Journal of Alzheimer's Disease - Volume 80, issue 4

Authors: Zhang, Baiwen | Lin, Lan | Wu, Shuicai

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a heterogeneous disease with different subtypes. Studying AD subtypes from brain structure, neuropathology, and cognition are of great importance for AD heterogeneity research. Starting from the study of constructing AD subtypes based on the features of T1-weighted structural magnetic resonance imaging, this paper introduces the major connections between the subtype definition and analysis strategies, including brain region-based subtype definition, and their demographic, neuropathological, and neuropsychological characteristics. The advantages and existing problems are analyzed, and reasonable improvement schemes are prospected. Overall, this review offers a more comprehensive view in the field of atrophy subtype in AD, along …with their advantages, challenges, and future prospects, and provide a basis for improving individualized AD diagnosis. Show more

Keywords: Alzheimer’s disease, atrophy subtype, heterogeneity, hippocampal-sparing, limbic-predominant, minimal atrophy Alzheimer’s disease, structural magnetic resonance imaging, typical Alzheimer’s disease

DOI: 10.3233/JAD-201274

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1339-1352, 2021

Authors: Ding, Xu-Long | Tuo, Qing-zhang | Lei, Peng

Article Type: Review Article

Abstract: The detection of plasma tau and its phosphorylation is technically challenging due to the relatively low sensitivity. However, in Alzheimer’s disease and other tauopathies, it is hypothesized that tau in the biofluid may serve as a biomarker. In recent years, several ultrasensitive assays have been developed, which can successfully detect tau and its phosphorylation in various biofluids, and collectively demonstrated the prognostic and diagnostic value of plasma tau/phosphorylated tau. Here we have summarized the principle of four ultrasensitive assays newly developed suitable for plasma tau detection, namely single-molecule array, immunomagnetic reduction assay, enhanced immunoassay using multi-arrayed fiber optics, and meso …scale discovery assay, with their advantages and applications. We have also compared these assays with traditional enzyme-linked-immunosorbent serologic assay, hoping to facilitate future tau-based biomarker discovery for Alzheimer’s disease and other neurodegenerative diseases. Show more

Keywords: Biomarker, enhanced immunoassay using multi-arrayed fiber optics, immunomagnetic reduction assay, meso scale discovery assay, ptau, single-molecule array tau

DOI: 10.3233/JAD-201499

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1353-1362, 2021

Authors: Perez-Valero, Eduardo | Lopez-Gordo, Miguel A. | Morillas, Christian | Pelayo, Francisco | Vaquero-Blasco, Miguel A.

Article Type: Review Article

Abstract: In this paper, we review state-of-the-art approaches that apply signal processing (SP) and machine learning (ML) to automate the detection of Alzheimer’s disease (AD) and its prodromal stages. In the first part of the document, we describe the economic and social implications of the disease, traditional diagnosis techniques, and the fundaments of automated AD detection. Then, we present electroencephalography (EEG) as an appropriate alternative for the early detection of AD, owing to its reduced cost, portability, and non-invasiveness. We also describe the main time and frequency domain EEG features that are employed in AD detection. Subsequently, we examine some of …the main studies of the last decade that aim to provide an automatic detection of AD and its previous stages by means of SP and ML. In these studies, brain data was acquired using multiple medical techniques such as magnetic resonance imaging, positron emission tomography, and EEG. The main aspects of each approach, namely feature extraction, classification model, validation approach, and performance metrics, are compiled and discussed. Lastly, a set of conclusions and recommendations for future research on AD automatic detection are drawn in the final section of the paper. Show more

Keywords: Alzheimer’s disease, early diagnosis, electroencephalography, machine learning

DOI: 10.3233/JAD-201455

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1363-1376, 2021

Authors: Viñuela, Félix | Barro, Angeles

Article Type: Short Communication

Abstract: We evaluated the efficacy and safety of Souvenaid (a multinutrient supplement) in patients with mild Alzheimer’s disease (AD) in real clinical practice and assessed a potential synergistic effect of acetylcholinesterase (AChE) inhibitors. Clinical Dementia Rating (CDR) scale was evaluated after six months follow-up. Patients were divided into 4 groups according to the treatment they received: Souvenaid + AChE inhibitors (n  = 23); only Souvenaid (n  = 8); only AChE inhibitors (n  = 7); no treatment (n  = 16). The Souvenaid + AChE inhibitors and Souvenaid alone groups were associated with significantly lower increases in CDR per month than the AChE inhibitors or no treatment ones. The efficacy of …Souvenaid + AChE inhibitors tended to be higher than Souvenaid alone. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, Fortasyn Connect, observational study, pragmatic clinical trials

DOI: 10.3233/JAD-201357

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1377-1382, 2021

Authors: White, Bartholomew | Lyketsos, Constantine G. | Rosenberg, Paul B. | Oh, Esther S. | Chen, Liam

Article Type: Short Communication

Abstract: As an established treatment for movement disorders, deep brain stimulation (DBS) has been adapted for the treatment of Alzheimer’s disease (AD) by modulating fornix activity. Although it is generally regarded as a safe intervention in patients over 65 years of age, the complex neurophysiology and interconnection within circuits connected to the fornix warrants a careful ongoing evaluation of the true benefit and risk potential of DBS on slowing cognitive decline in AD patients. Here we report on a patient who died long after being implanted with a DBS device who donated her brain for neuropathologic study. The autopsy confirmed multiple …proteinopathies including AD-related change, diffuse neocortical Lewy body disease, TDP-43 proteinopathy, and a nonspecific tauopathy. We discuss the possible mechanisms of these overlapping neurodegenerative disorders and caution that future studies of DBS for AD will need to take these findings into consideration. Show more

Keywords: Alpha-synuclein, Alzheimer’s disease, amyloid-β, deep brain stimulation, Lewy body disease, tau, TDP-43

DOI: 10.3233/JAD-201415

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1383-1387, 2021

Authors: Jardel, Amory | Hopes, Lucie | Malaplate, Catherine | Roch, Véronique | Manca, Chloé | Jonveaux, Thérèse Rivasseau | Verger, Antoine

Article Type: Short Communication

Abstract: This longitudinal study evaluates the prognostic impact of amyloid PET in patients suspected of Alzheimer’s disease and presenting with isolated cerebrospinal fluid (CSF) increases in P-Tau proteins (NCT02556502). The rate of conversion, based on the DSM-5 criteria and all collected data (average follow-up of 39.2±13.2 months), was determined by a panel of experts blinded to the PET results and was 75%(6/8) for positive and 35%(6/17) for negative baseline amyloid PET. In this population with isolated CSF increases in P-Tau, a positive baseline amyloid PET was associated with greater than twice the proportion of dementia conversions within the following three years.

Keywords: Alzheimer’s disease, amyloid PET, cerebrospinal fluid, conversion, longitudinal

DOI: 10.3233/JAD-201435

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1389-1394, 2021

Authors: Kontos, Pia | Radnofsky, Mary L. | Fehr, Phyllis | Belleville, Mike R. | Bottenberg, Frances | Fridley, Mary | Massad, Susan | Grigorovich, Alisa | Carson, Jennifer | Rogenski, Kari | Carpenter, Kyrié S. | Dupuis, Sherry | Battalen, Jill | McDonagh, David | Fassbender, Kathryne | Whitehouse, Peter

Article Type: Article Commentary

Abstract: The rapid emergence of COVID-19 has had far-reaching effects across all sectors of health and social care, but none more so than for residential long-term care homes. Mortality rates of older people with dementia in residential long-term care homes have been exponentially higher than the general public. Morbidity rates are also higher in these homes with the effects of government-imposed COVID-19 public health directives (e.g., strict social distancing), which have led most residential long-term care homes to adopt strict ‘no visitor’ and lockdown policies out of concern for their residents’ physical safety. This tragic toll of the COVID-19 pandemic highlights …profound stigma-related inequities. Societal assumptions that people living with dementia have no purpose or meaning and perpetuate a deep pernicious fear of, and disregard for, persons with dementia. This has enabled discriminatory practices such as segregation and confinement to residential long-term care settings that are sorely understaffed and lack a supportive, relational, and enriching environment. With a sense of moral urgency to address this crisis, we forged alliances across the globe to form Reimagining Dementia: A Creative Coalition for Justice. We are committed to shifting the culture of dementia care from centralized control, safety, isolation, and punitive interventions to a culture of inclusion, creativity, justice, and respect. Drawing on the emancipatory power of the imagination with the arts (e.g., theatre, improvisation, music), and grounded in authentic partnerships with persons living with dementia, we aim to advance this culture shift through education, advocacy, and innovation at every level of society. Show more

Keywords: Arts, coalition, COVID-19, culture change, relational caring, residential long-term care, social justice

DOI: 10.3233/JAD-210057

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1395-1399, 2021

Authors: Dodich, Alessandra | Crespi, Chiara | Santi, Gaia C. | Luzzi, Simona | Ranaldi, Valentina | Iannaccone, Sandro | Marcone, Alessandra | Zamboni, Michele | Cappa, Stefano F. | Cerami, Chiara

Article Type: Research Article

Abstract: Background: Severe socio-emotional impairments characterize the behavioral variant of frontotemporal dementia (bvFTD). However, literature reports social cognition disorders in other dementias. Objective: In this study, we investigated the accuracy of social cognition performances in the early and differential diagnosis of bvFTD. Methods: We included 131 subjects: 32 bvFTD, 26 Alzheimer’s disease (AD), 16 primary progressive aphasia (PPA), 17 corticobasal syndrome (CBS), and 40 healthy control (HC). Each subject completed the Ekman 60 faces (Ek-60F) test assessing basic emotion recognition and the Story-based Empathy Task (SET) assessing attribution of intentions/emotions. A combined social measure (i.e., Emotion Recognition …and Attribution (ERA) index) was calculated. One-way ANOVA has been used to compare performances among groups, while receiver operating characteristic (ROC) curve tested measures ability to distinguish subjects with and without bvFTD. Results: Ek-60F and ERA index scores were significantly lower in bvFTD versus HC, AD, and PPA groups. ROC analyses significantly distinguished bvFTD from HC (AUC 0.82–0.92), with the Ek-60F test showing the highest performance, followed by the ERA index. These two social measures showed the best accuracy in detecting bvFTD from AD (AUC 0.78–0.74) and PPA (AUC 0.80–0.76). Investigated measures failed in detecting bvFTD from CBS. Conclusion: Accuracy analyses support the advantage of using social cognition tests for bvFTD diagnosis. Short social battery may reduce uncertainties and improve disease identification in clinical settings. We recommend a revision of current clinical criteria considering neuropsychological deficits in emotion recognition and processing tasks as key cognitive markers of this neurodegenerative syndrome. Show more

Keywords: Accuracy, behavioral variant of frontotemporal dementia, cognitive marker, diagnosis, emotion recognition, empathy, frontotemporal dementia, social cognition

DOI: 10.3233/JAD-201210

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1401-1411, 2021

Authors: Elverman, Kathleen H. | Paitel, Elizabeth R. | Figueroa, Christina M. | McKindles, Ryan J. | Nielson, Kristy A.

Article Type: Research Article

Abstract: Background: Despite advances in understanding Alzheimer’s disease (AD), prediction of AD prior to symptom onset remains severely limited, even when primary risk factors such as the apolipoprotein E (APOE ) ɛ4 allele are known. Objective: Although executive dysfunction is highly prevalent and is a primary contributor to loss of independence in those with AD, few studies have examined neural differences underlying executive functioning as indicators of risk for AD prior to symptom onset, when intervention might be effective. Methods: This study examined event-related potential (ERP) differences during inhibitory control in 44 cognitively intact older adults (20 …ɛ4+, 24 ɛ4-), relative to 41 young adults. All participants completed go/no-go and stop-signal tasks. Results: Overall, both older adult groups exhibited slower reaction times and longer ERP latencies compared to young adults. Older adults also had generally smaller N200 and P300 amplitudes, except at frontal electrodes and for N200 stop-signal amplitudes, which were larger in older adults. Considered with intact task accuracy, these findings suggest age-related neural compensation. Although ɛ4 did not distinguish elders during go or no-go tasks, this study uniquely showed that the more demanding stop-signal task was sensitive to ɛ4 differences, despite comparable task and neuropsychological performance with non-carriers. Specifically, ɛ4+ elders had slower frontal N200 latency and larger N200 amplitude, which was most robust at frontal sites, compared with ɛ4-. Conclusion: N200 during a stop-signal task is sensitive to AD risk, prior to any evidence of cognitive dysfunction, suggesting that stop-signal ERPs may be an important protocol addition to neuropsychological testing. Show more

Keywords: Alzheimer’s disease, apolipoprotein E ɛ4, compensation, event-related potentials, executive function, inhibition (psychological), neural recruitment

DOI: 10.3233/JAD-201559

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1413-1428, 2021

Authors: Li, Yuanjing | Cong, Lin | Hou, Tingting | Chang, Liguo | Zhang, Chuanchen | Tang, Shi | Han, Xiaolei | Wang, Yongxiang | Wang, Xiang | Kalpouzos, Grégoria | Du, Yifeng | Qiu, Chengxuan

Article Type: Research Article

Abstract: Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI). Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China. Methods: This population-based study included 180 participants (aged≥65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014–2016. We defined aMCI following the Petersen’s criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using …general linear regression models. Results: Multi-adjusted β-coefficient (95% confidence interval) of brain volumes (cm3 ) associated with aMCI was –12.07 (–21.49, –2.64) for global grey matter (GM), –18.31 (–28.45, –8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p  < 0.05). Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes. Show more

Keywords: Amnestic mild cognitive impairment, brain volumes, population-based study, structural magnetic resonance imaging

DOI: 10.3233/JAD-201372

Citation: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1429-1438, 2021