Journal of Alzheimer's Disease - Volume 87, issue 3

Authors: Mirabnahrazam, Ghazal | Ma, Da | Lee, Sieun | Popuri, Karteek | Lee, Hyunwoo | Cao, Jiguo | Wang, Lei | Galvin, James E. | Beg, Mirza Faisal | the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer’s type (DAT). Objective: The goal of this study was to develop and analyze novel biomarkers that can help predict the development and progression of DAT. Methods: We used feature selection and ensemble learning classifier to develop an image/genotype-based DAT score that represents a subject’s likelihood of developing DAT in the future. Three feature types were used: MRI only, genetic only, and combined multimodal data. We used …a novel data stratification method to better represent different stages of DAT. Using a pre-defined 0.5 threshold on DAT scores, we predicted whether a subject would develop DAT in the future. Results: Our results on Alzheimer’s Disease Neuroimaging Initiative (ADNI) database showed that dementia scores using genetic data could better predict future DAT progression for currently normal control subjects (Accuracy = 0.857) compared to MRI (Accuracy = 0.143), while MRI can better characterize subjects with stable mild cognitive impairment (Accuracy = 0.614) compared to genetics (Accuracy = 0.356). Combining MRI and genetic data showed improved classification performance in the remaining stratified groups. Conclusion: MRI and genetic data can contribute to DAT prediction in different ways. MRI data reflects anatomical changes in the brain, while genetic data can detect the risk of DAT progression prior to the symptomatic onset. Combining information from multimodal data appropriately can improve prediction performance. Show more

Keywords: Alzheimer’s disease, biomarker, early detection, machine learning, magnetic resonance imaging, risk scores, single nucleotide polymorphism

DOI: 10.3233/JAD-220021

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1345-1365, 2022

Authors: Fefer, Gilad | Panek, Wojciech K. | Khan, Michael Z. | Singer, Matthew | Westermeyer, Hans D. | Mowat, Freya M. | Murdoch, David M. | Case, Beth | Olby, Natasha J. | Gruen, Margaret E.

Article Type: Research Article

Abstract: Background: Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners. Objective: This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration. Methods: Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive …Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL. Results: CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r  = –0.47, p  = 0.002), inhibitory control (r  = –0.51, p  = 0.002), detour (r  = –0.43, p  = 0.001), and pNfL (r  = 0.41, p  = 0.025). Concentration of pNfL correlated with inhibitory control (r  = –0.7, p ≤0.001). The CCDR scale correlated with performance on inhibitory control (r  = –0.46, p  = 0.005). Conclusion: Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs. Show more

Keywords: Blood biomarkers, canine cognitive dysfunction syndrome, CCDS, cognitive testing, dementia, neurofilament light chain, NfL

DOI: 10.3233/JAD-215562

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1367-1378, 2022

Authors: Llamas-Rodríguez, Josué | Oltmer, Jan | Greve, Douglas N. | Williams, Emily | Slepneva, Natalya | Wang, Ruopeng | Champion, Samantha | Lang-Orsini, Melanie | Fischl, Bruce | Frosch, Matthew P. | van der Kouwe, André J.W. | Augustinack, Jean C.

Article Type: Research Article

Abstract: Background: Neurofibrillary tangle (NFT) accumulation in the entorhinal cortex (EC) precedes the transformation from cognitive controls to mild cognitive impairment and Alzheimer’s disease (AD). While tauopathy has been described in the EC before, the order and degree to which the individual subfields within the EC are engulfed by NFTs in aging and the preclinical AD stage is unknown. Objective: We aimed to investigate substructures within the EC to map the populations of cortical neurons most vulnerable to tau pathology in aging and the preclinical AD stage. Methods: We characterized phosphorylated tau (CP13) in 10 cases at …eight well-defined anterior-posterior levels and assessed NFT density within the eight entorhinal subfields (described by Insausti and colleagues) at the preclinical stages of AD. We validated with immunohistochemistry and labeled the NFT density ratings on ex vivo MRIs. We measured subfield cortical thickness and reconstructed the labels as three-dimensional isosurfaces, resulting in anatomically comprehensive, histopathologically validated tau “heat maps.” Results: We found the lateral EC subfields ELc, ECL, and ECs (lateral portion) to have the highest tau density in semi-quantitative scores and quantitative measurements. We observed significant stepwise higher tau from anterior to posterior levels (p  < 0.001). We report an age-dependent anatomically-specific vulnerability, with all cases showing posterior tau pathology, yet older individuals displaying an additional anterior tau burden. Finally, cortical thickness of each subfield negatively correlated with respective tau scores (p  < 0.05). Conclusion: Our findings indicate that posterior-lateral subfields within the EC are the most vulnerable to early NFTs and atrophy in aging and preclinical AD. Show more

Keywords: Aging, cross-sectional, entorhinal cortex, histological labeling, immunohistochemistry, neuropathology, tauopathy, temporal lobe, three-dimensional imaging, validation study

DOI: 10.3233/JAD-215567

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1379-1399, 2022

Authors: Lei, Lauren K.S. | Lam, Bess Y.H. | Lai, Daniel W.L. | Bai, Xue | Li, Jessica | Zou, Zhi | Chan, Chetwyn C.H.

Article Type: Research Article

Abstract: Background: The Montreal Cognitive Assessment (MoCA) is a standard test for screening and monitoring cognitive functions. Objective: This study explored the two-year changes in MoCA scores in older adults. Methods: Fifty-seven participants with mild cognitive impairment (MCI) and 87 participants with normal cognition completed the baseline and two-year follow-up assessments. Apart from MoCA, tests on visuospatial judgment, memory, and motor-related executive function were administered. Results: The results identified three MCI subgroups based on the differential changes in MoCA scores. They were the consistently low, consistently high, and low-to-high between-time performances. These heterogeneous test performances …are on contrary to the significant deteriorations in executive function and finger dexterity across all subgroups. Repeated exposure to MoCA tests during the follow-up period was found to be a plausible indicator of the MCI subgroup categorization. Conclusion: Findings raise concerns over adopting brief clinical instrument for repeated testing, such as MoCA, for monitoring MCI conditions among older adults. Show more

Keywords: Aging, mild cognitive impairment, montreal cognitive assessment

DOI: 10.3233/JAD-220003

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1401-1412, 2022

Authors: Daly, Timothy | Mastroleo, Ignacio

Article Type: Book Review

DOI: 10.3233/JAD-220185

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1413-1414, 2022

Article Type: Correction

DOI: 10.3233/JAD-229004

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1415-1415, 2022

Article Type: Correction

DOI: 10.3233/JAD-229005

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1417-1417, 2022