Depression, APOE genotype and subjective memory impairment: a cross-sectional study in an African-Caribbean population

Abstract

Background. Subjective memory impairment (SMI) is common in older populations but its aetiology and clinical significance is uncertain. Depression has been reported to be strongly associated with SMI. Associations with objective cognitive impairment are less clear cut. Other factors suggested to be associated with SMI include poor physical health and the apolipoprotein E (APOE) ε4 allele. Studies of SMI have been predominantly confined to white Caucasian populations.Method. A community study was carried out in a UK African-Caribbean population aged 55–75, sampled from primary care lists. Twenty-three per cent were classified with SMI. Depression was defined using the 10-item Geriatric Depression Scale. Other aetiological factors investigated were education, objective cognitive function, APOE genotype, disablement and vascular disease/risk. The principal analysis was restricted to 243 participants scoring > 20 on the Mini-Mental State Examination (85%). A second analysis included all 290 participants.Results. Depression, self-reported physical impairment and APOE ε4 were associated with SMI. The association between SMI and physical impairment was not explained by depression, vascular disease/risk, or disability/handicap. The association between ε4 and SMI increased as MMSE scores decreased and was particularly strong in those with depression. The ε4 allele was present in 69% (95% CI 41–89%) of those with depression and SMI compared with 28% (20–36%) of those with neither.Conclusions. Depression may not be a sufficient explanation for subjective memory complaints. Memory complaints in the presence of depression are associated with high prevalence of ε4 and therefore, presumably, a raised risk of subsequent dementia.

Subjective Cognition and Amyloid Deposition Imaging

“…The significant relationship observed between PiB uptake and subjective cognition measured with general memory self-reports relative to age-equivalent peers echoes previous studies showing that memory complaints in healthy people were related to genetic risks[25]and brain structural and functional features of AD[18,22]. In reference to the biomarker cascade model of AD proposed by Jack et al[11]Aβ deposition measure in cognitively intact older subjects may be the most appropriate measure to detect the earliest manifestation of AD.…”

“…Although the present study did not specifically recruit SCI subjects, previous work in SCI has shown brain structural and functional abnormalities that mimic those commonly observed in AD (i.e. decreased grey matter volume[16–21], cerebral metabolism reduction[22,23]), as well as increased genetic risk for AD (such as apolipoprotein E ε4 allele[24,25]). Furthermore, postmortem studies have consistently observed that memory complaints in healthy older adults were associated with amyloid in autopsied tissues at death[26,27].…”

Resolving the relationship between ApolipoproteinE and depression

“…Among those with LOAD, the estimated APOE4 allele frequency is 0.423 (versus 0.128 among the cognitive controls) and is strongly associated with LOAD (p<0.001) as has been replicated many times in previous studies (Table 3). To be consistent with other studies [5,6,9,17,21,23,27,30,35] we also tested genotypes based on presence or absence of the APOE4 allele and found strong association between carriers and LOAD (OR=6.5; p<0.001; Table 3). …”

“…However, in addition to LOAD, APOE4 has been implicated as a risk factor for several neuropsychiatric disorders including LOD. At least nine studies have reported an association between APOE4 and depressive phenomenology (Table 1) [4,6,9,16,25,27,29,30,35]. While there are positive studies demonstrating association between APOE4 and depression in the elderly, there are also negative reports [7,8, 11,12,17,18,20–23,37,39].…”

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

“…SCC have been found to predict accelerated memory decline [6], increased risk of AD [7–9], and have been associated with the presence of neurobiological markers of AD (eg, grey matter atrophy [10–14], white matter integrity [15], amyloid burden [16, 17] and AD pathology at autopsy [18]). Although APOE ε4 has been associated with a greater prevalence of SCC [19–21], very limited research has addressed whether SCC predict memory decline in APOE ε4 carriers [22]. …”