Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

AbstractIntroductionThis meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.MethodMEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.ResultsA total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.DiscussionCN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition

Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

10.1371/journal.pone.0023853PLoS ONE68

Surveillance of Broad-Spectrum Antibiotic Prescription in Singaporean Hospitals: A 5-Year Longitudinal Study

10.1371/journal.pone.0028751PLoS ONE612

Learning deficit in cognitively normal apoe ε4 carriers with low β-amyloid

Introduction: In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ–) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ–CNs. Methods: Aβ– CNs(n= 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT) over 6 days. Results: Aβ– ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non-carriers (d = 0.3). Rates of learning on the ORCA-LLT were significantly slower in Aβ– ε4 carriers compared to non-carriers (d = 1.2). Discussion: In Aβ– CNs,ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA-LLT. Alzheimer’s disease (AD)–related cognitive abnormalities can manifest before preclinical AD thresholds

Sensitivity of composite scores to amyloid burden in preclinical Alzheimer\u27s disease: Introducing the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults composite score

Introduction: Cognitive composite scores developed for preclinical Alzheimer\u27s disease (AD) often consist of multiple cognitive domains as they may provide greater sensitivity to detect β-amyloid (Aβ)-related cognitive decline than episodic memory (EM) composite scores alone. However, this has never been empirically tested. We compared the rate of cognitive decline associated with high Aβ (Aβ+) and very high Aβ (Aβ++) in cognitively normal (CN) older adults on three multidomain cognitive composite scores and one single-domain (EM) composite score. Methods: CN older adults (n = 423) underwent Aβ neuroimaging and completed neuropsychological assessments at baseline, and at 18-, 36-, 54-, and 72-month follow-ups. Four cognitive composite scores were computed: the ADCS-PACC (ADCS-Preclinical Alzheimer Cognitive Composite), ADCS-PACC without the inclusion of the mini-mental state examination (MMSE), an EM composite, and the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults (ZAVEN) composite. Results: Compared with Aβ+ CN older adults, Aβ++ CN older adults showed faster rates of decline across all cognitive composites, with the largest decline observed for ZAVEN composite (d = 1.07). Similarly, compared with Aβ- CN older adults, Aβ+ CN older adults also showed faster rates of cognitive decline, but only for the ADCS-PACC no MMSE (d = 0.43), EM (d = 0.53), and ZAVEN (d = 0.50) composites. Discussion: Aβ-related cognitive decline is best detected using validated neuropsychological instruments. Removal of the MMSE from the ADCS-PACC and replacing it with a test of executive function (verbal fluency; i.e., the ZAVEN) rendered this composite more sensitive even in detecting Aβ-related cognitive decline between Aβ+ and Aβ++ CN older adults

Aβ-related memory decline in APOE ϵ4 noncarriers: Implications for Alzheimer disease

Objective: As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN). Methods: CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Results: Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ϵ4 carriers than in Aβ+ CN ϵ4 noncarriers. No cognitive decline was evident in Aβ- CN ϵ4 carriers. Conclusions: In CN older adults, Aβ+ is associated with memory decline in ϵ4 noncarriers; however, the rate of this decline is much slower than that observed in ϵ4 carriers. These data indicate that the processes by which ϵ4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease. © 2016 American Academy of Neurology

Amyloid-related memory decline in preclinical Alzheimer\u27s disease in dependent on APOE ε4 and is detectable over 18-months

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 monthes, in 317 cognitively healthy (CN) older adults (47% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SC = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβwas unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer’s disease

Rates of age- and amyloid β-associated cortical atrophy in older adults with superior memory performance

Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid b (Ab) deposition (Ab1) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Ab-associated neurodegeneration. Methods: Neuropsychologically defined SuperAgers (n 5 172) and cognitively normal for age (n 5 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Ab status. Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Ab1. Rates of age- and Ab-associated atrophy did not differ between the groups on any measure. Ab2 individuals displayed the slowest rates of atrophy. Discussion: Maintenance of superior memory in late life does not reflect resistance to age- or Abassociated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Ab deposition (i.e. Ab2) displayed reduced rates of cortical atrophy

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal alzheimer\u27s disease: A preliminary study

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer\u27s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. Results: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401). Conclusions: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD

Revisiting the Color-Color Selection: Submillimeter and AGN Properties of NUV-r-J Selected Quiescent Galaxies

We examine the robustness of the color-color selection of quiescent galaxies (QGs) against contamination of dusty star-forming galaxies using the latest submillimeter data. We selected 18,304 QG candidates out to $z\sim$ 3 using the commonly adopted $NUV-r-J$ selection based on the high-quality multi-wavelength COSMOS2015 catalog. Using extremely deep 450 and 850 $\mu$m catalogs from the latest JCMT SCUBA-2 Large Programs, S2COSMOS, and STUDIES, as well as ALMA submillimeter, VLA 3 GHz, and $Spitzer$ MIPS 24 $\mu$m catalogs, we identified luminous dusty star-forming galaxies among the QG candidates. We also conducted stacking analyses in the SCUBA-2 450 and 850 $\mu$m images to look for less-luminous dusty galaxies among the QG candidates. By cross-matching to the 24 $\mu$m and 3 GHz data, we were able to identify a sub-group of "IR-radio-bright" QGs who possess a strong 450 and 850 $\mu$m stacking signal. The potential contamination of these luminous and less-luminous dusty galaxies accounts for approximately 10% of the color-selected QG candidates. In addition, there exists a spatial correlation between the luminous star-forming galaxies and the QGs at a $\lesssim60$ kpc scale. Finally, we found a high QG fraction among radio AGNs at $z<$ 1.5. Our data show a strong correlation between QGs and radio AGNs, which may suggest a connection between the quenching process and the radio-mode AGN feedback.Comment: This paper is accepted for publication on Ap