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Background: Episodic memory impairment is a widely known core clinical symptom of Alzheimer's disease (AD). However, it is still uncertain if it is possible to detect meaningful signs or changes in memory in the preclinical stage of AD due to their within‐normal‐range performance. In the current study, we investigated both verbal and visuospatial memory as markers to track the disease progression in the preclinical AD. Method: We selected cognitively normal (CN) participants from the Gwangju Alzheimer's Disease and Related Dementia Cohort in Korea. We included a group of CN individuals who showed a significant amyloid‐beta (aß) deposition, defined by amyloid PET, at baseline and completed at least two follow‐up evaluations. In the final analysis, we included 130 individuals in the preclinical stage of AD. Episodic memory measures were delayed recall scores from the Rey Complex Figure Test (RCFT_delayed) and Seoul Verbal Learning test (SVLT_delayed). We performed logistic regression analysis with stepwise selection to examine associations between memory tests and progression. Result: The mean follow‐up month was 36.21. Twenty‐one (16.2%) participants were converted to MCI (n = 19) or AD dementia (n = 2), while the rest stayed as CN. When both RCFT_delayed and SVLT_delayed at baseline were entered in the logistic regression model, only the RCFT_delayed was significantly associated with the progression (OR = 0.288; 95% CI, 0.138‐0.602; p = 0.001). When change scores were added to the model, RCFT_delayed at baseline (OR = 0.223; 95% CI, 0.101‐0.496; p < 0.001), RCFT_delayed change score (OR = 0.470; 95% CI, 0.258‐0.857; p = 0.014), and SVLT_delayed change score (OR = 0.523; 95% CI, 0.290‐0.942; p = 0.031), were significant. Conclusion: Our results suggest that visuospatial, not verbal, memory measures may play an important role in sensitively detecting the relevant sign of future progression in asymptomatic individuals. In terms of verbal memory, the longitudinal decline was associated with progression. Our study suggests that the inclusion of a visuospatial memory test and repeated evaluation can help to detect the earliest decline in the preclinical stages of AD. [ABSTRACT FROM AUTHOR]

Background: The hypothetical concept of cognitive reserve (CR) has been proposed to explain why someone can manage to function normally even in the presence of brain pathology. However, it still remains to be determined what components constitute such resilience against Alzheimer's disease (AD) pathology. In the current study we investigated the characteristics of cognitively normal (CN) elders with high CR. Method: We included CN participants from the Gwangju Alzheimer's Disease and Related Dementia Cohort in Korea. We selected a group of CN individuals who showed a significant amyloid‐beta (aß) deposition at baseline and stayed CN over the follow‐up period. They were defined as high CR group. For comparison purpose, individuals with a significant aß deposition at baseline but converted to MCI at follow‐up were also included. In the final analysis, 94 high CR group and 24 control group were included. Group comparisons in socio‐demographic, clinical and cognitive variables were performed using χ2 tests and ANOVA controlling for age, education, gender, and follow‐up month. Result: Mean follow‐up month were 43.37. There were no group differences in education, gender, socio‐economic status, family history of dementia or stroke, medical conditions, body mass index, subjective memory complaints, and instrumental activities of daily living. However, high CR group was younger and had shorter follow‐up period, therefore such variables were controlled when cognitive tests were compared. High CR group was more religious (p < 0.001), showed higher complexity in former job (p = 0.009), and higher level of executive functoning (Digit Dpan Backward, p = 0.012; Fluency test, p = 0.008; Boston Naming Test, p = 0.014; Trail Making Test part B, p = 0.017) than control group. There were no group differences in episodic memory tests and visuospatial abilities. Conclusion: Individuals with high CR could cope better with AD pathology. Many factors have been suggested to be associated with CR. Regarding cognitive process involved, our findings suggest that executive function plays an important role in constituting high CR. Preserved executive function may, at least in part, underlie CR. [ABSTRACT FROM AUTHOR]

Objectives: The present study investigated the characteristics of amnestic mild cognitive impairment (aMCI) in subjects with low brain amyloid-beta (Aβ) burden. Furthermore, the relationships between amyloid-independent cognitive decline and serum lipid profiles, particularly apolipoprotein A1 (APOA1), were evaluated.Design: Cross-sectional and longitudinal follow-up study.Setting: University hospital dementia clinic.Participants: 28 aMCI and 35 cognitive normal (CN) elderly.Measurements: The study measures included baseline assessments of the subjects' clinical characteristics, lipid profiles, and magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B (PiB) positron emission tomography scans. Based on PiB retention at baseline, the aMCI subjects were divided into low Aβ (aMCI-) and high Aβ (aMCI+) subgroups. All aMCI subjects were followed up over a 1-year period.Results: The aMCI- group had a longer duration of illness than did the aMCI+ group. None of the aMCI- subjects were diagnosed with Alzheimer disease (AD) dementia during the 1-year follow-up period, whereas 26.7% of aMCI+ subjects developed AD dementia. The aMCI- group also exhibited lower serum APOA1 levels compared with both the aMCI+ and CN groups. Additionally, lower serum APOA1 levels were associated with cognitive decline and brain atrophy independent of Aβ deposition and vascular burden.Conclusions: Patients with aMCI- likely exhibit different clinical and pathophysiological characteristics than patients with aMCI+. Additionally, APOA1 may be an important contributor underlying amyloid-independent neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a global health crisis on multiple levels. A major impediment to AD research is the availability of socio‐culturally and language appropriate study materials and instruments and inclusion of under‐represented minorities. To fulfill this need, we apply best practices and lessons learned to translate study materials for use in the Asian Cohort for Alzheimer's Disease's (ACAD) study of AD in Asian Americans and Asian Canadians (ASAC) with the overarching goal in inclusivity of these populations to better understand the etiology of AD. Method: Our multi‐stag translation process is guided by the World Health Organization's (WHO) process of translation (forward and reverse translation, consensus verification and reconciliation) to achieve parity with the English materials for our target groups (Chinese (simplified and traditional; Mandarin and Cantonese), Korean and Vietnamese). ACAD's collective experience partnering with aging Asian adults has revealed not only a language barrier, but also issues with socio‐cultural communication traits, and literal translations that stigmatize AD and dementia. Consequently, we have taken into account the varying perceptions and expressions of words in a social context. The translation process was implemented by a team of multi‐lingual researchers/clinicians/community leaders with extensive practical translation experience. Since language influences how a speaker views the world, we employed a cross‐section of translators and emphasized conceptual (vs. literal) culturally appropriate translations for the community. Results: To date, we have developed Asian language versions of ACAD documents (informed consent, data collection, community and social media outreach materials, website) for all our target groups and continue the process of beta‐testing our study materials (including the cognitive assessment instruments). Conclusion: The multi‐stage translation process accounts for distinctive Asian socio‐cultural‐language backgrounds, providing an important guideline for AD researchers to promote health literacy in the health and general community in an effort to reduce health disparities in underrepresented groups, like Asians. In order to ensure fidelity across languages, we will continue validating the original English version in Chinese, Korean, and Vietnamese versions in the ACAD study. [ABSTRACT FROM AUTHOR]

Background: It is known that cognitive reserve (CR) support resilience against the effects of brain pathology. However, it still remains to be elucidated what can be served as a proxy for the CR. In the current study we investigated whether particular functional brain features have protective effect for future cognitive decline. We also examined if the relationship is different according to amyloid‐beta (aß) positivity. Method: Functional MRI data, clinical and neuropsychological data, and follow‐up information were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. In the final analysis, 48 cognitively normal (CN) elderly and 46 elderly with mild cognitive impairment (MCI) were included. Cognitive decline was measured by mini mental status examination (MMSE) change score from baseline and the last follow‐up. Resting state function image data processing was carried out using FMRIB’s Software Library and Brain Connectivity Toolbox. Cox proportional hazards models were conducted to investigate the associations between several cognitive reserve proxies and future cognitive decline. In addition, the relationship was explored separately for aß positivity Result: Mean follow‐up month were 45.84 (50.33 for CN, 41.15 for MCI). Based on MMSE change score, 41 were identified as cognitively decliners. Among baseline functional brain network parameters (density, clustering coefficients, path length, and global efficiency) education, and American National Adult Reading Test (AMNART) error score, and 4 ADNI neuropsychological summary scores, global efficiency (HR=2.04, 95% CI 1.07‐3.91) and ADNI‐EF score (HR=0.41, 95% CI 0.26‐0.64) were significant in the Cox proportional hazard model (Figure1A). This association was observed only in aß positive group, whereas no significant association was found in aß negative group (Figure 1BC). Conclusion: Our findings indicate that higher global efficiency in functional brain network and better executive function could delay cognitive decline, especially in aß positive group. Cognitive reserve is to preserve cognitive function better in the presence of brain pathology. Our study preliminary suggest that higher brain efficiency could play a key role in cognitive reserve in elders. [ABSTRACT FROM AUTHOR]

Background: Given that dementia prevalence is getting higher around the world, it is important to make a prognosis about clinical progression after dementia diagnosis. Brain reserve theory suggests that greater reserve supports for functional adaptation to clinical progression in neurodegeneration. Therefore, we examined if reserve proxies at baseline were associated with clinical progression among Alzheimer’s disease dementia (ADD). Method: We selected ADD data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Composite FDG‐PET ROIs (angular gyri, posterior cingulate, and inferior temporal gyri; FDG ROIs), structural MRI volumes for hippocampus, entohinal, and intracranial volume (ICV), American National Adult Reading Test (AMNART) error score, functional activities questionnaire (FAQ), mini mental status examination (MMSE), and other clinical and neuropsychological data, and follow‐up data were downloaded. Clinical progression was measured by change score of clinical dementia rating sum of box (CDR SB change) between baseline and the last follow‐up. Cox proportional hazards models were conducted to investigate the associations between reserve proxies and further progression with covariates of age, gender, and MMSE. Result: We included 120 patients with ADD at baseline. Mean follow‐up month were 11.42 (5.82, range 6∼24month). Based on CDR SB change, 87 were identified as progression group, while 33 were stable group. At baseline, there were no significant group difference in demographic variables, follow‐up month, CDR SB, FDG ROIs, MRI volumes, distribution of APOE ε4 and Aß positive. However, progression group showed lower performance in AMNART and some neuropsychological tests. Among reserve proxies (education, AMNART, FDG ROIs, ICV, FAQ), FDG ROIs (HR=2.209, p=0.002, 95% CI 1.339‐3.643) was significant in the Cox proportional hazard model. This association was observed only in lager ICV group (HR=4.628, p=0.001, 95% CI 1.810‐11.837), whereas no significant association was found in smaller ICV group. Conclusion: Our findings indicate that relatively preserved brain metabolism may slow a rate of clinical progression in ADD, particularly in greater ICV group. In addition to ICV, which is widely used proxy for brain reserve, glucose brain metabolism could play a key role in functional compensation in the process of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: The aging of brain is a topic has been constantly studied. Particularly, the norms for the elderly are important in diagnosing degenerative brain diseases, but the aging brain of East Asians has not been fully studied yet. “Neuro I” is a brain image quantitative analysis system with a built‐in large‐scale normative database for East Asians to provide quantified clinical information on how different an individual patient is from normal people. The study aimed to investigate ethnic differences of cortical brain volumes in normal elderly people, and to determine whether the norms considering racial disparities could improve the accuracy of diagnosis. Method: Using Neuro I, cortical volumes were measured from brain magnetic resonance (MR) images of 1,686 cognitively normal elderly Koreans aged 59 to 89. For Caucasians, the brain images of 855 Caucasian‐Non‐Hispanic subjects were selected from the ADNI and OASIS datasets. The regression model predicting brain volumes were built using ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and scanner manufacturers as predictors. Based on the prediction model, the z‐scores of each individual were calculated. To validate the z‐score for diagnosis, 420 Alzheimer’s disease (AD) subjects of Koreans and Caucasians, and the same number of normal subjects were selected. The four validation groups divided by race and diagnosis were age‐ and sex‐matched using a propensity score matching method. Result: The models predicting cortical volumes had a considerate amount of explained variance (mean R2: 55.8%, range: 42.7%–77.5%). Ethnicity explained substantial variances for temporal and parietal lobes (mean R2: 5.6%, range: 4.2%–7.5%), comparable to age (mean R2: 3.3%, range: 2.0%–4.3%). Furthermore, the z score of each region based on the model with ethnicity as a predictor (AUCs =.75,.72,.67, and.67 for left and right temporal and left and right parietal lobes, respectively) improved the accuracy of AD diagnosis compared to the z score based on the model without ethnicity (AUCs =.62,.59,.55, and.57). Conclusion: Race or ethnicity should be considered for establishing the normative data in normal aging and AD diagnosis. [ABSTRACT FROM AUTHOR]