Dataset Information

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status.

ABSTRACT: The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer's Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis^∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied.

SUBMITTER: Hestad K

PROVIDER: S-EPMC8236580 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Alzheimer's disease (AD) is the most common form of dementia and the leading risk factor, after age, is possession of the apolipoprotein E epsilon 4 allele (APOE4). Approximately 50% of AD patients carry one or two copies of APOE4 but the mechanisms by which it confers risk are still unknown. APOE4 carriers are reported to demonstrate changes in brain structure, cognition, and neuropathology, but findings have been inconsistent across studies. In the present study, we used multi-modal data to characterise the effects of APOE4 on the brain, to investigate whether AD pathology manifests differently in APOE4 carriers, and to determine if AD pathomechanisms are different between carriers and non-carriers. Brain structural differences in APOE4 carriers were characterised by applying machine learning to over 2000 brain MRI measurements from 33,384 non-demented UK biobank study participants. APOE4 carriers showed brain changes consistent with vascular dysfunction, such as reduced white matter integrity in posterior brain regions. The relationship between APOE4 and AD pathology was explored among the 1260 individuals from the Religious Orders Study and Memory and Aging Project (ROSMAP). APOE4 status had a greater effect on amyloid than tau load, particularly amyloid in the posterior cortical regions. APOE status was also highly correlated with cerebral amyloid angiopathy (CAA). Bulk tissue brain transcriptomic data from ROSMAP and a similar dataset from the Mount Sinai Brain Bank showed that differentially expressed genes between the dementia and non-dementia groups were enriched for vascular-related processes (e.g., "angiogenesis") in APOE4 carriers only. Immune-related transcripts were more strongly correlated with AD pathology in APOE4 carriers with some transcripts such as TREM2 and positively correlated with pathology severity in APOE4 carriers, but negatively in non-carriers. Overall, cumulative evidence from the largest neuroimaging, pathology, and transcriptomic studies available suggests that vascular dysfunction is key to the development of AD in APOE4 carriers. However, further studies are required to tease out non-APOE4-specific mechanisms.

Dataset Information

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets