies that involve neuroimaging.
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Neuropsychology contributes significantly to the diagnosis of dementia. Cognitive deficits can be detected several years prior to the clinical diagnosis of dementia. This review focuses on the diagnosis of dementia, using neuropsycholoical assessment and early neuropsychological characteristics of different dementia syndromes.
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Objective: To compare the rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (VaD) (n = 79), AD (n = 113), or stroke without dementia (SWD) (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations. Methods: Study patients were diagnosed using established criteria for dementia and were administered cognitive screening, functional screening, and neuropsychological measures. Baseline dementia severity was rated using the Clinical Dementia Rating Scale. Random effects modeling was used to examine rates of decline and to compare the rates of decline in the three groups. Results: Both patients with VaD and those with AD showed significant cognitive and functional decline during follow-up; patients with VaD declined at a slower rate than patients with AD; and patients diagnosed with SWD at baseline did not show cognitive or functional decline during follow-up. Conclusions: Patients with VaD decline at a slower rate than patients with AD. Patients who do not meet criteria for dementia soon after stroke may not be at high risk for developing dementia. Future studies are needed to follow VaD patients with longitudinal, specialized MR protocols, concurrent neuropsychological examinations, and neuropathologic examination to determine possible neuroimaging predictors of progressive cognitive and functional decline and to assess the contribution of Alzheimer's pathology to decline in patients diagnosed with VaD.
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Although cognitive impairment is one of the common problems among many patients with epilepsy, it is still not well defined in childhood absence epilepsy. Here, the authors assess the cognitive and executive function in childhood absence epilepsy in a group of school‐age children in Egypt. They discuss the need for early identification of neuropsychological dysfunction so that appropriate management can be implemented.
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Consumption of large amounts of alcohol is known to have negative effects, but consumption in smaller amounts may be protective. The effect of alcohol may be greater in the elderly than in younger adults, particularly with regard to cognition. However, the drinking pattern that will provide optimal protection against dementia and cognitive decline in the elderly has not been systematically investigated. The present paper is a critical review of research on the effect of alcohol on cognitive function and dementia in the elderly. Studies published from 1971 to 2011 related to alcohol and cognition in the elderly were reviewed using a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect. Longitudinal and brain imaging studies in the elderly show that excessive alcohol consumption may increase the risk of cognitive dysfunction and dementia, but low to moderate alcohol intake may protect against cognitive decline and dementia and provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol consumption in the elderly protects against cognitive decline and dementia exists; however, because of varying methodology and a lack of standardized definitions, these findings should be interpreted with caution. It is important to conduct more, well-designed studies to identify the alcohol drinking pattern that will optimally protect the elderly against cognitive decline and dementia.
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Objective: Although it is known that accelerated decline in cognitive function precedes dementia onset by several years among demented subjects, enough knowledge has not been obtained about cognitive decline among subjects without dementia. We investigated age, gender, education, radiation and birth cohort effects in global cognition decline among dementia-free subjects. Method: This study examined cognitive decline among about 1700 dementia-free subjects between 1992 and 2011 through biennial medical check-up. Participants were from the Adult Health Study (AHS), consisting of atomic bomb survivors and their controls, aged 60 years or older at study-start (1992). We evaluated cognitive performance with the Cognitive Abilities Screening Instrument (CASI). Results: Averaging 8.6 years of follow-up, many subjects experienced cognitive decline. Older ages were related to both decreased initial levels and faster rates of decline in cognitive function. More years of formal education associated with higher initial levels, but was not found to affect cognitive decline over time. Additionally, education had a stronger positive effect on initial levels of women than that of men. Finally, radiation was not found to affect cognitive function at baseline or over time. Conclusions: The longitudinal study of the AHS provides a better understanding of the decline of cognition among dementia-free subjects. The results are also useful as reference at dementia screening.
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ABSTRACT It has become standard practice to base the diagnosis of dementia on the combination of neuropsychological and non-behavioral findings. The present article provides a short, clinically oriented synopsis of the targets, investigational procedures, and difficulties of the modern neuropsychological approach to the diagnosis of dementia. Over the years, neuropsychology has developed assessment tools to evaluate the cognitive and behavioral abnormalities of many dementias. Validated tests of memory, language, executive, and other cognitive functions are used to screen for dementia and identifying certain dementia profiles. Behavioral assessment procedures are available for non-cognitive neurodegenerative alterations. At present, problems arise mainly with the behavioral heterogeneity of certain dementia syndromes. Especially problamatic are discrimination of age-associated or mild cognitive impairments from incipient dementia and the impact of psychiatric symptoms on cognitive functions. It is concluded that neuropsychology offers a valuable contribution to the diagnosis and differential diagnosis of dementia.
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