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APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression.
Int J Geriatr Psychiatry 2003; 18(12):1075-81IJ

Abstract

OBJECTIVE

There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD.

METHODS

We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n=160), AD (n=568) and elderly control (EC; n=156) subjects.

RESULTS

The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/-20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group.

CONCLUSIONS

The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated.

Authors+Show Affiliations

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. buttersma@upmc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14677138

Citation

Butters, Meryl A., et al. "APOE Is Associated With Age-of-onset, but Not Cognitive Functioning, in Late-life Depression." International Journal of Geriatric Psychiatry, vol. 18, no. 12, 2003, pp. 1075-81.
Butters MA, Sweet RA, Mulsant BH, et al. APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression. Int J Geriatr Psychiatry. 2003;18(12):1075-81.
Butters, M. A., Sweet, R. A., Mulsant, B. H., Ilyas Kamboh, M., Pollock, B. G., Begley, A. E., ... DeKosky, S. T. (2003). APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression. International Journal of Geriatric Psychiatry, 18(12), pp. 1075-81.
Butters MA, et al. APOE Is Associated With Age-of-onset, but Not Cognitive Functioning, in Late-life Depression. Int J Geriatr Psychiatry. 2003;18(12):1075-81. PubMed PMID: 14677138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression. AU - Butters,Meryl A, AU - Sweet,Robert A, AU - Mulsant,Benoit H, AU - Ilyas Kamboh,M, AU - Pollock,Bruce G, AU - Begley,Amy E, AU - Reynolds,Charles F,3rd AU - DeKosky,Steven T, PY - 2003/12/17/pubmed PY - 2004/2/12/medline PY - 2003/12/17/entrez SP - 1075 EP - 81 JF - International journal of geriatric psychiatry JO - Int J Geriatr Psychiatry VL - 18 IS - 12 N2 - OBJECTIVE: There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD. METHODS: We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n=160), AD (n=568) and elderly control (EC; n=156) subjects. RESULTS: The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/-20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group. CONCLUSIONS: The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated. SN - 0885-6230 UR - https://www.unboundmedicine.com/medline/citation/14677138/APOE_is_associated_with_age_of_onset_but_not_cognitive_functioning_in_late_life_depression_ L2 - https://doi.org/10.1002/gps.1006 DB - PRIME DP - Unbound Medicine ER -