Journal of Alzheimer's Disease - Volume 84, issue 1

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 Aβ42 and Aβ40 ; Aβ42/40 ratio; neurofilaments (NFL); total tau (T-tau); and phosphorylated-tau181 (P-tau181). Higher and lower plasma baseline levels of P-tau181 and the Aβ42/40 ratio, respectively, showed consistently good prognostication of Aβ-PET brain accumulation. Only P-tau181 was shown to predict AD progression. Conclusion: In conclusion, the Aβ42/40 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. 84, no. 1, pp. 393-407, 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. 84, no. 1, pp. 409-418, 2021

Authors: Tarawneh, Hadeel Y. | Mulders, Wilhelmina H.A.M. | Sohrabi, Hamid R. | Martins, Ralph N. | Jayakody, Dona M.P.

Article Type: Research Article

Abstract: Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer’s disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. Methods: The search was performed on six major electronic databases (Ovid MEDLINE, OVID …EMBASE, PsycINFO, PubMed, Scopus, and CINAHL Plus). Articles identified prior to 7 May 2019 were considered for this review. A random effects meta-analysis and analysis of between study heterogeneity was conducted using the Comprehensive Meta-Analysis software. Results: The search identified 1,076 articles; 74 articles met the full inclusion criteria and were included in the systematic review, and 47 articles were included into the analyses. Pooled analysis suggests that AD participants can be differentiated from controls due to significant delays in ABR, N100, P200, N200, and P300 latencies. P300 amplitude was significantly smaller in AD participants compared to controls. P300 latencies differed significantly between MCI participants and controls based on the pooled analysis. Conclusion: The findings of this review indicate that some AERPs may be valuable biomarkers of AD. In conjunction with currently available clinical and neuropsychological assessments, AERPs can aid in screening and diagnosis of prodromal AD. Show more

Keywords: Alzheimer’s disease, cognitive function, event-related potentials, meta-analysis, mild cognitive impairment

DOI: 10.3233/JAD-210556

Citation: Journal of Alzheimer's Disease, vol. 84, no. 1, pp. 419-448, 2021

Authors: Doshi, Kinjal | Henderson, Stacey L. | Fan, Qianqian | Wong, Kian F. | 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. 84, no. 1, pp. 449-458, 2021

Article Type: Correction

DOI: 10.3233/JAD-219010

Citation: Journal of Alzheimer's Disease, vol. 84, no. 1, pp. 459-459, 2021