Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume

173

128

Background This study assessed APOE ε4 carrier status effects on Alzheimer’s disease (AD) imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC). Methods Cognitively normal, SMC, and early mild cognitive impairment participants from ADNI were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [18F]Florbetapir amyloid positivity on CSF biomarkers. Results SMC ε4+ showed greater amyloid deposition than SMC ε4−, but no hypometabolism or MTL atrophy. SMC ε4+ showed lower Aβ1–42 and higher tau/p-tau than ε4−, which were most abnormal in APOE ε4+ and cerebral amyloid positive SMC. Conclusion SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

Risacher

Kim

Nho

et al. 2015

173

128

“…In a small cross-sectional study, APOE ε4 carriers with SCC referred to a memory clinic had lower hippocampal volumes than those without memory impairment [39]. APOE ε4 carriers with SCC (defined by a single question, ie, reporting occasional forgetting names or forgetting where one placed objects) had greater brain hypometabolism (a marker of loss of synaptic function due to neuronal damage) in the same regions as those affected in AD patients, and increased levels of AD biomarkers in the cerebrospinal fluid, as compared to carriers without subjective memory concerns [40].…”

Section: Discussionmentioning

confidence: 99%

Subjective cognitive concerns, episodic memory, and the APOE ε4 allele

Samieri

Proust‐Lima

Glymour

et al. 2014

Background Subjective cognitive concerns may represent a simple method to assess likelihood of memory decline among APOE ε4 carriers. Methods We examined the relationship of self-reported subjective cognitive concerns, using 7 specific cognitive concerns, with memory and memory decline over 6 years among APOE ε4 carriers and non-carriers from the Nurses’ Health Study. Results In both groups, increasing subjective cognitive concern score predicted worse baseline memory and faster rates of subsequent memory decline, after adjustment for age, education and depression. The relation with baseline memory appeared statistically stronger in APOE ε4 carriers (P-interaction=0.03). For memory decline, mean differences in slopes of episodic memory (95% CI) for 4 to 7 versus no concern = −0.05 (−0.10, 0.01) standard units in APOE ε4 carriers, and −0.04 (−0.08, −0.01) standard units in non-carriers. Conclusions APOE ε4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline.

“…There is evidence from some memory clinic and population-based studies of an overrepresentation of the APOE ε4 allele in SCD, a particular association of APOE ε4 and biomarker evidence for AD in SCD, and an effect of APOE ε4 on the prospective risk of cognitive decline in SCD [58–61]. To further elucidate the potential use of the APOE genotype in predicting preclinical AD and cognitive decline in SCD, it should be reported in SCD studies, if available.…”

Section: Apolipoprotein E Genotypementioning

confidence: 99%

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

Jessen

Amariglio

Boxtel

et al. 2014

2,236

2,462

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer’s disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.