The human hippocampus and its subfield volume across age, sex and APOE e4 status

2020 ◽  
Author(s):  
Michele Veldsman ◽  
Lisa Nobis ◽  
Fidel Alfaro Almagro ◽  
Stephen Smith ◽  
Sanjay Manohar ◽  
...  
Keyword(s):  
Selective Vulnerability ◽  
Hippocampal Volume ◽  
Healthy Ageing ◽  
Sporadic Alzheimer’S Disease ◽  
Female Sex ◽  
Human Hippocampus ◽  
Two Factors ◽  
E4 Allele ◽  
Hippocampal Complex ◽  
Female Carriers

Abstract Female sex, age and carriage of the APOE e4 allele are the greatest risk factors for sporadic Alzheimer's disease (AD). The hippocampus has a selective vulnerability to atrophy in ageing that may be accelerated in AD, including in those with increased genetic risk of AD. Within the hippocampal complex, subfields represent cytoarchitectonic and connectivity based divisions. The change in global hippocampal and subfield volume associated with sex, age and APOE e4 status in healthy ageing have not yet been established despite their potential to provide a sensitive biomarker of future vulnerability to AD. Here, we examined non-linear age, sex and APOE effects, and their interactions, on hippocampal and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing individuals. Hippocampal volume showed a marked reduction in APOE e4/e4 female carriers after age 65. Volume was lower in homozygous e4 individuals in specific subfields including the presubiculum, subiculum head, CA1 body, CA3 head and CA4. The findings demonstrate that in healthy ageing, two factors - female sex and APOE e4 status - confer selective vulnerability of specific hippocampal subfields to volume loss.

scholarly journals The human hippocampus and its subfield volumes across age, sex and APOE e4 status

2020 ◽  
Author(s):  
Michele Veldsman ◽  
Lisa Nobis ◽  
Fidel Alfaro-Almagro ◽  
Sanjay Manohar ◽  
Masud Husain
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Structures ◽  
Selective Vulnerability ◽  
Hippocampal Volume ◽  
Healthy Ageing ◽  
Female Sex ◽  
Model Free ◽  
Cornu Ammonis ◽  
Window Approach

Abstract Female sex, age and carriage of the APOE e4 allele are the greatest risk factors for sporadic Alzheimer’s disease. The hippocampus has a selective vulnerability to atrophy in ageing that may be accelerated in Alzheimer’s disease, including in those with increased genetic risk of the disease, years before onset. Within the hippocampal complex, subfields represent cytoarchitectonic and connectivity based divisions. Variation in global hippocampal and subfield volume associated with sex, age and APOE e4 status has the potential to provide a sensitive biomarker of future vulnerability to Alzheimer’s disease. Here, we examined non-linear age, sex and APOE effects, and their interactions, on hippocampal and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing individuals. FMRIB Software Library (FSL) derived estimates of total hippocampal volume and Freesurfer derived estimates hippocampal subfield volume were estimated. A model-free, sliding window approach was implemented that does not assume a linear relationship between age and subfield volume. The annualised percentage of subfield volume change was calculated to investigate associations with age, sex and APOE e4 homozygosity. Hippocampal volume showed a marked reduction in APOE e4/e4 female carriers after age 65. Volume was lower in homozygous e4 individuals in specific subfields including the presubiculum, subiculum head, cornu ammonis 1 body, cornu ammonis 3 head and cornu ammonis 4. Nearby brain structures in medial temporal and subcortical regions did not show the same age, sex and APOE interactions, suggesting selective vulnerability of the hippocampus and its subfields. The findings demonstrate that in healthy ageing, two factors—female sex and APOE e4 status—confer selective vulnerability of specific hippocampal subfields to volume loss.

scholarly journals Predicting time to dementia using a quantitative template of disease progression

2018 ◽  
Author(s):  
Bilgel Murat ◽  
Bruno M. Jedynak
Keyword(s):  
Verbal Memory ◽  
Hippocampal Volume ◽  
Onset Age ◽  
Sporadic Alzheimer’S Disease ◽  
Individual Level ◽  
History Of ◽  
Longitudinal Biomarker ◽  
T Tau ◽  
Dementia Onset

AbstractIntroductionCharacterization of longitudinal trajectories of biomarkers implicated in sporadic Alzheimer’s disease (AD) in decades prior to clinical diagnosis is important for disease prevention and monitoring.MethodsWe used a multivariate Bayesian model to temporally align 1369 AD Neuroimaging Initiative participants based on the similarity of their longitudinal biomarker measures and estimated a quantitative template of the temporal evolution cerebrospinal fluid (CSF) Aβ1-42, p-tau181p, and t-tau, hippocampal volume, brain glucose metabolism, and cognitive measurements. We computed biomarker trajectories as a function of time to AD dementia, and predicted AD dementia onset age in a disjoint sample.ResultsQuantitative template showed early changes in verbal memory, CSF Aβ1-42 and p-tau181p, and hippocampal volume. Mean error in predicted AD dementia onset age was < 1.5 years.DiscussionOur method provides a quantitative approach for characterizing the natural history of AD starting at preclinical stages despite the lack of individual-level longitudinal data spanning the entire disease timeline.

scholarly journals Examining Sex Differences in Markers of Cognition and Neurodegeneration in Autosomal Dominant Alzheimer’s Disease: Preliminary Findings from the Colombian Alzheimer’s Prevention Initiative Biomarker Study

2020 ◽  
Vol 77 (4) ◽  
pp. 1743-1753
Author(s):  
Clara Vila-Castelar ◽  
Edmarie Guzmán-Vélez ◽  
Enmanuelle Pardilla-Delgado ◽  
Rachel F. Buckley ◽  
Yamile Bocanegra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Sex Differences ◽  
Autosomal Dominant ◽  
Volume Ratio ◽  
Word List ◽  
Hippocampal Volume ◽  
Delayed Recall ◽  
List Learning ◽  
Age Range ◽  
Female Carriers

Background: Growing evidence suggests that there may be a sex-specific biological risk for Alzheimer’s disease (AD). Individuals with autosomal dominant AD due to a mutation (E280A) in Presenilin-1 (PSEN1) are genetically determined to develop early-onset dementia and thus, have few age-related risk factors for AD that are known to vary by sex (i.e., cardiovascular disease, menopause, life expectancy). Objective: Investigate sex differences in markers of cognition and neurodegeneration in autosomal dominant AD. Methods: We conducted a retrospective study in 19 cognitively-unimpaired PSEN1 mutation carriers (age range 20–44; 11 females), 11 symptomatic carriers (age range 42–56; 8 females), and 23 matched non-carriers family members (age range 20–50; 13 females). We examined hippocampal volume ratio, CERAD Total Score, and CERAD Word List (i.e., Learning, Delayed Recall, and Recognition). Mann-Whitney U tests, Spearman correlations and regression models were conducted. Results: There were no differential associations between age, CERAD Total Score, CERAD Word List–Learning, Delayed Recall, Recognition, and hippocampal volume ratio in male and female carriers and non-carriers. Cognitively-unimpaired female carriers showed better CERAD Total scores and CERAD Word List-Learning than cognitively-unimpaired male carriers, despite having similar hippocampal volume ratios. The interaction of sex and hippocampal volume ratio did not predict cognitive performance across groups. Conclusion: Our preliminary findings suggest that cognitively-unimpaired female carriers showed a verbal memory reserve, and as disease progresses, female carriers did not exhibit a cognitive susceptibility to AD-related neurodegeneration. Future studies with larger samples of autosomal dominant AD are warranted to further understand sex differences in AD-related clinical and pathological markers.

scholarly journals Protein Expression of Alzheimer's disease‐ and Reduced Hippocampal Volume‐ Risk Loci in Human Hippocampus

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Stephanie Adams ◽  
Tim Norman ◽  
Kathy Tilton ◽  
Sudha Seshadri ◽  
Ivana Delalle
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Expression ◽  
Hippocampal Volume ◽  
Human Hippocampus

scholarly journals Clinical and biomarker changes in sporadic Alzheimer’s disease

2020 ◽  
Author(s):  
Junjie Zhuo ◽  
Yuanchao Zhang ◽  
Bing Liu ◽  
Yong Liu ◽  
Xiaoqing Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Hippocampal Volume ◽  
Sporadic Alzheimer’S Disease ◽  
Dynamic Changes ◽  
Linear Change ◽  
Clinical Profiles ◽  
Annual Changes ◽  
Clinical Measures

AbstractIMPORTANCEThe dynamic changes of biomarkers and clinical profiles in sporadic Alzheimer’s disease (SAD) are poorly understood.OBJECTIVETo evaluate the impact of amyloid-β (Aβ) biomarkers on SAD by measuring the dynamic changes in biomarkers and clinical profiles in the progression of SAD.DESIGN AND SETTINGThis retrospective and longitudinal study analyzed clinical and biomarker data from 665 participants (mean follow-up 4.90 ± 2.83 years) from a subset of the AD Neuroimaging Initiative (ADNI) participants collected from August 2005 to December 2018. By aligning the timing of the changes in the various biomarkers with the stable normal cognition (CN) baseline and mild cognitive impairment (MCI) or AD onset timepoints, we combined data from the stable CN, CN conversion to MCI (CN2MCI), and MCI conversion to AD (MCI2AD) groups to identify the trajectories associated with the progression of AD.PARTICIPANTSThe participants were 294 CN, 69 CN2MCI, 300 MCI2AD, and 24 who converted from CN to MCI to AD (CN2MCI2AD) (of whom 22 were also included in the CN2MCI).EXPOSURESAmyloid-β measured by florbetapir positron emission tomography (PET) or cerebrospinal fluid assay of amyloid-β (CSF Aβ42).MAIN OUTCOMES AND MEASURESThe measures included the 13-item cognitive subscale of the AD Assessment Scale (ADAS13, as a clinical measure), hippocampal volume, and the fluorodeoxyglucose (FDG) PET standardized uptake value ratio (SUVR).RESULTSThe CN, CN2MCI, and MCI2AD subgroups’ median (interquartile range [IQR]) annual changes in ADAS13 were (0.388 [−0.278, 0.818], 1.000 [0.239, 2.330], and 3.388 [1.750, 6.169]). The annual changes in hippocampal volume for each group were (−0.005 %ICV [−0.011, −0.001], −0.006 %ICV [−0.012, −0.002], and −0.014 %ICV [−0.021, −0.009]). The annual changes in FDG PET SUVR for each group were (−0.011 [−0.030, 0.010], −0.027 [−0.056, −0.012], and −0.039 [−0.063, 0.014]). Changes in the amyloid biomarkers were inconsistent with clinical profile changes. The annual changes in CSF Aβ42 for each group were (−1.500 pg/ml [−6.000, 4.000], −2.200 [−5.667, 4.000], and −2.000 [−7.000, 2.650]) and in Aβ PET SUVR for each group were (0.004 [−0.002, 0.012], 0.004 [−0.001,0.011], and 0.005 [−0.006, 0.014]). During the stable CN and CN2MCI stages, subjects with elevated and those with normal amyloid showed no significant differences (likelihood ratio test, p < .01) in clinical measures, hippocampal volume, or FDG.CONCLUSIONS AND RELEVANCEHippocampal volume and FDG associated with clinical profiles impairment in the SAD progression. Aβ alone is not associated with clinical profiles, hippocampal volume, and FDG impairment in the preclinical stage of SAD.Key PointsQuestion: What is the role of amyloid-β in dynamic changes in biomarkers and clinical profiles in the progression of sporadic Alzheimer’s disease?Findings: The changes of the hippocampal volume and FDG that were consistent with the changes of the clinical profiles showed a non-linear change in the initial stage and an accelerated non-linear change during MCI2AD, changes in amyloid biomarkers were inconsistent with the clinical profile. Cognitively normal people with elevated or normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG.Meaning: Amyloid-β alone may not be used as the central index for defining the preclinical stage of SAD.

The CDC2 I-G-T haplotype associated with the APOE ɛ4 allele increases the risk of sporadic Alzheimer's disease in Sicily

2007 ◽  
Vol 419 (3) ◽  
pp. 195-198 ◽  
Author(s):  
Paolo Bosco ◽  
Filippo Caraci ◽  
Agata Copani ◽  
Rosario S. Spada ◽  
Maria Angela Sortino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sporadic Alzheimer’S Disease ◽  
E4 Allele ◽  
T Haplotype

scholarly journals The Moderating Effect of the APOE ɛ4 Allele on the Relationship Between Hippocampal Volume and Cognitive Decline in Older Depressed Patients

2011 ◽  
Vol 19 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Natalie Sachs-Ericsson ◽  
Kathryn Sawyer ◽  
Elizabeth Corsentino ◽  
Nicole Collins ◽  
David C. Steffens
Keyword(s):  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Moderating Effect ◽  
Depressed Patients ◽  
E4 Allele ◽  
The Relationship

scholarly journals Hippocampal Complex Atrophy in Poststroke and Mild Cognitive Impairment

2015 ◽  
Vol 35 (11) ◽  
pp. 1729-1737 ◽  
Author(s):  
Per Selnes ◽  
Ramune Grambaite ◽  
Mariano Rincon ◽  
Atle Bjørnerud ◽  
Leif Gjerstad ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Stage ◽  
Amyloid Β ◽  
Hippocampal Volume ◽  
White Matter Hyperintensity ◽  
Csf Biomarkers ◽  
Delayed Recall ◽  
Pathologic Processes ◽  
Hippocampal Complex

To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.

Apolipoprotein ɛ4 Affects Multiple Domains of Neuropsychological Functioning in a Sample of Elderly Hispanics

2020 ◽  
pp. 1-7
Author(s):  
Diana C. Oviedo ◽  
Ambar R. Perez-Lao ◽  
Julio A. Flores-Cuadra ◽  
Alcibiades E. Villarreal ◽  
Maria B. Carreira ◽  
...  
Keyword(s):  
Verbal Memory ◽  
Genetic Risk ◽  
Neuropsychological Functioning ◽  
Sporadic Alzheimer’S Disease ◽  
Cognitive Domains ◽  
Apolipoprotein E4 ◽  
Visuospatial Abilities ◽  
Global Cognition ◽  
E4 Allele ◽  
Multiple Domains

Apolipoprotein ɛ4 allele (APOE ɛ4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), but inconsistencies have arisen in studies with Hispanics. The objective of this study was to explore APOE ɛ4 expression and cognitive function in a sample of Panamanian older adults, including healthy controls, mild cognitive impairment, and AD. Participants with at least one copy of APOE ɛ4 had a significantly lower performance in global cognition, verbal memory, executive functions, visuospatial abilities, regardless of diagnosis. The present study contributes to the understanding of the association of APOE ɛ4 and impairment in specific cognitive domains in elderly Hispanics.

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