Journal of Alzheimer's Disease - Volume 82, issue 3

Authors: de la Torre, Jack C. | Gonzalez-Lima, Francisco

Article Type: Editorial

DOI: 10.3233/JAD-210736

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 881-882, 2021

Authors: Toniolo, Sofia | Scarioni, Marta | Di Lorenzo, Francesco | Hort, Jakub | Georges, Jean | Tomic, Svetlana | Nobili, Flavio | Frederiksen, Kristian Steen | the Management Group of the EAN Dementia and Cognitive Disorders Scientific Panel

Article Type: Review Article

Abstract: Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18 F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. …Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers. Show more

Keywords: Alzheimer’s disease, cognition, COVID-19, dementia, SARS-CoV-2

DOI: 10.3233/JAD-210335

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 883-898, 2021

Authors: Ancelin, Marie-Laure | Norton, Joanna | Scali, Jacqueline | Ritchie, Karen | Chaudieu, Isabelle | Ryan, Joanne

Article Type: Short Communication

Abstract: Diurnal salivary cortisol was measured in 334 older adults without dementia, at four times on two separate days, under quiet and stressful conditions. In multivariate Cox proportional hazard models, higher global diurnal cortisol secretion was associated with incident dementia (HR = 1.09 [1.02–1.15] per one-unit increase in cortisol measure, p  = 0.007) and Alzheimer’s disease (HR = 1.12 [1.04–1.21], p  = 0.003) over a mean (SD) of 8.1 (4.0) years, independent of potential confounders and stressful conditions. Individuals with incident dementia had a slower rate of cortisol elimination under non-stressful conditions, reflected by higher cortisol levels in the evening, and an abnormal response to stress (blunted …evening stress response). Show more

Keywords: Cortisol, dementia, hypothalamic-pituitary-adrenal axis, prospective study, stress

DOI: 10.3233/JAD-210389

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 899-904, 2021

Authors: Malcorra, Bárbara Luzia Covatti | Mota, Natália Bezerra | Weissheimer, Janaina | Schilling, Lucas Porcello | Wilson, Maximiliano Agustin | Hübner, Lilian Cristine

Article Type: Short Communication

Abstract: Connected speech is an everyday activity. We aimed to investigate whether connected speech can differentiate oral narrative production between adults with Alzheimer’s disease (AD; n  = 24) and cognitively healthy older adults (n  = 48). We used graph attributes analysis to represent connected speech. Participants produced oral narratives and performed semantic, episodic, and working memory tasks. AD patients produced less connected narratives than cognitively healthy older adults. Connectedness was associated with semantic memory in AD and with episodic memory in controls. Word-graphs connectedness represents a practical tool to assess cognitive impairment in AD patients.

Keywords: Alzheimer’s disease, cognitive decline, graph theory, natural language processing, semantic memory

DOI: 10.3233/JAD-210134

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 905-912, 2021

Authors: Pilotto, Andrea | Imarisio, Alberto | Carrarini, Claudia | Russo, Mirella | Masciocchi, Stefano | Gipponi, Stefano | Cottini, Elisabetta | Aarsland, Dag | Zetterberg, Henrik | Ashton, Nicholas J. | Hye, Abdul | Bonanni, Laura | Padovani, Alessandro

Article Type: Short Communication

Abstract: Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from …the early stages of DLB. Show more

Keywords: Biomarkers, cognitive progression, dementia with Lewy bodies, neurofilament light chain

DOI: 10.3233/JAD-210342

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 913-919, 2021

Authors: Chen, X. Richard | Shao, Yongzhao | Sadowski, Martin J. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: APOE ɛ 4 allele carriers present with an increased risk for late-onset Alzheimer’s disease (AD), show cognitive symptoms at an earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ 4 allele controls the rate of disease progression. Objective: To determine the effects of the ɛ 4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD. Methods: A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain …volumetric data of 73 ɛ 3/ɛ 3, 99 ɛ 3/ɛ 4, and 39 ɛ 4/ɛ 4 Alzheimer’s Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia. Results: ɛ 4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ 4 allele-dose effects after dementia transition but not during MCI. The ɛ 4 effect was more prevalent in younger participants and in females. ɛ 4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI. Conclusion: Possession of the ɛ 4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design. Show more

Keywords: Alzheimer disease, APOE, cognitive decline, linear mixed model, MRI

DOI: 10.3233/JAD-210434

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 921-937, 2021

Authors: González-Alcaide, Gregorio | Fernández-Ríos, Mercedes | Redolat, Rosa | Serra, Emilia

Article Type: Research Article

Abstract: Background: The study of emotion recognition could be crucial for detecting alterations in certain cognitive areas or as an early sign of neurological disorders. Objective: The main objective of the study is to characterize research development on emotion recognition, identifying the intellectual structure that supports this area of knowledge, and the main lines of research attracting investigators’ interest. Methods: We identified publications on emotion recognition and dementia included in the Web of Science Core Collection, analyzing the scientific output and main disciplines involved in generating knowledge in the area. A co-citation analysis and an analysis of …the bibliographic coupling between the retrieved documents elucidated the thematic orientations of the research and the reference works that constitute the foundation for development in the field. Results: A total of 345 documents, with 24,282 bibliographic references between them, were included. This is an emerging research area, attracting the interest of investigators in Neurosciences, Psychology, Clinical Neurology, and Psychiatry, among other disciplines. Four prominent topic areas were identified, linked to frontotemporal dementia, autism spectrum disorders, Alzheimer’s disease, and Parkinson’s and Huntington disease. Many recent papers focus on the detection of mild cognitive impairment. Conclusion: Impaired emotion recognition may be a key sign facilitating the diagnosis and early treatment of different neurodegenerative diseases as well as for triggering the necessary provision of social and family support, explaining the growing research interest in this area. Show more

Keywords: Alzheimer’s disease, bibliometrics, dementia, emotions, facial recognition, knowledge discovery

DOI: 10.3233/JAD-210096

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 939-950, 2021

Authors: Darmanthé, Nicolas | Tabatabaei-Jafari, Hossein | Cherbuin, Nicolas | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Individuals with mild cognitive impairment (MCI) are at high risk of progression to Alzheimer’s disease (AD) dementia, but some remain stable. There is a need to identify those at higher risk of progression to improve patient management and outcomes. Objective: To evaluate the trajectory of plasma neurofilament light chain (pNFL) prior to progression from MCI to AD dementia, the performance of pNFL, in combination with the Mini-Mental State Examination (MMSE), as a predictor of progression from MCI to AD dementia and to inform clinicians on the use of pNFL as a predictive biomarker. Methods: Participants …(n  = 440) with MCI and longitudinal follow-up (mean = 4.2 years) from the AD Neuroimaging Initiative dataset were included. pNFL as a marker for neurodegeneration and the MMSE as a cognitive measure were investigated as simple/practical predictors of progression. The risk of progressing from MCI to AD dementia associated with pNFL and MMSE scores was assessed using Cox and logistic regression models. Results: The current risk of progression to AD dementia was 37%higher in individuals with high pNFL (> 56 ng/L) compared to those with average pNFL (≤40 ng/L). A combination of baseline pNFL and MMSE could differentiate those who progressed within 5 years (AUC = 0.75) from stable individuals. Including change in MMSE over 6-12 months further improved the model (AUC = 0.84). Conclusion: Our findings reveal that combining pNFL with a simple dementia screener (MMSE) can reliably predict whether a person with MCI is likely to progress to AD dementia within 5 years. Show more

Keywords: Alzheimer’s disease, clinical progression, mild cognitive impairment, neurofilament, plasma biomarkers

DOI: 10.3233/JAD-210092

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 951-964, 2021

Authors: Kvello-Alme, Marte | Bråthen, Geir | White, Linda R. | Sando, Sigrid Botne

Article Type: Research Article

Abstract: Background: Young onset dementia is associated with a longer time to diagnosis compared to late onset dementia. Earlier publications have indicated that atypical presentation is a key contributing factor to the diagnostic delay. Our hypothesis was that even the most common presentation of Alzheimer’s disease is associated with a substantial diagnostic delay in patients < 65 years. Objective: To determine the time to diagnosis, and time lags in the diagnostic pathway in typical young onset Alzheimer’s disease in central Norway. Methods: The main sources of patients were the databases at the Department of Neurology, University Hospital of Trondheim …(St. Olav’s Hospital), and Department of Psychiatry, Levanger Hospital. Other sources included key persons in the communities, collaborating hospital departments examining patients with suspected cognitive impairment, and review of hospital records of all three hospitals in the area. Information on the time lags, and the clinical assessment, including the use of biomarkers, was collected from hospital notes. Caregivers were interviewed by telephone. Results: Time from first symptom to diagnosis in typical young onset Alzheimer’s disease was 5.5 years (n  = 223, SD 2.8). Time from onset to contact with healthcare services (usually a general practitioner) was 3.4 years (SD 2.3). Time from contact with healthcare services to the first visit at a hospital was 10.3 months (SD 15.5). Time from first visit at a hospital to diagnosis was 14.8 months (SD 22.6). The analysis of cerebrospinal fluid core biomarkers was performed after 8.3 months (SD 20.9). Conclusion: Typical Alzheimer’s disease is associated with a substantial diagnostic delay in younger patients. Raising public awareness, and education of healthcare professionals on the aspects of young onset Alzheimer’s disease is warranted. CSF core biomarkers should be performed earlier in the hospital evaluation process. Show more

Keywords: Clinical characteristics, delayed diagnosis, diagnosis, early onset Alzheimer’s disease, early onset dementia, young onset dementia

DOI: 10.3233/JAD-210090

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 965-974, 2021

Authors: Yamada, Yosuke | Umegaki, Hiroyuki | Kinoshita, Fumie | Huang, Chi Hsien | Sugimoto, Taiki | Fujisawa, Chisato | Komiya, Hitoshi | Watanabe, Kazuhisa | Nagae, Masaaki | Kuzuya, Masafumi | Sakurai, Takashi

Article Type: Research Article

Abstract: Background: Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function. Objective: The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients. Methods: This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal …cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable. Results: Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p  = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (β= –2.790, p  < 0.001) or clinical diagnosis of dementia (β= –3.145, p  < 0.001). These results were similar for men and women. Conclusion: Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness. Show more

Keywords: Cognitive impairment, hand grip strength, homocysteine, sarcopenia

DOI: 10.3233/JAD-210083

Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 975-984, 2021