Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Cianflone, Alessandra | Coppola, Luigi | Mirabelli, Peppino | Salvatore, Marco

Article Type: Research Article

Abstract: Background: An amyloid-β (Aβ) positron emission tomography (Aβ-PET) scan of the human brain could lead to an early diagnosis of Alzheimer’s disease (AD) and estimate disease progression. However, Aβ-PET imaging is expensive, invasive, and rarely applicable to cognitively normal subjects at risk for dementia. The identification of blood biomarkers predictive of Aβ brain deposition could help the identification of subjects at risk for dementia and could be helpful for the prognosis of AD progression. Objective: This study aimed to analyze the prognostic accuracy of blood biomarkers in predicting Aβ-PET status along with progression toward AD. Methods: …In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched bibliographic databases from 2010 to 2020. The quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results: A total of 8 studies were retrieved. The prognostic accuracy of Aβ-PET status was calculated by obtaining ROCs for the following biomarkers: free, total, and bound Aβ 42 and Aβ 40 ; Aβ 42/40 ratio; neurofilaments (NFL); total tau (T-tau); and phosphorylated-Tau181 (P-tau181). Higher and lower plasma baseline levels of P-tau181 and the Aβ 42/40 ratio, respectively, showed consistently good prognostication of Aβ-PET brain accumulation. Only P-tau181 was shown to predict AD progression. Conclusion: In conclusion, the Aβ 42/40 ratio and plasma P-tau181 were shown to predict Aβ-PET status. Plasma P-tau181 could also be a preclinical biomarker for AD progression. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, mild cognitive impairment, preclinical Alzheimer’s disease, positron emission tomography, prognostic accuracy, sensitivity, specificity

DOI: 10.3233/JAD-210496

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2021

Authors: Mohr, Wiebke | Rädke, Anika | Afi, Adel | Edvardsson, David | Mühlichen, Franka | Platen, Moritz | Roes, Martina | Michalowsky, Bernhard | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: Person-centered care (PCC) is an important concept in many countries’ national guidelines and dementia plans. Key intervention categories, i.e., a taxonomy of person-centered (PC)-interventions, to provide person-centered dementia care, are difficult to identify from literature. Objective: This systematic review aimed to identify and categorize published PC-interventions into key intervention categories to guide the provision of person-centered dementia care. Methods: Conduct of this systematic review followed Cochrane guidelines. A search of the dimensions ‘Dementia’, ‘Person-Centered Care’, and ‘Intervention’ combined was performed in PubMed, EMBASE, and Web of Science. Study selection was based on 2-stage screening against …eligibility criteria, limited to controlled study designs. Information about interventions and outcomes was extracted into an “Effects Table”. The identified PC-interventions were categorized in intervention categories to provide person-centered dementia care. Results: Searches identified 1,806 records. 19 studies were included. These covered a range of psychosocial interventions, oftentimes multi-component interventions, which followed heterogeneous approaches. Studies were conducted in long-term care/hospital settings. Nine key intervention categories were identified: social contact, physical activities, cognitive training, sensory enhancement, daily living assistance, life history oriented emotional support, training and support for professional caregivers, environmental adjustments, and care organization. Conclusion: Our findings provide a current overview of published PC-interventions in dementia, which followed heterogeneous approaches under the PCC-concept. The heterogeneity made it challenging to identify a well-defined concept of PCC and common key intervention categories. An effectiveness-evaluation of “PC”-including “relationship-centered”-interventions may be valuable, to assess whether an explicit focus on relationships around PCC-interventions yields an added benefit. PROSPERO-ID: CRD42021225084. Show more

Keywords: Alzheimer’s disease, dementia, patient-centered care, patient-focused care, patient preferences, person-centered care, person-centered dementia care, person-centered interventions, psychosocial intervention

DOI: 10.3233/JAD-210647

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-24, 2021

Authors: Ferreira-Brito, Filipa | Ribeiro, Filipa | Aguiar de Sousa, Diana | Costa, João | Caneiras, Cátia | Carriço, Luís | Verdelhoa,

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) and dementia are associated with increased age. MCI is a clinical entity described as a transitional state between normal cognition and dementia. Video games (VGs) can potentially promote cognition and functional capacity since multiple cognitive domains are recruited during gameplay. However, there is still a lack of consensus regarding the efficacy of VGs as therapeutic tools, particularly in neurodegenerative diseases. Objective: We aimed to analyze the impact of VGs on cognition and functional capacity outcomes in MCI/dementia patients. Methods: We conducted a systematic review and meta-analysis study (PROSPERO [CRD42021229445]). PubMed, Web …of Science, Epistemonikos, CENTRAL, and EBSCO electronic databases were searched for RCT (2000-2021) that analyzed the impact of VGs on cognitive and functional capacity outcomes in MCI/dementia patients. Results: Nine studies were included (n  = 409 participants), and Risk of Bias (RoB2) and quality of evidence (GRADE) were assessed. Data regarding attention, memory/learning, visual working memory, executive functions, general cognition, functional capacity, quality of life were identified, and pooled analyses were conducted. An effect favoring VGs interventions was observed on Mini-Mental State Examination (MMSE) score (MD  = 1.64, 95%CI 0.60 to 2.69). Conclusion: Although promising, the effects observed should be interpreted with caution since serious methodological shortcomings were identified in the studies included. Nonetheless, the effect observed is higher than the minimum clinically important difference (1.4 points) established to MMSE. Future studies on the current topic urge. Recommendations for the design and conduction of cognitive RCT studies are presented. Show more

Keywords: Cognition, dementia, independent living, mhealth, mild cognitive impairment, telerehabilitation, video games

DOI: 10.3233/JAD-210545

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Rutten, Jeanine J.S. | van Kooten, Janine | van Loon, Anouk M. | van Buul, Laura W. | Joling, Karlijn J. | Smalbrugge, Martin | Hertogh, Cees M.P.M.

Article Type: Research Article

Abstract: Background: The COVID-19 pandemic has led to high mortality rates in nursing homes (NHs) in Europe. For adequate risk management and good prognostications, it is essential to identify mortality risk factors. Objective: This study aimed to determine whether previously identified risk factors for 30-day mortality in Dutch NH residents with COVID-19 are unique to COVID-19. Methods: In this cohort study, we included 1,294 NH residents with COVID-19 (cases) and 17,999 NH residents without COVID-19 (controls, from the pre-COVID-19 period). We used descriptive statistics and Cox proportional hazard models to compare mortality rates in residents with and …without COVID-19, categorized by risk factors. Results: Cases had a more than 18 times higher hazard of death within 30 days compared to controls (HR 18, 95%CI: 16–20). For residents with COVID-19, being male, having dementia, and having Parkinson’s disease (PD) were all associated with a higher 30-day mortality (HR 1.8 versus 1.3 versus 1.7). Being male was also associated with a higher mortality (HR 1.7) in the control group, whereas having dementia and PD were not. COVID-19 symptomatology was very similar for residents with and without dementia or PD, except for delirium and malaise which was more frequent in residents with dementia. Conclusion: Dementia and PD were significant additional risk factors for mortality in Dutch NH residents with COVID-19, whereas male gender was not unique to residents with COVID-19. The frailty of PD and dementia in NH residents with COVID-19 are relevant to consider in prognostication, communication, and care planning with residents and their families. Show more

Keywords: Coronavirus, dementia, long-term care facilities, Parkinson’s disease, SARS-CoV-2

DOI: 10.3233/JAD-210319

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Kootar, Scherazad | Huque, Md Hamidul | Arthur, Richard | Mortby, Moyra | Anstey, Kaarin J.

Article Type: Research Article

Abstract: Background: Findings on the associations between anxiety and cognitive decline are mixed and often confounded. Objective: We studied whether anxiety symptoms were associated with the risk of cognitive decline after adequate adjustment of confounding factors. Methods: Our study consists of 2,551 community-dwelling older adults recruited between the ages of 60–64 years and followed up for 12 years in the PATH Through Life cohort study. Anxiety symptoms were measured using the Goldberg Anxiety Scale (GAS; range 0–9). General cognitive function, episodic memory, working memory, verbal intelligence, processing speed, and psychomotor speed were measured. Multilevel analyses were carried …out to investigate the association between anxiety symptoms and cognitive decline over 12 years, taking into account confounding variables. Results: We did not find a significant association between baseline anxiety symptoms and cognitive decline over 12 years. Although some associations between anxiety symptoms with psychomotor speed (β= –0.04, 99%CI: –0.08, 0.00) and processing speed (β= –0.27, 99%CI: –0.48, –0.07) were found, these were attenuated after adjusting for depression. We also did not find an association between cumulative anxiety and decline in cognitive performance. Conclusion: In this sample of cognitively healthy men and women aged 60 years and above, anxiety symptoms were not associated with the risk of cognitive decline. Long follow-up study time, appropriate selection of confounding factors, and estimating the effect of cumulative anxiety are important to establish the association between anxiety and cognitive symptoms. Show more

Keywords: Anxiety, anxiolytics, cognitive decline, depression, longitudinal study

DOI: 10.3233/JAD-210282

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Yamada, Yasunori | Shinkawa, Kaoru | Kobayashi, Masatomo | Caggiano, Vittorio | Nemoto, Miyuki | Nemoto, Kiyotaka | Arai, Tetsuaki

Article Type: Research Article

Abstract: Background: Gait, speech, and drawing behaviors have been shown to be sensitive to the diagnosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, previous studies focused on only analyzing individual behavioral modalities, although these studies suggested that each of these modalities may capture different profiles of cognitive impairments associated with AD. Objective: We aimed to investigate if combining behavioral data of gait, speech, and drawing can improve classification performance compared with the use of individual modality and if each of these behavioral data can be associated with different cognitive and clinical measures for the diagnosis of …AD and MCI. Methods: Behavioral data of gait, speech, and drawing were acquired from 118 AD, MCI, and cognitively normal (CN) participants. Results: Combining all three behavioral modalities achieved 93.0%accuracy for classifying AD, MCI, and CN, and only 81.9%when using the best individual behavioral modality. Each of these behavioral modalities was statistically significantly associated with different cognitive and clinical measures for diagnosing AD and MCI. Conclusion: Our findings indicate that these behaviors provide different and complementary information about cognitive impairments such that classification of AD and MCI is superior to using either in isolation. Show more

Keywords: Drawing, gait analysis, handwriting, machine learning, speech, voice, walking

DOI: 10.3233/JAD-210684

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Wang, Quan | Su, Ning | Huang, Jin | Liang, Xinyu | Yuan, Jing | Yao, Ming | Zhou, Li-Xin | Jin, Zheng-Yu | Zhang, Shu-Yang | Cui, Li-Ying | Gong, Gaolang | Tian, Feng | Zhu, Yi-Cheng | Ni, Jun

Article Type: Research Article

Abstract: Background: Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). Objective: We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. Methods: Participants (n  = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive …Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. Results: For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (β= 0.034, p  = 0.0062) and MoCA score (β= 0.034, p  = 0.0174), and negatively associated with TMT-A and TMT-B completion time (β= –2.319, p  = 0.0002; β= –2.827, p  = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (β= 17.241, p  = 0.0028). Conclusion: In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury. Show more

Keywords: Brain volume, cerebral small vessel disease, cognition, gray matter, magnetic resonance imaging, white matter

DOI: 10.3233/JAD-210367

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Wei,, Shan | Shang, Suhang | Dang, Liangjun | Gao, Fan | Gao, Yao | Gao, Ling | Chen, Chen | Huo, Kang | Wang, Jingyi | Wang, Jin | Qu, Qiumin

Article Type: Research Article

Abstract: Background: Studies have found that blood lipids are associated with plasma amyloid-β (Aβ) levels, but the underlying mechanism is still unclear. Two Aβ transporters, soluble form of low-density lipoprotein receptor related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE), are crucial in peripheral Aβ transport. Objective: The aim was to investigate the effects of lipids on the relationships between plasma Aβ and transporter levels. Methods: This study included 1,436 adults aged 40 to 88 years old. Blood Aβ, sLRP1, sRAGE, and lipid levels were measured. Univariate and multivariate analyses were used to analyze …the relationships between lipids and plasma Aβ, sLRP1, and sRAGE. Results: After adjusting for all possible covariates, high-density lipoprotein (HDL-c) was positively associated with plasma Aβ 42 and sRAGE (β= 6.158, p  = 0.049; β= 121.156, p  <  0.001, respectively), while triglyceride (TG) was negatively associated with plasma Aβ 40 , Aβ 42 , and sRAGE (β= –48.389, p  = 0.017; β= –11.142, p  = 0.020; β= –147.937, p  = 0.003, respectively). Additionally, positive correlations were found between plasma Aβ and sRAGE in the normal TG (Aβ 40 : β= 0.034, p  = 0.005; Aβ 42 : β= 0.010, p  = 0.001) and HDL-c groups (Aβ 40 : β= 0.023, p  = 0.033; Aβ 42 : β= 0.008, p  = 0.002) but not in the high TG and low HDL-c groups. Conclusion: Abnormal levels of TG and HDL-c are associated with decreased Aβ and sRAGE levels. Positive correlations between plasma Aβ and sRAGE were only found in the normal TG and HDL-c groups but not in the high TG and low HDL-c groups. These results indicated that dyslipidemia contributing to plasma Aβ levels might also be involved in peripheral Aβ clearance. Show more

Keywords: Alzheimer’s disease, amyloid-β, high density lipoprotein, soluble low-density lipoprotein receptor-related protein-1, soluble receptor of advanced glycation end products, triglyceride

DOI: 10.3233/JAD-210405

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Sogorb-Esteve, Aitana | Colas, Romain A. | Dalli, Jesmond | Rohrer, Jonathan D.

Article Type: Research Article

Abstract: Background: The pathophysiology of frontotemporal dementia (FTD) is poorly understood but recent studies implicate neuroinflammation as an important factor. However, little is known so far about the role of the resolution pathway, the response to inflammation that allows tissue to return to a homeostatic state. Objective: We aimed to measure the concentrations of lipid mediators including specialized proresolving mediators (SPMs) and proinflammatory eicosanoids in the cerebrospinal fluid (CSF) of people with FTD. Methods: 15 people with genetic FTD (5 with C9orf72 expansions, 5 with GRN mutations, and 5 with MAPT mutations) were recruited …to the study along with 15 age- and sex-matched healthy controls. Targeted liquid chromatography-tandem mass spectrometry techniques were used to measure the CSF concentrations of lipid mediators in the docosahexaenoic acid (DHA), n-3 docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid (AA) metabolomes. Results: Only the C9orf72 expansion carriers had higher concentrations of SPMs (DHA-derived maresins and DHA-derived resolvins) compared with controls. In contrast, GRN and MAPT mutation carriers had normal concentrations of SPMs but significantly higher concentrations of the proinflammatory AA-derived leukotrienes and AA-derived thromboxane compared with controls. Additionally, the C9orf72 expansion carriers also had significantly higher concentrations of AA-derived leukotrienes. Conclusion: This initial pilot study of lipid mediators provides a window into a novel biological pathway not previously investigated in FTD, showing differential patterns of alterations between those with C9orf72 expansions (where SPMs are higher) and GRN and MAPT mutations (where only proinflammatory eicosanoids are higher). Show more

Keywords: C9orf72, frontotemporal dementia, lipid mediators, neuroinflammation, progranulin, tau.

DOI: 10.3233/JAD-210559

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2021

Authors: Doshi, Kinjal | Henderson, Stacey Lee | Fan, Qianqian | Wong, Kian Foong | Lim, Julian

Article Type: Research Article

Abstract: Background: Current pharmacological and behavioral treatment options for mild cognitive impairment (MCI) are limited, motivating a search for alternative therapies that might slow the progression of cognitive decline. Objective: We investigated the effectiveness of a cognition-focused mindfulness-based intervention. Methods: An open-label, three arm randomized controlled trial was conducted at a public tertiary medical center. Older persons (ages 45–75; N = 76) diagnosed with MCI were recruited and randomized into either Mindfulness-based training (MBT), cognitive rehabilitation therapy (CRT), or treatment as usual (TAU). Participants in the intervention arms received 8 weekly 2-h sessions delivered in a group setting and …engaged in home practice. Primary outcomes measures included changes in index scores for attention, immediate memory, and delayed memory as measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Depression was a secondary outcome. Results: Using intent-to-treat analysis, we found that participants receiving MBT showed significant improvements in global cognition (d = 0.26; [95%CI 0.03–0.56]) and delayed memory (d = 0.36; [95%CI 0.17–0.57]), with significantly greater improvements in delayed memory than CRT (ηp 2  = 0.10). However, there was no benefit of MBT over TAU. No change in depression was observed in the MBT group. Reductions in depression were associated with improvements in cognitive functioning in the MBT group only. Conclusion: Our results suggest that a cognition-focused MBT did not improve cognitive functioning in MCI patients substantially more than spontaneous reversion rates, possibly as mood symptoms were not significantly alleviated in this group. Show more

Keywords: Cognition, depression, memory, mild cognitive impairment, mindfulness, neuropsychology

DOI: 10.3233/JAD-215035

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2021