C-13 Sex Differences in Cognitive and Neurobiological Markers of Alzheimer's Disease

2019 ◽  
Vol 34 (6) ◽  
pp. 1041-1042
Author(s):  
J O'Hara ◽  
D Norton ◽  
R Koscik ◽  
N Lambrou ◽  
M Wyman ◽  
...  

Abstract Objective Previous work has demonstrated that intra-individual cognitive variability (IICV) has predictive power similar to traditional Alzheimer’s disease (AD) biomarkers, such as CSF or hippocampal volume (HV) loss. Genetic factors, such as sex, have been identified as predictors of cognitive decline. Analysis of sex differences in IICV and other biomarkers may elucidate additional dimensions of this metric. Method Baseline neurocognitive test and neuroimaging data from 335 participants with ≥2 visits enrolled in the Wisconsin Alzheimer’s Disease Research Center Clinical Core were included. Z-scores were calculated comparing individual performance to group performance by test (Rey Auditory Verbal Learning Test (Learning and Delayed Recall), Trail Making Test (A and B), and either Boston Naming Test (BNT) or Multilingual Naming Test (MINT)). MINT scores were converted to BNT scores using the NACC Crosswalk Study. The standard deviation of z-scores across tests was calculated to determine IICV. Characteristics by sex were compared using Mann-Whitney and Fisher’s Exact tests. Spearman’s Rho was calculated to compare IICV and HV (relative to intercranial volume). Results At baseline (Table 1): (1) Males had more education than females; (2) females had both higher relative HV and IICV; and (3) in females, relative HV demonstrated a weak positive correlation with baseline IICV (Figure 1). Conclusions IICV has previously demonstrated potential as a cost-effective non-invasive marker of preclinical AD. In females, larger relative HV and its correlation with IICV may be due to differences in metabolic brain age or concurrent progression of HV and IICV through the AD process. Analyses of other biopsychosocial factors are needed.

2019 ◽  
Vol 34 (6) ◽  
pp. 1039-1040
Author(s):  
J O'Hara ◽  
D Norton ◽  
R Koscik ◽  
N Lambrou ◽  
M Wyman ◽  
...  

Abstract Objective Intra-Individual Cognitive Variability (IICV) previously demonstrated predictive power similar to AD biomarkers (i.e., CSF and hippocampal volume (HV) loss). Previous work suggested sex differences in relative HV and IICV. Additionally, IICV differs in whites and underrepresented racial groups (URG). Our objective was to analyze these sex differences in white and URG participants. Method Baseline neurocognitive test and neuroimaging data from 335 cognitively healthy participants with ≥2 visits enrolled in the Wisconsin ADRC Clinical Core were included. Z-scores were calculated comparing individual performance to group performance by test (Rey Auditory Verbal Learning Test (Learning and Delayed Recall), Trail Making Test (A and B), and either Boston Naming Test (BNT) or Multilingual Naming Test (MINT)). MINT scores were converted to BNT scores using the NACC Crosswalk Study. The standard deviation of z-scores across tests was calculated to determine IICV. Characteristics by race and sex were compared using Mann-Whitney, Fisher’s Exact, and Kruskal-Wallis tests. Spearman’s Rho was calculated to compare baseline IICV and relative HV. Results At baseline (Table 1), differences across racial groups in age, years of education, relative HV, and IICV were identified. Sex and racial group differences were identified (Table 2). A weak positive correlation between HV and IICV was seen in white females (Figure 1). Conclusions IICV has potential to become a cost-effective, non-invasive marker of preclinical AD. Again, correlation between HV and IICV was seen, but only in white females. Analyses suggest group differences between white and URG males and females. However, more data is needed to further explore these differences.


2020 ◽  
Author(s):  
Jianfeng Wu ◽  
Qunxi Dong ◽  
Jie Gui ◽  
Jie Zhang ◽  
Yi Su ◽  
...  

ABSTRACTBiomarker assisted preclinical/early detection and intervention in Alzheimer’s disease (AD) may be the key to therapeutic breakthroughs. One of the presymptomatic hallmarks of AD is the accumulation of beta-amyloid (Aβ) plaques in the human brain. However, current methods to detect Aβ pathology are either invasive (lumbar puncture) or quite costly and not widely available (amyloid PET). Our prior studies show that MRI-based hippocampal multivariate morphometry statistics (MMS) are an effective neurodegenerative biomarker for preclinical AD. Here we attempt to use MRI-MMS to make inferences regarding brain amyloid burden at the individual subject level. As MMS data has a larger dimension than the sample size, we propose a sparse coding algorithm, Patch Analysis-based Surface Correntropy-induced Sparse coding and max-pooling (PASCS-MP), to generate a low-dimensional representation of hippocampal morphometry for each individual subject. Then we apply these individual representations and a binary random forest classifier to predict brain Aβ positivity for each person. We test our method in two independent cohorts, 841 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 260 subjects from the Open Access Series of Imaging Studies (OASIS). Experimental results suggest that our proposed PASCS-MP method and MMS can discriminate Aβ positivity in people with mild cognitive impairment (MCI) (Accuracy (ACC)=0.89 (ADNI)) and in cognitively unimpaired (CU) individuals (ACC=0.79 (ADNI) and ACC=0.82 (OASIS)). These results compare favorably relative to measures derived from traditional algorithms, including hippocampal volume and surface area, shape measures based on spherical harmonics (SPHARM) and our prior Patch Analysis-based Surface Sparse-coding and Max-Pooling (PASS-MP) methods.


2017 ◽  
Vol 29 (11) ◽  
pp. 1825-1834 ◽  
Author(s):  
Yen Ying Lim ◽  
Stephanie Rainey-Smith ◽  
Yoon Lim ◽  
Simon M. Laws ◽  
Veer Gupta ◽  
...  

ABSTRACTBackground:The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.Methods:Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.Results:At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.Conclusion:While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.


2011 ◽  
Vol 23 (10) ◽  
pp. 1560-1568 ◽  
Author(s):  
Jung-Hae Youn ◽  
Maryse Siksou ◽  
R. Scott Mackin ◽  
Jung-Seok Choi ◽  
Jeanyung Chey ◽  
...  

ABSTRACTBackground: In Asia, where illiteracy rates are high, determining the degree to which neuropsychological measures can be used to identify cognitive impairment in illiterate elders is important. The aim of this study was to evaluate the effectiveness of using formal neuropsychological assessments to distinguish healthy illiterate elders from dementia patients.Methods: We compared the cognitive performance of healthy elders who were illiterate (illiterate NC, n = 25) with those who were literate (literate NC, n = 25), literate patients with mild Alzheimer's disease (literate AD, n = 25), and illiterate patients with mild AD (illiterate AD, n = 25). Neuropsychological measures included the Mini-Mental State Examination (MMSE), the verbal fluency test, the Boston naming test, the Rosen drawing test, and the verbal learning test.Results: In the between-group analyses, the scores on all tests, except verbal fluency and recognition memory, were lower for illiterate NC compared to the literate NC. The scores on the MMSE, Boston naming test, Rosen drawing test, and immediate free recall could not distinguish the illiterate NC from literate AD. However, the scores on all tests, except the Rosen drawing test, could distinguish illiterate NC from illiterate AD. ROC analyses showed the same pattern of results. In addition, age-, sex-, and education-matched cut-off scores of all tests, except immediate recall and delayed recall trials of the verbal learning test, showed good specificities in participants who were illiterate compared to those in participants who were literate.Conclusion: These findings suggest that the impact of literacy on neuropsychological test performance is an important aspect of cognitive evaluations for elders who are illiterate.


2020 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Arianne Y. Albert ◽  
Cindy K. Barha ◽  
Liisa A.M. Galea

ABSTRACTAlzheimer’s disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have worse neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however biological sex can interact with diagnosis (mild cognitive impairment (MCI) or AD) and APOE genotype (number of ε4 alleles), although there are discrepancies between studies. Using the ADNI database, we analysed the effect of sex and APOE genotype (number of ε4 alleles) and sex and diagnosis (cognitively normal (CN), MCI, AD) on cognition (memory and executive function), hippocampal volume, CSF amyloid beta, CSF tau and ptau. More males were diagnosed with MCI but there was no sex difference in those diagnosed with AD, suggesting the progression from CN, MCI to AD may be sex-specific. We found, consistent with some studies, that females had higher levels of CSF tau-pathology that was disproportionately affected by APOE genotype compared to males. These results suggest that sex and APOE genotype effects on AD biomarkers may influence sex differences in incidence and progression of MCI and AD. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Females had better memory (including verbal) scores than males, which may suggest a delay in the onset of cognitive decline or diagnosis.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica Z. K. Caldwell ◽  
Jeffrey L. Cummings ◽  
Sarah J. Banks ◽  
Sebastian Palmqvist ◽  
Oskar Hansson

Abstract Background We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau−) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau− CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume. Conclusions CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.


2020 ◽  
Vol 77 (2) ◽  
pp. 745-752
Author(s):  
Audrey Keleman ◽  
Julie K. Wisch ◽  
Rebecca M. Bollinger ◽  
Elizabeth A. Grant ◽  
Tammie L. Benzinger ◽  
...  

Background: Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results: Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. Conclusion: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.


2020 ◽  
Author(s):  
Wanting Liu ◽  
Lisa Wing Chi Au ◽  
Jill Abrigo ◽  
Yishan Luo ◽  
Adrian Wong ◽  
...  

Abstract Background: We aimed to validate the performance of an MRI-based machine learning derived Alzheimer’s Disease-resemblance atrophy index (AD-RAI) in detecting preclinical and prodromal AD. Methods: A total of 62 subjects (mild cognitive impairment [MCI]=25, cognitively unimpaired [CU]=37) underwent MRI, 11C- PIB, and 18F-T807 PET. We investigated the performance of AD-RAI at the pre-specified cutoff of ≥ 0.5 in detecting preclinical and prodromal AD and compared its performance with that of visual and volumetric hippocampal measures. Results: AD-RAI achieved the best metrics among all subjects (sensitivity 0.73, specificity 0.91, accuracy 87.10%) and among MCI subgroup (sensitivity 0.91, specificity 0.79, accuracy 84.00%) in detecting A+T+ subjects over other measures. Among CU subgroup, hippocampal volume (sensitivity 0.75, specificity 0.88, accuracy 86.49%) achieved a higher sensitivity than AD-RAI (sensitivity 0.25, specificity 0.97, accuracy 89.19%) in detecting preclinical AD.Conclusions: AD-RAI aids the detection of early AD, in particular at the prodromal stage.


2019 ◽  
Vol 75 (7) ◽  
pp. 1393-1402 ◽  
Author(s):  
Hossein Tabatabaei-Jafari ◽  
Marnie E Shaw ◽  
Erin Walsh ◽  
Nicolas Cherbuin

Abstract Objectives This study aimed to investigate the predictive value of cognitive/functional measures in combination with hippocampal volume (HCV) on the probability of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Methods The Rey Auditory Verbal Learning Test for immediate memory, Mini-Mental State Examination, a functional assessment for independent daily activities and Alzheimer’s Disease Assessment Scale were used as cognitive/functional measures and HCV as neuroimaging measure. Logistic regression and Cox proportional hazard analyses were used to explore the measures’ predictive values for AD conversion and time to conversion. Results The probability of conversion from MCI to AD was associated with cognitive function, but this was moderated by HCV: higher at lower HCV and lower at higher HCV. General cognitive/functional measures were less predictive than immediate memory in predicting time to conversion to AD at small HCVs. Conclusion Effectiveness of cognitive measures and subtle functional abnormality in predicting conversion from MCI to AD is dependent on HCV, thus combined evaluation should be considered. A combination of HCV and immediate memory appear to perform best in predicting time to conversion.


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