Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021;82(3):1123-1136.
doi: 10.3233/JAD-201280.

Sensitive Measures of Cognition in Mild Cognitive Impairment

Nathaniel Klooster  1   2 , Stacey Humphries  1   3 , Eileen Cardillo  1   3 , Franziska Hartung  1   3 , Long Xie  4   5 , Sandhitsu Das  4 , Paul Yushkevich  4 , Arun Pilania  4   6 , Jieqiong Wang  1 , David A Wolk  1   6 , Anjan Chatterjee  1   2   3   6
Affiliations

Sensitive Measures of Cognition in Mild Cognitive Impairment

Nathaniel Klooster et al. J Alzheimers Dis. 2021.

Abstract

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.

Keywords: Alzheimer’s disease; figurative language; medial temporal lobe; mild cognitive impairment; perirhinal cortex; semantic memory.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Wolk has received grant funding from Merck, Biogen, and Avid/Eli Lilly; he has received consulting fees from GE Healthcare and Neuronix and is on a DSMB for Functional Neuromodulation.

Figures

Figure 1.
Figure 1.
Example stimuli from shape and color trials of visuospatial analogical reasoning task (VSA) and within-domain and cross-domain verbal analogical reasoning task (VGA), derived from Watson & Chatterjee (2012) and Green et al (2010), respectively.
Figure 2.
Figure 2.
Task performance (adjusted for differences in age and level of education) from participants with normal cognition (CN) and participants with Mild Cognitive Impairment (MCI). *p < 0.05. Error bars represent standard error of the mean.
Figure 3.
Figure 3.
Senses produced as a function of BA35 cortical thickness by cognitively normal participants (CN) and patients with mild cognitive impairment (MCI; β= 0.77, p < 0.05).
Figure 4.
Figure 4.
Mean word associates correctly identified as a function of BA35 cortical thickness by healthy comparison participants (CN) and patients with mild cognitive impairment (MCI; β = 0.191, p < 0.05) on the Word Associates Test (WAT).
Figure 5.
Figure 5.
Exploratory full-brain voxel-based morphometry showing relationships between performance on the Word Associates Test and brain atrophy. Clusters that meet a height threshold of p < 0.005 uncorrected with threshold-free cluster enhancement and a minimum of 25 adjacent voxels are depicted.
See this image and copyright information in PMC

References

    1. Brooks LG, Loewenstein DA (2010) Assessing the progression of mild cognitive impairment to Alzheimer’s disease: current trends and future directions. Alz Res Therapy 2, 28. - PMC - PubMed
    1. Mortamais M, Ash JA, Harrison J, Kaye J, Kramer J, Randolph C, Pose C, Albala B, Ropacki M, Ritchie CW, Ritchie K (2017) Detecting cognitive changes in preclinical Alzheimer’s disease: A review of its feasibility. Alzheimer’s & Dementia 13, 468–492. - PubMed
    1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia 7, 280–292. - PMC - PubMed
    1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia 7, 270–279. - PMC - PubMed
    1. Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Elliott C, Masliah E, Ryan L, Silverberg N (2018) NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia 14, 535–562. - PMC - PubMed

Publication types