Journal of Alzheimer's Disease - Volume 101, issue 4

Authors: Saido, Takaomi C.

Article Type: Obituary

DOI: 10.3233/JAD-240903

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1027-1028, 2024

Authors: Spencer, Felicity S.E. | Elsworthy, Richard J. | Breen, Leigh | Bishop, Jonathan | Morrissey, Sol | Aldred, Sarah

Article Type: Review Article

Abstract: Background: Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer’s disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. Objective: The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. Methods: UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing …speed, and reaction time). Logistic and linear regression models were conducted. Results: 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR = 0.63, 95% CI [0.40, 1.00], p  = 0.047) and accelerometer-assessed (OR = 0.96 [0.93, 0.98], p  = 0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (β= – 65.43 [– 109.68, – 17.40], p  = 0.007), and larger total brain volume (β= 4398.46 [165.11, 8631.82], p  < 0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (β= – 0.43 [– 0.68, – 0.18], p  = 0.001); though poorer visuospatial ability (β= – 0.06 [– 0.09, – 0.03], p  < 0.001), and executive function (β= 0.49 [0.31, 0.66], p  < 0.001; β= 0.27 [0.10, 0.45], p  = 0.002) was related to self-reported physical activity levels. Conclusions: Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis. Show more

Keywords: Alzheimer’s disease, apolipoprotein E4, brain, cognition, exercise, sex, UK Biobank

DOI: 10.3233/JAD-240269

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1029-1042, 2024

Authors: Bolshakov, Alexey P. | Gerasimov, Konstantin | Dobryakova, Yulia V.

Article Type: Review Article

Abstract: This review is an attempt to compile existing hypotheses on the mechanisms underlying the initiation and progression of Alzheimer’s disease (AD), starting from sensory impairments observed in AD and concluding with molecular events that are typically associated with the disease. These events include spreading of amyloid plaques and tangles of hyperphosphorylated tau and formation of Hirano and Biondi bodies as well as the development of oxidative stress. We have detailed the degenerative changes that occur in several neuronal populations, including the cholinergic neurons in the nucleus basalis of Meynert, the histaminergic neurons in the tuberomammillary nucleus, the serotonergic neurons in …the raphe nuclei, and the noradrenergic neurons in the locus coeruleus. Furthermore, we discuss the potential role of iron accumulation in the brains of subjects with AD in the disease progression which served as a basis for the idea that iron chelation in the brain may mitigate oxidative stress and decelerate disease development. We also draw attention to possible role of sympathetic system and, more specifically, noradrenergic neurons of the superior cervical ganglion in triggering of the disease. We also explore the alternative possibility of compensatory protective changes that may occur in these neurons to support cholinergic function in the forebrain of subjects with AD. Show more

Keywords: Alzheimer’s disease, amyloid, astrocytes, cholinergic neurons, noradrenergic neurons, neurodegeneration, oxidative stress, sympathetic system, tauopathy

DOI: 10.3233/JAD-240620

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1043-1061, 2024

Authors: Schicktanz, Silke | Alpinar-Segawa, Zümrüt | Ulitsa, Natalie | Perry, Julia | Werner, Perla

Article Type: Review Article

Abstract: Biomarkers for predicting Alzheimer’s disease (AD) are advancing and their implementation in various healthcare systems is imminent. There is a need for ethical standards addressing information needs, socio-ethical concerns, and expectations of healthy and at-risk persons. We present an ethical approach that integrates different existing ethical frameworks and discussion of our empirical, cross-cultural findings in a multi-layered perspective by addressing three levels. The micro-level focuses on the communication between counseling professionals, persons at risk or in an early stage of dementia, and family members. The meso-level addresses interprofessional cooperation and exchange as a key element for best person-centered care. The …macro-level considers public health promotion, the media, and public-funded research. This approach allows to address key ethical concepts including beneficence, non-maleficence, autonomy, informational self-determination, empowerment, and justice. Our contribution specifically examines the ethical challenges associated with AD prediction by means of biomarkers, based on insights from a German-Israeli comparison, and promotes a transdisciplinary discussion across different healthcare contexts. We propose a reflection on three levels to go beyond the clinical counseling context and to consider the rapidly evolving field of biomarkers in the coming years. Our ethical-practical recommendations should not be considered final, but rather procedural and will require continuous adaptation regarding culturally varying practices, new algorithms, meta-analyses, and re-evaluation of established recommendations. Show more

Keywords: Alzheimer’s disease, communication, counseling, cross-cultural comparison, dementia, ethical recommendations, literacy, prediction

DOI: 10.3233/JAD-231137

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1063-1081, 2024

Authors: Hamedani, Mehrnaz | Caneva, Stefano | Mancardi, Gian Luigi | Alì, Paolo Alessandro | Fiaschi, Pietro | Massa, Federico | Schenone, Angelo | Pardini, Matteo

Article Type: Systematic Review

Abstract: Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder which primarily involves memory and cognitive functions. It is increasingly recognized that motor involvement is also a common and significant aspect of AD, contributing to functional decline and profoundly impacting quality of life. Motor impairment, either at early or later stages of cognitive disorders, can be considered as a proxy measure of cognitive impairment, and technological devices can provide objective measures for both diagnosis and prognosis purposes. However, compared to other neurodegenerative disorders, the use of technological tools in neurocognitive disorders, including AD, is still in its infancy. …Objective: This report aims to evaluate the role of technological devices in assessing motor involvement across the AD spectrum and in other dementing conditions, providing an overview of the existing devices that show promise in this area and exploring their clinical applications. Methods: The evaluation involves a review of the existing literature in the PubMed, Web of Science, Scopus, and Cochrane databases on the effectiveness of these technologies. 21 studies were identified and categorized as: wearable inertial sensors/IMU, console/kinect, gait analysis, tapping device, tablet/mobile, and computer. Results: We found several parameters, such as speed and stride length, that appear promising for detecting abnormal motor function in MCI or dementia. In addition, some studies have found correlations between these motor aspects and cognitive state. Conclusions: Clinical application of technological tools to assess motor function in people with cognitive impairments of a neurodegenerative nature, such as AD, may improve early detection and stratification of patients. Show more

Keywords: Alzheimer’s disease, cognitive impairment, dementia, mild cognitive impairment, motor function, sensors, technology assessment

DOI: 10.3233/JAD-240559

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1083-1106, 2024

Authors: Sharma, Rishabh | Gill, Jasdeep Kaur | Chhabra, Manik | Carter, Caitlin | Alkabbani, Wajd | Vidyasagar, Kota | Chang, Feng | Lee, Linda | Patel, Tejal

Article Type: Systematic Review

Abstract: Background: Older adults with dementia who are on polypharmacy are more vulnerable to the use of potentially inappropriate medications (PIM), which can significantly increase the risk of adverse events and drug-related problems (DRPs). Objective: This systematic review and meta-analysis were conducted to map the prevalence of PIM use, polypharmacy, and hyper-polypharmacy among older adults with cognitive impairment or dementia attending memory clinics. Methods: Ovid MEDLINE, Ovid EMBASE, Scopus, Cochrane Library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) were systematically searched from inception to April 22, 2024. Observational studies assessing the PIMs use among older adults …with CI or dementia were screened. A random- effects meta-analysis was conducted to pool the prevalence estimates. Results: Of 5,787 identified citations, 11 studies including 4,571 participants from 8 countries were included. Among all the included studies the pooled prevalence of PIM use was 38% (95% confidence interval (CIn): 27– 50%), highlighting a notable range from 20% to 78%. The analysis identified anticholinergics, benzodiazepines, and non-benzodiazepine sedatives as the most common PIMs. Subgroup analysis revealed a higher pooled prevalence of PIM in the USA (39%; 95% CIn: 10– 78, I2 (%) = 98, 3 studies) and Australia (36%, 95% CIn: 12– 70, I2 (%) = 96, 2 Studies). Additionally, pooled prevalence of polypharmacy and hyper-polypharmacy was reported as (60%; 95% CIn: 46– 73, I2 (%) = 95, 3 studies), and (The prevalence of hyper-polypharmacy was 17.6%; 1 study) respectively. Conclusions: The definition of PIMs significantly impacts study results, often more than geographical variations. The variability in criteria and tools like the Beers or Screening Tool of Older Persons’ Prescriptions (STOPP) criteria across studies and regions leads to differing prevalence rates. Show more

Keywords: Alzheimer’s disease, cognitive impairment, dementia, older adults, potentially inappropriate medication

DOI: 10.3233/JAD-240575

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1107-1120, 2024

Authors: Ryoo, Nayoung | Suh, Jeewon | Son, Eun Ji | Park, Young Ho | Kim, SangYun

Article Type: Short Communication

Abstract: Background: Subjective cognitive decline (SCD) refers to self-reported cognitive decline in individuals with normal performance on standardized cognitive tests. Understanding the factors predicting progression from SCD to mild cognitive impairment (MCI) is crucial, as approximately 14% of SCD cases progress to dementia and about 27% develop MCI over four years. Objective: This study aims to identify neuropsychological predictors of progression from SCD to MCI, focusing on cognitive domains assessed through neuropsychological tests. Methods: This retrospective study at Seoul National University Bundang Hospital analyzed a cohort of 107 patients diagnosed with SCD through comprehensive assessment. Patients underwent …annual neuropsychological testing, including the Digit Span Test, Boston Naming Test, Rey Complex Figure Test, Seoul Verbal Learning Test, and Stroop Test. Results: Annually, these patients underwent neuropsychological tests over a 5-year period; 24 progressed to MCI per NIA-AA criteria. Key predictors of MCI progression included age, ischemic heart disease, and scores from the forward digit span, delayed recall, and Boston naming tests. Lower scores in delayed recall and Boston naming tests significantly correlated with a higher risk of MCI (p  < 0.001). Conclusions: These findings suggest a need for targeted management of memory and language functions to monitor disease progression effectively. Show more

Keywords: Alzheimer’s disease, mild cognitive impairment, neuropsychological tests, preclinical Alzheimer’s disease, progressive subjective cognitive decline, subjective cognitive decline

DOI: 10.3233/JAD-231042

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1121-1126, 2024

Authors: Sato, Kenichiro | Niimi, Yoshiki | Ihara, Ryoko | Iwata, Atsushi | Iwatsubo, Takeshi

Article Type: Short Communication

Abstract: Anti-amyloid drugs for early Alzheimer’s disease, including lecanemab, are associated with adverse events (AEs), such as amyloid-related imaging abnormalities (ARIA)-edema/effusion (E), ARIA-hemorrhage, and infusion-related reactions, which can indicate allocated arms in clinical trials. Herein, we evaluated the predictive value of AEs using a meta-analysis to estimate their incidence and simulated positive predictive value (PPV). The PPV for ARIA-E was high (0.915), but that for ARIA hemorrhage was low (0.630). Infusion-related reactions had a high PPV of 0.910, but with a wide confidence interval. Our results suggest the need to ameliorate the unblinding effects of AEs, particularly ARIA-E in trials.

Keywords: Adverse event, Alzheimer’s disease, anti-amyloid drug, clinical trial, unblinding

DOI: 10.3233/JAD-240623

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1127-1132, 2024

Authors: Vyhnalek, Martin | Laczó, Martina | Laczó, Jan

Article Type: Article Commentary

Abstract: Hippocampal dysfunction is associated with early clinical signs of Alzheimer’s disease (AD). Due to the limited availability or invasiveness of current biomarkers, the AD diagnosis is usually based on cognitive assessment and structural brain imaging. The recent study by Lalive and colleagues examined the specificity of brain morphometry for the AD diagnosis in a memory clinic cohort with hippocampal-type amnestic syndrome. The results indicate that memory deficits and hippocampal atrophy are similar in AD and non-AD patients, highlighting their low diagnostic specificity. These findings challenge the traditional AD diagnosis and underscore the need for biomarkers to differentiate specific neuropathological entities.

Keywords: Alzheimer’s disease, behavioral variant frontotemporal dementia, cerebrospinal fluid, Lewy body dementia, limbic-predominant age-related TDP-43 encephalopathy, mild cognitive impairment, positron emission tomography, primary age-related tauopathy, subjective cognitive decline, suspected non-Alzheimer’s disease pathophysiology

DOI: 10.3233/JAD-240660

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1133-1136, 2024

Authors: Wang, Jiayu | Xu, Lisi | Chen, Xuemei | Wu, Jiajing | Chen, Yu | Feng, Ziqian | Dong, Li | Yao, Dezhong | Cai, Qingyan | Jian, Wei | Li, Hongyi | Duan, MingJun | Wang, Ziqi

Article Type: Research Article

Abstract: Background: Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer’s disease. Objective: To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints. Methods: Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer’s biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People’s Hospital of Chengdu (FPHC). …The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient’s cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed. Results: Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth. Conclusions: ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints. Show more

Keywords: Alzheimer’s disease, ApoB, lateral occipital cortex, memory complaints, sulcal depth

DOI: 10.3233/JAD-230863

Citation: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1137-1150, 2024