A meta-analysis of hippocampal atrophy rates in Alzheimer's disease

Barnes, Josephine; Bartlett, Jonathan; Pol, Laura A. van de; Loy, Clement T.; Scahill, Rachael I.; Frost, Chris; Thompson, Paul M.; Fox, Nick C.

doi:10.1016/j.neurobiolaging.2008.01.010

Cited by 319 publications

(235 citation statements)

References 34 publications

(47 reference statements)

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“…Limitations of this study include the relatively short follow-up time interval of two years between Waves of data collection, however the hippocampal atrophy observed was comparable to previous reports in normal aging (e.g., Barnes et al, 2009). As our studies continue to collect data, it will facilitate a more detailed examination of the influence of genetic variation in KIBRA and CLSTN2 on longitudinal memory performance and change in hippocampal volume.…”

Section: Discussionsupporting

confidence: 50%

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure.However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.

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Section: Discussionsupporting

confidence: 50%

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

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“…The hippocampal atrophy rates among our cohort, however, are similar to that of a recent meta-analysis which estimated a rate of Ϫ1.41%/year among normal controls. 30 Furthermore, an association between APOE2 and cerebral amyloid angiopathy, which can lead to lobar hemorrhages, has been described. 31 These would have been excluded from the ADNI with an abnormal screening MRI, thus removing a potential source for a detrimental effect of APOE2.…”

Section: Resultsmentioning

confidence: 99%

Hippocampal atrophy rates and CSF biomarkers in elderly APOE 2 normal subjects

Chiang

Insel²,

Tosun

et al. 2010

Neurology

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Objective: To determine whether elderly normal APOE E2 (APOE2) carriers exhibit slower rates of hippocampal atrophy and memory decline compared to APOE3/3 carriers. We also determined whether APOE2 carriers have less Alzheimer pathology as reflected by CSF biomarkers. Methods:We included longitudinal data from 134 cognitively normal individuals (27 APOE2/2 or E2/3, 107 APOE3/3) from the Alzheimer's Disease Neuroimaging Initiative, a prospective cohort study. A linear mixed-effects model was used to determine how APOE2 affected rates of hippocampal atrophy and cognitive change over time. In a subsample of 72 individuals who also underwent CSF analysis, an ordinary least-squares regression was used to determine whether CSF ␤-amyloid (A␤), total tau, and phosphorylated tau-181 (p-tau) differed by APOE2 status.Results: APOE2 carriers demonstrated slower rates of hippocampal atrophy (p ϭ 0.004). The mean rate of hippocampal atrophy among APOE2 carriers was Ϫ33 mm 3 /year (95% confidence interval Ϫ65 to ϩ0.4), or Ϫ0.5%/year, compared to Ϫ86 mm 3 /year (95% confidence interval Ϫ102 to Ϫ71), or Ϫ1.3%/year, in the APOE3/3 group. No differences in the rates of episodic memory (p ϭ 0.23) or overall cognitive change (p ϭ 0.90) were detected. In the CSF subsample, APOE2 carriers had higher levels of CSF A␤ (p ϭ 0.01), lower p-tau (p ϭ 0.02), and marginally lower tau (p ϭ 0.12). Conclusion:A slower rate of hippocampal atrophy in normal APOE2 carriers is consistent with the lower risk of Alzheimer disease in these individuals. We hypothesize that the slower atrophy rate is related to decreased preclinical Alzheimer pathology. Neurology The association between APOE genetic polymorphisms and differing risks of developing Alzheimer disease (AD) has been well-described, 1,2 although the mechanism remains unclear. Approximately 70% of the population carry the common APOE3/3 genotype, 25% carry at least one APOE4 allele, and 5% carry an APOE2 allele.3 Even before clinical evidence of memory impairment, APOE4 carriers demonstrate more rapid rates of memory decline.4-7 On the other hand, carrying an APOE2 allele is associated with slower rates of memory decline 8 and is considered protective against the development of AD.

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“…Barnes et al showed that the overall hippocampal atrophy rate is 1.4% in healthy patients from 69 to 83 years; this rate increased to 4.6% for subjects with Alzheimer's disease [34]. Rivastigmine is a selective cholinesterase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

et al. 2010

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Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer's disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.

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A meta-analysis of hippocampal atrophy rates in Alzheimer's disease

Cited by 319 publications

References 34 publications

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

Hippocampal atrophy rates and CSF biomarkers in elderly APOE 2 normal subjects

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

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