Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct;72(4):571-7.
doi: 10.1002/ana.23643.

Alzheimer disease family history impacts resting state functional connectivity

Liang Wang  1 , Catherine M Roe, Abraham Z Snyder, Matthew R Brier, Jewell B Thomas, Chengjie Xiong, Tammie L Benzinger, John C Morris, Beau M Ances
Affiliations

Alzheimer disease family history impacts resting state functional connectivity

Liang Wang et al. Ann Neurol. 2012 Oct.

Abstract

Objective: Offspring whose parents have Alzheimer disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele noncarriers.

Methods: We studied a cohort of 348 cognitively normal participants with or without family history of late onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging.

Results: A family history of late onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele noncarriers.

Interpretation: Unknown genetic factors, embodied in a family history of late onset AD, may affect DMN integrity prior to cognitive impairment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Localization of regions of interest for subsequent analysis of cognitively normal participants. Using a seed (red sphere) placed in the posterior cingulate cortex (PCC), functional connectivity maps were constructed for eight mild Alzheimer’s disease (AD) participants with a family history of late-onset AD and eight cognitively normal participants without a family history of late-onset AD. A group difference map was produced by subtracting the averaged map of mild AD patients from that of cognitively normal individuals. Regions (yellow) comprising of at least 10 voxels that exhibited significant differences (exceeding a threshold of z(r) =0.25) between the two groups (cognitively normal minus AD) are overlaid on axial anatomic images. The MNI coordinates of peak loci for these regions are listed in Supplementary Table S1. Left in the images refers to anatomical orientation.
Figure 2
Figure 2
The effect of a family history of late-onset AD on resting state functional connectivity in cognitively normal individuals Bar graphs (A-C) display covariates-adjusted means (y axis) of correlation coefficients for participants without a family history (FH-) and with (FH+) a family history of late-onset AD. Data are presented for the entire sample (A), apolipoprotein E ε4 (APOE ε4) non-carriers (B), and APOE ε4 carriers (C) respectively. *: p < 0.05, adjusting for age, sex and the presence of APOE ε4 allele in (A), and adjusting for age and sex in (B) and (C). Error bars in A-C represent one standard error of the mean. Statistical analyses for the data in A are presented in Supplementary Table S2. Correlation coefficients between the PCC and RSC (y axis) are plotted against age (x axis) and family history of AD in (D). An age-related decrease in functional connectivity is present in individuals with a family history of AD (FH+) (Pearson r = -0.25, p < 0.001) but not in those without a family history of AD (FH-) (Pearson r = 0.07, p = 0.41). PCC: posterior cingulate cortex, LIPL: left inferior parietal lobule, RIPL: right inferior parietal lobule; MPFC: medial prefrontal cortex; LMTL: left medial temporal lobe; RMTL: right medial temporal lobe, RSC: retrosplenial cortex.
Figure 3
Figure 3
MTL volumetric measures for cognitively normal individuals with and without a family history of late-onset AD Bar graphs show covariates-adjusted means (y axis) of the entorhinal cortical thickness (A) and standardized hippocampal volume (B). Both p ≥ 0.56 after adjusting for age, sex, and the presence of APOE ε4 allele. ERC: entorhinal cortex, HF: hippocampal formation.
See this image and copyright information in PMC

References

    1. Thies W, Bleiler L. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement. 2011;7(2):208–44. - PubMed
    1. Gatz M, Reynolds CA, Fratiglioni L, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006 Feb;63(2):168–74. - PubMed
    1. Tanzi RE, Bertram L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell. 2005 Feb 25;120(4):545–55. - PubMed
    1. Campion D, Dumanchin C, Hannequin D, et al. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999 Sep;65(3):664–70. - PMC - PubMed
    1. Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology. 1993 Aug;43(8):1467–72. - PubMed

Publication types

MeSH terms