Journal of Alzheimer's Disease - Volume 82, issue 1

Authors: Rodrigo-Herrero, Silvia | Luque-Tirado, Andrea | Méndez-Barrio, Carlota | García-Solís, David | Bernal Sánchez-Arjona, María | Oropesa-Ruiz, Juan Manuel | Maillet, Didier | Franco-Macías, Emilio

Article Type: Research Article

Abstract: Background: The Memory Associative Test TMA-93 examines visual relational binding, characteristically affected in early-AD stages. Objective: We aim to validate the TMA-93 by biomarkers determination and compare its diagnostic characteristics with the Free and Cued Selective Reminding Test (FCSRT). Methods: Retrospective analysis of a Biobank database. Patients’ records initially consulted for memory complaints, scored MMSE≥22, had TMA-93 and FCSRT tested, and AD biomarker determination (Amyloid-PET or CSF), either positive or negative, were selected. As cutoffs, we considered the 10-percentile for TMA-93 (P10/TMA-93), and “total free recall” (TFR) 21/22, total recall (TR) 43/44, and Cued Index < 0.77 …for FCSRT from previous Spanish validation and normative studies. Diagnostic utilities were calculated using ROC curves and compared by the DeLong method. We studied if one test improved the other test’s prediction, following a forward stepwise logistic regression model. Results: We selected 105 records: 64 “positive” and 41 “negative” biomarkers. TMA-93 total score diagnostic utility (AUC = 0.72; 95%CI:0.62–0.82) was higher than those of the FCSRT: TFR (AUC = 0.70; 95%CI: 0.60–0.80), TR (AUC = 0.63; 95%CI:0.53–0.74), and Cued Index (AUC = 0.62; 95%CI:0.52–0.73). The P10/TMA-93 cutoff showed 86%sensitivity, similar to that of the most sensitive FCSRT cutoff (TFR21/22, 89%) and 29%specificity, lower than that of the most specific FCSRT cutoff (Cued Index < 0.77, 57%). 32.8%of the positive-biomarker group scored above CI/0.77 but below p10TMA-93. The addition of TMA-93 total score to FCSRT variables improved significantly the biomarkers results’ prediction. Conclusion: TMA-93 demonstrated “reasonable” diagnostic utility, similar to FCSRT, for discriminating AD biomarker groups. TMA-93 total score improved the AD biomarker result prediction when added to FCSRT variables. Show more

Keywords: Alzheimer’s disease, amyloid-PET, biomarker, cerebrospinal fluid, free and cued selective reminding test, TMA-93

DOI: 10.3233/JAD-210115

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 401-410, 2021

Authors: Soo, See Ann | Ng, Kok Pin | Wong, Fennie | Saffari, Seyed Ehsan | Yatawara, Chathuri | Ismail, Zahinoor | Kandiah, Nagaendran

Article Type: Research Article

Abstract: Background: Mild behavioral impairment (MBI) describes persistent behavioral changes in later life as an at-risk state for dementia. While cardiovascular risk factors (CVRFs) are linked to dementia, it is uncertain how CVRFs are associated with MBI. Objective: To determine the prevalence of MBI and its association with CVRFs among cognitively normal (CN) and mild cognitive impairment (MCI) individuals in Singapore. Methods: 172 individuals (79 CN and 93 MCI) completed the MBI-checklist (MBI-C). The prevalence of MBI and MBI-C sub-domain characteristics among CN and MCI were examined. Regression models evaluated the relationships between MBI-C sub-domain scores with …CVRFs. Results: The prevalence of MBI and mean MBI-C total score were significantly higher among MCI than CN (34.4%versus 20.3%, p  = 0.022 and 7.01 versus 4.12, p  = 0.04). The highest and lowest-rated sub-domains among CN and MCI were impulse dyscontrol and abnormal thoughts and perception respectively. Within the MCI cohort, a higher proportion of individuals with diabetes mellitus (DM) had MBI compared to individuals without DM (28.1%versus 10.4%, p  = 0.025). The interaction of DM and MCI cohort resulted in significantly higher mean MBI-C total, decreased motivation, emotional dysregulation, impulse dyscontrol, and abnormal thoughts and perception sub-domain scores. Conclusion: The prevalence of MBI is higher among a Singapore cohort compared to Caucasian cohorts. The associations of DM with both the presence and severity of MBI among MCI suggest that DM may be a risk factor for MBI. The optimization of DM may be a potential therapeutic approach to improve clinical outcomes among MCI with MBI. Show more

Keywords: Behavior, cardiovascular diseases, cognitive dysfunction, dementia, diabetes mellitus

DOI: 10.3233/JAD-210037

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 411-420, 2021

Authors: Jiménez, Elizabeth Carolina | Sierra-Marcos, Alba | Romeo, August | Hashemi, Amin | Leonovych, Oleksii | Bustos Valenzuela, Patricia | Solé Puig, Maria | Supèr, Hans

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is characterized by progressive deterioration of cognitive functions and may be preceded by mild cognitive impairment (MCI). Evidence shows changes in pupil and vergence responses related to cognitive processing of visual information. Objective: Here we test the hypothesis that MCI and AD are associated with specific patterns in vergence and pupil responses. Methods: We employed a visual oddball task. In the distractor condition (80%of the trials), a blue stimulus was presented whereas in the target condition (20%of trials) it was red. Participants (23 Controls, 33 MCI patients, and 18 AD patients) were …instructed to press a button when a target appeared. Results: Participants briefly converged their eyes 200 ms after stimulus presentation. In controls, this transient peak response was followed by a delay response to targets but not to distractor stimuli. In the patient groups, delay responses to distractors were noticed. Consequently, the differential vergence response was strong in the control group, weak in the MCI group, and absent in the AD group. Pupils started to dilate 500–600 ms after the appearance of a target but slightly contracted after the presentation of a distractor. This differential pupil response was strongest in the AD group. Conclusion: Our findings support the idea of a role of vergence and pupil responses in attention and reveal altered responses in MCI and AD patients. Further studies should assess the value of vergence and pupil measurements as an objective support tool for early diagnosis of AD. Show more

Keywords: Attention, binocular eye movement, convergence, dementia, Edinger-Westphal, fixational eye movement, locus coeruleus, mild cognitive impairment, neurodegeneration, oculomotor behavior

DOI: 10.3233/JAD-201301

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 421-433, 2021

Authors: Sharma, Namita | Murari, Geetanjali | Vandermorris, Susan | Verhoeff, Nicolaas Paul L.G. | Herrmann, Nathan | Chen, J. Jean | Mah, Linda

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer’s disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. Objective: To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magnetic resonance imaging. Methods: Forty-nine participants with either SCD (n  = 23, 12 females; mean age: 70.7 (5.5)) or who were cognitively unimpaired (CU; n  = 26, 16 females, mean age: 71.42 (7.3)) completed the …Memory Functioning Questionnaire, a measure of subjective memory, and underwent resting state functional MRI at 3 Tesla. Functional connectivity between the posterior cingulate cortex (PCC), as the key pDMN node, and MTL regions were compared between SCD and CU groups. Further, the association between pDMN-MTL connectivity and the Frequency of Forgetting subscale of the Memory Functioning Questionnaire was examined. Results: Connectivity between the PCC-MTL was observed in the CU group but was absent in SCD (t (47) = 2.69, p  = 0.01). Across all participants, self-perception of frequency of forgetting, but not objective memory, was strongly correlated with connectivity between the PCC-left parahippocampal gyrus (r  = 0.43, p  = 0.002). Conclusion: These findings support the hypothesis that increased AD risk in SCD may be mediated by disrupted pDMN-parahippocampal connectivity. In addition, these findings suggest that frequency of forgetting may serve as a potential biomarker of SCD due to incipient AD. Show more

Keywords: Alzheimer’s disease, default mode network, depression, functional connectivity, memory functioning questionnaire, parahippocampal gyrus, posterior cingulate cortex, resting state functional magnetic resonance imaging, subjective cognitive decline, subjective memory

DOI: 10.3233/JAD-201579

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 435-445, 2021

Authors: Pistono, Aurélie | Senoussi, Mehdi | Guerrier, Laura | Rafiq, Marie | Giméno, Mélanie | Péran, Patrice | Jucla, Mélanie | Pariente, Jérémie

Article Type: Research Article

Abstract: Background: Language production deficits occur early in the course of Alzheimer’s disease (AD); however, only a few studies have focused on language network’s functional connectivity in mild cognitive impairment (MCI) due to AD. Objective: The current study aims to uncover the extent of language alteration at the MCI stage, at a behavioral and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI. Methods: Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the …left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks. Results: MCI due to AD participants had language impairment during standardized language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multivariate pattern analyses could significantly predict participants’ group. Language network’s functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage, positively correlated with language performance. Conclusion: Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language. Show more

Keywords: Alzheimer’s disease, connected speech, functional connectivity, functional MRI, language, multivariate pattern analysis

DOI: 10.3233/JAD-201584

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 447-460, 2021