While APOE ε4 allele is considered a genetic risk factor for Alzheimer's disease (AD), no relation existed between APOE ε4 and AD in the Yoruba in Nigeria among cohorts included in early prevalence waves. The authors’ explanation that other disease susceptibilities may provoke earlier mortality is inconsistent with the Yoruba having a lower incidence of disease risk factors. Cohort enrichment in 2001 has altered the authors’ conclusions; Yorba participants homozygous, and not heterozygous, for the ε4 allele had significantly increased risk for AD (HR = 2.95, p = 0.0002) (Hendrie et al., 2014). This is a critical revelation, yet it is not clear why such a temporal relationship exists between risk genotypes and AD among the Yoruba. This letter proposes an explanation.

Cortisol dysregulation has been reported in dementia and depression. Cortisol levels and its associates were investigated among older people living at home and in nursing homes, in a cross-sectional study. A sample of 650 older people, from the community (home and nursing homes) and specialized care (memory clinics and old age psychiatry wards), mean age 76.8 (SD = 10.3) (dementia n = 319, depression, n = 154, dementia plus depression n = 53, and reference group n = 124), was included. Assessment included the Mini Mental State Examination (MMSE), Cornell scale for depression in dementia, activities of daily living scales, and salivary cortisol. Number of drugs was registered. The results showed that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. Characteristics significantly associated with cortisol levels were higher MMSE score (in patients with dementia and co-morbid depression), male gender (in people with dementia), and number of medications (in the reference group). We conclude that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. The association of cortisol level with MMSE score among patients with dementia and depression could further indicate that increased stress is related to cognitive function.

Liu et al. (2017) investigated caregiver burden of patients with frontotemporal lobar degeneration (FTD) and dementia with Lewy bodies (DLB), which was compared with caregivers of patients with Alzheimer's disease. The authors concluded that the frequency and severity of behavioral disturbances in caregiver of patients with FTD and DLB were higher than those with caregivers of patients with Alzheimer's disease. I have some concerns about their study.

Little is known about olfactory identification (OI) function in early-onset Alzheimer’s disease (EOAD) and early-onset mild cognitive impairment (eoMCI) with age of onset <65 years. We aimed to study OI in EOAD compared with eoMCI and age-matched healthy controls (HC). Nineteen EOAD subjects with mild to moderate dementia, 17 with eoMCI, and 21 HC recruited as a convenience sample from memory services were assessed for cognition, behavioral symptoms, and activities for daily living. The OI was tested using the University of Pennsylvania smell identification test (UPSIT). EOAD participants performed worse compared with eoMCI and HC on cognitive tests and OI (p < 0.001). Although eoMCI had poorer cognitive scores compared to HC, they were similar in their OI function. OI correlated with attention (r = 0.494, p = 0.031), executive functions (r = 0.508, p = 0.026), and praxis (r = 0.455, p = 0.05) within the EOAD group. OI impairment was significantly associated with the diagnosis of EOAD versus eoMCI, but not with eoMCI when compared with HC. OI could potentially be useful in differentiating EOAD from eoMCI. Studies with late-life MCI patients showing OI impairment relative to HC may be attributed to a different disease process. Independent replication in a larger sample is needed to validate these findings.