scholarly journals Sensitive Measures of Cognition in Mild Cognitive Impairment

2021 ◽  
pp. 1-14
Author(s):  
Nathaniel Klooster ◽  
Stacey Humphries ◽  
Eileen Cardillo ◽  
Franziska Hartung ◽  
Long Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Semantic Memory ◽  
Medial Temporal Lobe ◽  
Figurative Language ◽  
Neurofibrillary Tangle ◽  
Experimental Tests ◽  
Perirhinal Cortex ◽  
Cognitive Change ◽  
Preclinical Ad

Background: Sensitive measures of cognition are needed in preclinical and prodromal Alzheimer’s disease (AD) to track cognitive change and evaluate potential interventions. Neurofibrillary tangle pathology in AD is first observed in Brodmann Area 35 (BA35), the medial portion of the perirhinal cortex. The importance of the perirhinal cortex for semantic memory may explain early impairments of semantics in preclinical AD. Additionally, our research has tied figurative language impairment to neurodegenerative disease. Objective: We aim to identify tasks that are sensitive to cognitive impairment in individuals with mild cognitive impairment (MCI), and that are sensitive to atrophy in BA35. Methods: Individuals with MCI and cognitively normal participants (CN) were tested on productive and receptive experimental measures of semantic memory and experimental tests of figurative language comprehension (including metaphor and verbal analogy). Performance was related to structural imaging and standard neuropsychological assessment. Results: On the experimental tests of semantics and figurative language, people with MCI performed worse than CN participants. The experimental semantic memory tasks are sensitive and specific; performance on the experimental semantic memory tasks related to medial temporal lobe structural integrity, including BA35, while standard neuropsychological assessments of semantic memory did not, demonstrating the sensitivity of these experimental measures. A visuo-spatial analogy task did not differentiate groups, confirming the specificity of semantic and figurative language tasks. Conclusion: These experimental measures appear sensitive to cognitive change and neurodegeneration early in the AD trajectory and may prove useful in tracking cognitive change in clinical trials aimed at early intervention.

scholarly journals Sensitive measures of cognition in Mild Cognitive Impairment

2020 ◽  
Author(s):  
Nathaniel Klooster ◽  
Stacey Humphries ◽  
Eileen Cardillo ◽  
Franziska Hartung ◽  
Long Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Semantic Memory ◽  
Figurative Language ◽  
Structural Integrity ◽  
Neurofibrillary Tangle ◽  
Perirhinal Cortex ◽  
Cognitive Change ◽  
Preclinical Ad ◽  
Neuropsychological Assessments

Sensitive measures of cognition are needed in preclinical and prodromal Alzheimer’s disease (AD) to track cognitive change and evaluate potential interventions. We hypothesize that measures of semantic richness and figurative language are sensitive to cognitive impairment in prodromal AD. The neurofibrillary tangle (NFT) pathology of AD is first observed in BA35, the medial portion of the perirhinal cortex. The importance of the perirhinal cortex for semantic memory may explain early impairments of semantic memory in preclinical AD. Additionally, our research has tied figurative language impairment to neurodegenerative disease. We predict that people with Mild Cognitive Impairment (MCI) will perform worse on these tasks than participants with normal cognition (CN), and task performance will relate to atrophy in Brodmann Area 35 (BA35). On productive and receptive measures of semantic memory and tests of figurative language comprehension (including metaphor and verbal analogy), CN participants performed better than people with MCI. These experimental tasks outperformed standard neuropsychological assessments in differentiating patients with MCI from CN. Performance on the semantic memory tasks related to MTL structural integrity, including BA35, while standard neuropsychological assessments of semantic memory did not, demonstrating the sensitivity of these experimental measures. A visuo-spatial analogy task did not differentiate groups, confirming the specificity of semantic and figurative language tasks. These experimental measures appear sensitive to cognitive change and neurodegeneration early in the AD trajectory and may prove useful in tracking cognitive change in clinical trials aimed at early intervention.

In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment

Neurology ◽  
2020 ◽  
Vol 95 (5) ◽  
pp. e545-e553 ◽  
Author(s):  
Heleen Vanhaute ◽  
Jenny Ceccarini ◽  
Laura Michiels ◽  
Michel Koole ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Performance ◽  
Medial Temporal Lobe ◽  
Clinical Symptoms ◽  
Neurofibrillary Tangle ◽  
Amnestic Mild Cognitive Impairment ◽  
Cross Sectional ◽  
Synaptic Density

ObjectiveTo investigate in vivo whether synaptic loss and neurofibrillary tangle load spatially overlap and correlate with clinical symptoms in patients with amnestic mild cognitive impairment (aMCI).MethodsIn this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11C-UCB-J (synaptic vesicle protein 2A), 18F-MK-6240 (tau deposition), and 11C-Pittsburgh compound B (β-amyloid) and neuropsychological assessment. Gray matter atrophy was assessed by voxel-based morphometry with T1-weighted MRIs. Voxel-wise and volume-of-interest analyses were conducted on PET data. The interrelationship of synaptic density and tau deposition was investigated. We also investigated correlations of 18F-MK-6240 and 11C-UCB-J binding with cognitive performance.ResultsCompared to controls, patients with aMCI showed a decreased 11C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%–51%, pcluster = 0.02). Increased 18F-MK6240 binding in the same region was observed (42%–44%, pcluster = 0.0003), spreading to association cortices. In the MTL, higher 18F-MK-6240 binding inversely related to lower 11C-UCB-J binding (p = 0.02, r = −0.76). Decreased performance on cognitive tests was associated with both increased 18F-MK-6240 and decreased 11C-UCB-J binding in the hippocampus (p < 0.01, r > 0.7), although in a multivariate analysis only 18F-MK-6240 binding was significantly related to cognitive performance.ConclusionsPatients with aMCI have high tau deposition and synaptic density loss mainly in key regions known to be involved in early cognitive impairment, indicating that these are interrelated in the MTL, while tau binding had already spread toward association cortices. Longitudinal data are needed to provide further insight into the temporal aspects of this relationship.

scholarly journals State of the science on mild cognitive impairment (MCI)

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Nicole D. Anderson
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Social Engagement ◽  
Medial Temporal Lobe ◽  
Healthy Aging ◽  
Cognitive Screening ◽  
Symptoms Of Depression ◽  
Preclinical Ad ◽  
Positron Emission ◽  
State Of The Science

Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects 10–15% of the population over the age of 65. The failure of drug trials in Alzheimer’s disease (AD) treatment has shifted researchers’ focus toward delaying progression from MCI to dementia, which would reduce the prevalence and costs of dementia profoundly. Diagnostic criteria for MCI increasingly emphasize the need for positive biomarkers to detect preclinical AD. The phenomenology of MCI comprises lower quality-of-life, greater symptoms of depression, and avoidant coping strategies including withdrawal from social engagement. Neurobiological features of MCI are hypoperfusion and hypometabolism in temporoparietal cortices, medial temporal lobe atrophy particularly in rhinal cortices, elevated tau and phosphorylated tau and decreased Aβ42in cerebrospinal fluid, and brain Aβ42deposition. Elevated tau can be identified in MCI, particularly in the entorhinal cortex, using positron emission tomography, and analysis of signal complexity using electroencephalography or magnetoencephalography holds promise as a biomarker. Assessment of MCI also relies on cognitive screening and neuropsychological assessment, but there is an urgent need for standardized cognitive tests to capitalize on recent discoveries in cognitive neuroscience that may lead to more sensitive measures of MCI. Cholinesterase inhibitors are frequently prescribed for MCI, despite the lack of evidence for their efficacy. Exercise and diet interventions hold promise for increasing reserve in MCI, and group psychoeducational programs teaching practical memory strategies appear effective. More work is needed to better understand the phenomenology and neurobiology of MCI, and how best to assess it and delay progression to dementia.

The Relational and Item-Specific Encoding Task in Mild Cognitive Impairment and Alzheimer Disease

2016 ◽  
Vol 42 (5-6) ◽  
pp. 265-277 ◽  
Author(s):  
Amber Sousa ◽  
Jesus J. Gomar ◽  
J. Daniel Ragland ◽  
Concepcion Conejero-Goldberg ◽  
Justin Buthorn ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Psychometric Properties ◽  
Medial Temporal Lobe ◽  
Functional Competence ◽  
Neuropsychological Measures ◽  
Receiver Operating Characteristic Curves ◽  
Preclinical Ad ◽  
Relational Encoding

Background: The Relational and Item-Specific Encoding task (RISE) measures episodic memory subcomponents, including item-specific and relational encoding of to-be-remembered stimuli. These memory components are neurobiologically relevant because they may engage distinct subregions of the medial temporal lobe, perirhinal and entorhinal cortices, parahippocampus, and hippocampus. Methods: A total of 125 participants, including 84 healthy controls (HC), 22 mild cognitive impairment-diagnosed and 19 Alzheimer disease (AD)-diagnosed participants, were administered the RISE and neuropsychological measures. Stepwise linear regressions assessed prediction of functional ability from RISE d′ measures. ANOVAs and logistic regressions determined the ability of the RISE to discriminate between the diagnostic groups. In addition, the psychometric properties of the RISE were examined. Results: RISE measures predicted diagnosis with pseudo R2 values in the range of 0.25-0.30. Receiver operating characteristic curves demonstrated adequate sensitivity and specificity with areas under the curve in the range of 0.78-0.98. Memory following relational encoding was a significant predictor of everyday functional competence. The RISE had acceptable psychometric properties, with the exception of floor effects in the AD group. Conclusion: The RISE measures significantly predicted diagnosis and predicted everyday functional competence. The RISE offers unique advantages in the assessment of HC and individuals with preclinical AD.

Brain Structural Substrates of Semantic Memory Decline in Mild Cognitive Impairment

2013 ◽  
Vol 10 (4) ◽  
pp. 373-389 ◽  
Author(s):  
Simona Gardini ◽  
Fernando Cuetos ◽  
Fabrizio Fasano ◽  
Francesca Ferrari Pellegrini ◽  
Massimo Marchi ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Semantic Memory ◽  
Memory Decline

Discriminating accuracy of medial temporal lobe volumetry and fMRI in mild cognitive impairment

Hippocampus ◽  
2009 ◽  
Vol 19 (2) ◽  
pp. 166-175 ◽  
Author(s):  
Anne M. Jauhiainen ◽  
Maija Pihlajamäki ◽  
Susanna Tervo ◽  
Eini Niskanen ◽  
Heikki Tanila ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe

scholarly journals Increased functional connectivity within medial temporal lobe in mild cognitive impairment

Hippocampus ◽  
2012 ◽  
Vol 23 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Sandhitsu R. Das ◽  
John Pluta ◽  
Lauren Mancuso ◽  
Dasha Kliot ◽  
Sylvia Orozco ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Temporal Lobe ◽  
Medial Temporal Lobe

scholarly journals Lexical semantic memory in amnestic mild cognitive impairment and mild Alzheimer's disease

2007 ◽  
Vol 65 (3a) ◽  
pp. 619-622 ◽  
Author(s):  
Marcio L.F. Balthazar ◽  
José E. Martinelli ◽  
Fernando Cendes ◽  
Benito P. Damasceno
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Semantic Memory ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Amnestic Mild Cognitive Impairment ◽  
Memory Tests ◽  
Lexical Semantic

OBJECTIVE: To study lexical semantic memory in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer's disease (AD) and normal controls. METHOD: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, and that of aMCI, on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent semantic memory tests (Boston Naming-BNT, CAMCOG Similarities item), Rey Auditory Verbal Learning Test (RAVLT), Mini-Mental Status Examination (MMSE), neuropsychological tests (counterproofs), and Cornell Scale for Depression in Dementia. Data analysis used Mann-Whitney test for intergroup comparisons and Pearson's coefficient for correlations between memory tests and counterproofs (statistical significance level was p<0.05). RESULTS: aMCI patients were similar to controls on BNT and Similarities, but worse on MMSE and RAVLT. Mild AD patients scored significantly worse than aMCI and controls on all tests. CONCLUSION: aMCI impairs episodic memory but tends to spare lexical semantic system, which can be affected in the early phase of AD.

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