Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Trzepacz, Paula T.; Hochstetler, Helen; Yu, Peng; Castelluccio, Peter; Witte, Michael M.; Dell’Agnello, Grazia; Degenhardt, Elisabeth K.

doi:10.1159/000441351

Cited by 14 publications

(6 citation statements)

References 51 publications

(67 reference statements)

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“…Those with more than one of the three risk factors had a significantly higher risk of mild cognitive impairment and dementia than those with one or none of these risk factors [ 1 , 2 ]. We did not observe a significant association among WMLs, Aβ burden, and hippocampal volume in our study population, which was similar to results of previous studies [ 25 , 26 , 27 ]. However, cortical thickness was negatively associated with Aβ burden and WMLs.…”

Section: Discussionsupporting

confidence: 92%

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans

et al. 2021

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The Alzheimer’s Disease Neuroimaging Initiative showed that Japanese had significantly lower brain Aβ burden than Americans among a cognitively normal population. This cross-sectional study aimed to compare vascular disease burden, Aβ burden, and neurodegeneration between cognitively normal elderly Japanese and Americans. Japanese and American participants were matched for age (± 4-year-old), sex, and Apolipoprotein E (APOE) genotype. Brain vascular disease burden and brain Aβ burden were measured using white matter lesions (WMLs) and 11C-labeled Pittsburgh Compound B (PiB) retention, respectively. Neurodegeneration was measured using hippocampal volumes and cortical thickness. A total of 95 Japanese and 95 Americans were recruited (50.5% men, mean age = 82). Compared to Americans, Japanese participants had larger WMLs, and a similar global Aβ standardized uptake value ratio (SUVR), cortical thickness and hippocampal volumes. Japanese had significantly lower regional Aβ SUVR in the anterior ventral striatum, posterior cingulate cortex, and precuneus. Cognitively normal elderly Japanese and Americans had different profiles regarding vascular disease and Aβ burden. This suggests that multiple risk factors are likely to be involved in the development of dementia. Additionally, Japanese might have a lower risk of dementia due to lower Aβ burden than Americans. Longitudinal follow-up of these cohorts is warranted to ascertain the predictive accuracy of these findings.

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Section: Discussionsupporting

confidence: 92%

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans

et al. 2021

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“…β-Amyloid (Aβ) accumulation has been linked to brain atrophy [ 1 – 3 ] and cognitive decline in AD [ 1 – 7 ]. However, findings have been mixed regarding whether and how A + relates to cognitive dysfunction or hippocampal volume (HV) across the spectrum of normal cognition (NC), early mild cognitive impairment (eMCI), and AD [ 4 , 8 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume

et al. 2017

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BackgroundAlzheimer’s disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A+) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI).MethodsSeven hundred forty-two participants with NC and participants with eMCI from the Alzheimer’s Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included. All had baseline florbetapir PET measured, and 526 had screening visit HV measured. Regression moderation models were used to examine whether A+ effects on Rey Auditory Verbal Learning Test learning and delayed recall and right and left HV (adjusted for total intracranial volume) were moderated by diagnosis and sex. Age, cognition at screening, education, and apolipoprotein E ε4 carrier status were controlled.ResultsWomen with A+, but not those with florbetapir PET amyloid negative (A-),eMCI showed poorer learning. For women with NC, there was no relationship of A+ with learning. In contrast, A+ men trended toward poorer learning regardless of diagnosis. A similar trend was found for verbal delayed recall: Women with A+, but not A-, eMCI trended toward reduced delayed recall; no effects were observed for women with NC or for men. Hippocampal analyses indicated that women with A+, but not those with A−, eMCI, trended toward smaller right HV; no significant A+ effects were observed for women with NC. Men showed similar, though nonsignificant, patterns of smaller right HV in A+ eMCI, but not in men with A− eMCI or NC. No interactive effects of sex were noted for left HV.ConclusionsWomen with NC showed verbal learning and memory scores robust to A+, and women with A+ eMCI lost this advantage. In contrast, A+ impacted men’s scores less significantly or not at all, and comparably across those with NC and eMCI. Sex marginally moderated the relationship of A+ and diagnosis with right HV, such that women with NC showed no A+ effect and women with A+ eMCI lost that advantage in neural integrity; the pattern in men was less clear. These findings show that women with A+ eMCI (i.e., prodromal AD) have differential neural and cognitive decline, which has implications for considering sex in early detection of AD and development of therapeutics.

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“…Moreover, the between‐group median differences observed in left and right hippocampal volumes (−11.3 and − 7.3%, respectively) may further strengthen the CR hypothesis by highlighting the advanced underlying pathological state in the HF group, considering the 3–5% annual hippocampal atrophy rates previously reported in aMCI (Jack Jr. et al, 2000; Joko et al, 2016). In addition, although not assessed in the current study, the level of hippocampal atrophy has been linked to the burden of other hallmark features of AD pathology in MCI including amyloid‐beta deposition (Hanseeuw, Schultz, Betensky, Sperling, & Johnson, 2016; Huijbers et al, 2015; Ottoy et al, 2019; Trzepacz et al, 2016). The similar associative memory performance observed between the groups would have been unexpected if not in the context of CR, as a type of memory highly sensitive to the neurocognitive decline observed in aMCI (Troyer et al, 2008), and to hippocampal structural deterioration in these patients (Nathan et al, 2017; Villeneuve & Belleville, 2012).…”

Section: Discussionmentioning

confidence: 88%

Maximal aerobic capacity is associated with hippocampal cognitive reserve in older adults with amnestic mild cognitive impairment

et al. 2020

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Maximal aerobic capacity (MAC) has been associated with preserved neural tissue or brain maintenance (BM) in healthy older adults, including the hippocampus. Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease. While aMCI is characterized by hippocampal deterioration, the MAC‐hippocampal relationship in these patients is not well understood. In contrast to healthy individuals, neurocognitive protective effects in neurodegenerative populations have been associated with mechanisms of cognitive reserve (CR) altering the neuropathology‐cognition relationship. We investigated the MAC‐hippocampal relationship in aMCI (n = 29) from the perspectives of BM and CR mechanistic models with structural MRI and a memory fMRI paradigm using both group‐level (higher‐fit patients vs. lower‐fit patients) and individual level (continuous correlation) approaches. While MAC was associated with smaller hippocampal volume, contradicting the BM model, higher‐fit patients demonstrated statistically significant lower correlation between hippocampal volume and memory performance compared with the lower‐fit patients, supporting the model of CR. In addition, while there was no difference in brain activity between the groups during low cognitive demand (encoding of familiar stimuli), higher MAC level was associated with increased cortical and sub‐cortical activation during increased cognitive demand (encoding of novel stimuli) and also with bilateral hippocampal activity even when controlling for hippocampal volume, suggesting for an independent effect of MAC. Our results suggest that MAC may be associated with hippocampal‐related cognitive reserve in aMCI through altering the relationship between hippocampal‐related structural deterioration and cognitive function. In addition, MAC was found to be associated with increased capacity to recruit neural resources during increased cognitive demands.

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Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

Cited by 14 publications

References 51 publications

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans

Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume

Maximal aerobic capacity is associated with hippocampal cognitive reserve in older adults with amnestic mild cognitive impairment

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