Journal of Alzheimer's Disease - Volume 98, issue 1

Authors: Shea, Tom | Szaro, Ben

Article Type: Obituary

DOI: 10.3233/JAD-249005

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 1-2, 2024

Authors: Ross, John Paul | Post, Stephen G. | Scheinfeld, Laurel

Article Type: Review Article

Abstract: Background: Even in severe states of Alzheimer’s disease and related dementias (ADRD), accounts of an unexpected or paradoxical return of awareness and lucidity have been reported in some patients, documented formally, and studied. Objective: A scoping review was undertaken to survey the literature on the topic. Methods: Five databases were searched using pertinent search terms. Results were deduplicated and subsequently screened by title and abstract for relevance. Remaining reports were read and included or excluded using specific inclusion criteria. 30 results consisted of a mix of perspective papers, case reports, qualitative surveys of caregivers, law journal …comments, and mechanistic speculation. Results: An equal mix of primary and secondary research was identified. Conclusions: The papers collected in this review provide a valuable methodological outline for researching the topic of lucid episodes in ADRD. The verified legitimacy and simultaneous inexplicability of these events promote philosophical discussion, mechanistic investigations, and sorely needed research in the field of ADRD. Show more

Keywords: Alzheimer’s disease, awareness, caregivers, dementia, lucidity, neurodegenerative disorders, paradoxical lucidity, terminal lucidity, unexpected lucidity

DOI: 10.3233/JAD-231396

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 3-11, 2024

Authors: Li, Zhirui | Fan, Zixuan | Zhang, Qian

Article Type: Systematic Review

Abstract: Background: Cerebrospinal fluid (CSF) or blood biomarkers like phosphorylated tau proteins (p-tau) are used to detect Alzheimer’s disease (AD) early. Increasing studies on cognitive function and blood or CSF p-tau levels are controversial. Objective: Our study examined the potential of p-tau as a biomarker of cognitive status in normal control (NC), mild cognitive impairment (MCI), and AD patients. Methods: We searched PubMed, Cochrane, Embase, and Web of Science for relevant material through 12 January 2023. 5,017 participants from 20 studies—1,033 AD, 2,077 MCI, and 1,907 NC—were evaluated. Quantitative analysis provided continuous outcomes as SMDs with 95% …CIs. Begg tested publication bias. Results: MCI patients had lower CSF p-tau181 levels than AD patients (SMD =−0.60, 95% CI (−0.85, −0.36)) but higher than healthy controls (SMD = 0.67). AD/MCI patients had greater plasma p-tau181 levels than healthy people (SMD =−0.73, 95% CI (−1.04, −0.43)). MCI patients had significantly lower p-tau231 levels than AD patients in plasma and CSF (SMD =−0.90, 95% CI (−0.82, −0.45)). MCI patients showed greater CSF and plasma p-tau231 than healthy controls (SMD = 1.34, 95% CI (0.89, 1.79) and 0.43, (0.23, 0.64)). Plasma p-tau181/231 levels also distinguished the three categories. MCI patients had higher levels than healthy people, while AD patients had higher levels than MCI patients. Conclusions: CSF p-tau181 and p-tau231 biomarkers distinguished AD, MCI, and healthy populations. Plasma-based p-tau181 and p-tau231 biomarkers for AD and MCI need further study. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, mild cognitive impairment, phosphorylated tau 181, phosphorylated tau 231, plasma

DOI: 10.3233/JAD-230799

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 13-32, 2024

Authors: Rossi, Eleonora | Marrosu, Francesco | Saba, Luca

Article Type: Systematic Review

Abstract: Background: Alzheimer’s disease (AD) is a complex condition that affects various aspects of a patient’s life. Music therapy may be considered a beneficial supplementary tool to traditional therapies, that not fully address the range of AD manifestations. Objective: The purpose of this systematic review is to investigate whether music therapy can have a positive impact on AD patients and on which symptoms. Methods: The main research databases employed have been PubMed and Cochrane, using the keywords “dementia”, “music therapy”, “Alzheimer”, “fMRI”, “music”, and “EEG”. Results: After removing duplicates and irrelevant studies, 23 were screened …using set criteria, resulting in the final inclusion of 15 studies. The total number of participants included in these studies has been of 1,196 patients. For the fMRI analysis the search resulted in 28 studies on PubMed, two of which were included in the research; the total number of participants was of 124 individuals. The studies conducted with EEG were found using PubMed. The initial search resulted in 15 studies, but after a more accurate evaluation only 2 have been included in the analysis. Conclusions: Even though the data currently available is not sufficient to draw conclusions supported by robust statistical power, the impact of music therapy on AD neuropsychiatric symptoms deserves great interest. Further research should be ushered, possibly multicentric studies, led with neuroimaging and other recent techniques, which can eventually open views on the music role in improving the cognitive status in AD. Show more

Keywords: Alzheimer’s disease, cognitive function, dementia, EEG, fMRI, mild cognitive impairment, music therapy, neuropsychiatric symptoms, systematic review

DOI: 10.3233/JAD-230852

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 33-51, 2024

Authors: Cotta Ramusino, Matteo | Scanu, Lucia | Gritti, Linda | Imbimbo, Camillo | Farina, Lisa Maria | Cosentino, Giuseppe | Perini, Giulia | Costa, Alfredo

Article Type: Systematic Review

Abstract: Background: The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer’s disease, have been recently defined, while little is known about its neurophysiological correlates. Objective: To describe neurophysiological alterations of the visual pathway as assessed using visual field test (VF), visual evoked potentials (VEP), and electroretinogram (ERG) in PCA patients. Methods: Studies reporting VF, VEPs, and ERG in PCA patients were selected according PRISMA method. Of the 323 articles that emerged from the literature, 17 included the outcomes of interest. To these data, we added those derived from a patient cohort …enrolled at our clinic. Results: The literature review included 140 patients, half of them (50%) presented with homonymous hemianopia or quadrantanopia. VEPs were available in 4 patients (2 normal findings, 1 decreased amplitude, and 1 increased latency) and ERG in 3 patients (substantially normal findings). Our case series included 6 patients, presenting with homonymous lateral hemianopia in 50% and contralateral cortical atrophy. VEPs showed normal amplitude in 66–83% according to the stimulation check, and increased latency in 67% in absence of myelin damage on MRI. Latency was increased in both eyes in 50% and only on one side in the other 50%. Such alterations were observed in patients with more severe and symmetric atrophy. ERG showed normal findings. Conclusions: Neurophysiological investigations of the visual pathway in PCA are almost absent in literature. Alterations involve both amplitude and latency and can be also monocular. A multiple-point involvement of the optical pathway can be hypothesized. Show more

Keywords: Alzheimer’s disease, electroretinogram, posterior cortical atrophy, visual evoked potentials, visual field

DOI: 10.3233/JAD-231123

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 53-67, 2024

Authors: Gills, Joshua L. | Bubu, Omonigho M.

Article Type: Article Commentary

Abstract: Impairments of the sleep architecture due to disrupted sleep in individuals with obstructive sleep apnea (OSA) may result in reduced slow wave sleep (SWS), intermittent hypoxemia, and excessive day time sleepiness— all factors that have been shown to impact Alzheimer’s disease (AD) risk. In this commentary, we comment on the work by Cavuoto and colleagues in which they examine the associations between nocturnal hypoxemia or sleep disruptions (during SWS) and amyloid-β burden in individuals with OSA. We review the findings in the context of other similar studies and highlight the strengths and weaknesses of these published studies. We note the …importance of examining these relationships longitudinally with a large sample size, including considering sleep health disparities, vascular components, and multiple cognitive domain tests. Show more

Keywords: Alzheimer’s disease, amyloid burden, cognition, obstructive sleep apnea, slow wave sleep

DOI: 10.3233/JAD-231385

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 69-73, 2024

Authors: Siafarikas, Nikias

Article Type: Article Commentary

Abstract: Neuropsychiatric symptoms (NPS) are increasingly being recognized as clinical markers for incipient dementia in Alzheimer’s disease (AD dementia). NPS may reinforce cognitive impairment or decline and vice versa. Although NPS are frequent already in mild cognitive impairment, their mechanisms are poorly understood. It is unclear if they share biological mechanisms with cognitive symptoms and how they are associated to structural brain changes, but evidence suggests associations of NPS to cerebral atrophy. An additional NPS dimension in AD dementia concepts might add valuable information to detect patients at risk for AD dementia.

Keywords: Alzheimer’s disease, cerebral atrophy, dementia, mild cognitive impairment, neuroimaging, neuropsychiatric symptoms

DOI: 10.3233/JAD-231418

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 75-78, 2024

Authors: Talan, Jamie

Article Type: Editorial

Keywords: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, ALSP, ALSP Foundation, cerebral white matter degeneration, CSF1R mutation, Zbigniew K. Wszolek

DOI: 10.3233/JAD-249003

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 79-82, 2024

Authors: Prabhakaran, Divya | Grant, Caroline | Pedraza, Otto | Caselli, Richard | Athreya, Arjun P. | Chandler, Melanie

Article Type: Research Article

Abstract: Background: Identifying individuals at risk for mild cognitive impairment (MCI) is of urgent clinical need. Objective: This study aimed to determine whether machine learning approaches could harness longitudinal neuropsychology measures, medical data, and APOE ɛ 4 genotype to identify individuals at risk of MCI 1 to 2 years prior to diagnosis. Methods: Data from 676 individuals who participated in the ‘APOE in the Predisposition to, Protection from and Prevention of Alzheimer’s Disease’ longitudinal study (N  = 66 who converted to MCI) were utilized in supervised machine learning algorithms to predict conversion to MCI. …Results: A random forest algorithm predicted conversion 1–2 years prior to diagnosis with 97% accuracy (p  = 0.0026). The global minima (each individual’s lowest score) of memory measures from the ‘Rey Auditory Verbal Learning Test’ and the ‘Selective Reminding Test’ were the strongest predictors. Conclusions: This study demonstrates the feasibility of using machine learning to identify individuals likely to convert from normal cognition to MCI. Show more

Keywords: Aging, Alzheimer’s disease, APOE , machine learning, mild cognitive impairment, neuropsychology

DOI: 10.3233/JAD-230556

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 83-94, 2024

Authors: Yang, Jingjing | Liu, Xizhu | Oveisgharan, Shahram | Zammit, Andrea R. | Nag, Sukriti | Bennett, David A. | Buchman, Aron S.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease neuropathologic changes (AD-NC) are important to identify people with high risk for AD dementia (ADD) and subtyping ADD. Objective: Develop imputation models based on clinical measures to infer AD-NC. Methods: We used penalized generalized linear regression to train imputation models for four AD-NC traits (amyloid-β, tangles, global AD pathology, and pathologic AD) in Rush Memory and Aging Project decedents, using clinical measures at the last visit prior to death as predictors. We validated these models by inferring AD-NC traits with clinical measures at the last visit prior to death for independent Religious Orders …Study (ROS) decedents. We inferred baseline AD-NC traits for all ROS participants at study entry, and then tested if inferred AD-NC traits at study entry predicted incident ADD and postmortem pathologic AD. Results: Inferred AD-NC traits at the last visit prior to death were related to postmortem measures with R2  = (0.188,0.316,0.262) respectively for amyloid-β, tangles, and global AD pathology, and prediction Area Under the receiver operating characteristic Curve (AUC) 0.765 for pathologic AD. Inferred baseline levels of all four AD-NC traits predicted ADD. The strongest prediction was obtained by the inferred baseline probabilities of pathologic AD with AUC = (0.919,0.896) for predicting the development of ADD in 3 and 5 years from baseline. The inferred baseline levels of all four AD-NC traits significantly discriminated pathologic AD profiled eight years later with p -values < 1.4×10-10 . Conclusions: Inferred AD-NC traits based on clinical measures may provide effective AD biomarkers that can estimate the burden of AD-NC traits in aging adults. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease neurologic change, computational modeling, dementia, pathology

DOI: 10.3233/JAD-230639

Citation: Journal of Alzheimer's Disease, vol. 98, no. 1, pp. 95-107, 2024