Problems meeting basic needs moderate the association between the APOE ϵ4 allele and cognitive decline

Objectives: The ApolipoproteinE ε4 (APOE ε4) allele influences cognitive decline (CD) in some but not in all individuals. The purpose of this study was to investigate whether problems meeting basic needs (BN) (e.g., having enough money to meet needs, having enough money for emergencies, having adequate housing, and having enough heat) influences the relationship between the APOE ε4 allele and CD. We predicted that problems meeting BN would have a greater influence on CD among those with the APOE ε4 allele than those without the allele.

Methods: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Data were drawn from Waves 1 and 2, which were 3 years apart. Cognitive functioning was assessed at both waves so that change in cognitive status was examined over time, and cognitive status was controlled at baseline. Genotyping, however, was not obtained until Wave 3.

Results: The APOE ε4 allele and problems meeting BN independently predicted CD. Importantly, the influence of BN on CD was greater for individuals with the APOE ε4 allele compared to those without the allele. Other indicators of socioeconomic status (e.g., education, income) did not interact with the APOE ε4 allele in predicting CD.

Conclusions: There is a synergistic effect of perceived problems meeting BN and the APOE ε4 allele on jointly influencing cognitive functioning. Although genetic risk factors are not easily modifiable, resource deprivation may be more amenable to interventions, which may reduce risk for CD.     

The apolipoprotein E ϵ4 allele and incident Alzheimer’s disease in persons with mild cognitive impairment

Possession of one or more copies of the apolipoprotein E (APOE) ?4 allele is a known risk factor for Alzheimer’s disease (AD), but it is uncertain whether the ?4 allele is associated with disease incidence among persons with mild cognitive impairment (MCI). We addressed this issue with data from the Religious Orders Study. Participants were 181 older Catholic clergy members who met criteria for MCI based on a uniform structured clinical evaluation; 56 (30.9%) had at least one ?4 allele. Clinical evaluations, which included clinical classification of dementia and AD, were repeated annually. During a mean of 5.7 years of observation, 79 persons (43.6%) developed AD. In a proportional hazards model that controlled for age, sex, and education, possession of an ?4 allele was associated with a 93% increase in the risk of developing Alzheimer’s disease (95% CI: 1.02, 2.63). There was a marginally significant reduction in the effect of ?4 in older compared to younger participants (p = .053). The results suggest that possession of an ?4 allele does increase risk of AD in persons with MCI.     

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

BackgroundSubjective cognitive concerns may represent a simple method to assess likelihood of memory decline among apolipoprotein E (APOE) ε4 carriers.MethodsWe examined the relationship of self-reported subjective cognitive concerns, using seven specific cognitive concerns, with memory and memory decline over 6 years among APOE ε4 carriers and non-carriers from the Nurses' Health Study.ResultsIn both groups, increasing subjective cognitive concern score predicted worse baseline memory and faster rates of subsequent memory decline, after adjustment for age, education and depression. The relation with baseline memory appeared statistically stronger in APOE ε4 carriers (P-interaction = 0.03). For memory decline, mean differences in slopes of episodic memory (95% CI) for 4 to 7 versus no concern = −0.05 (−0.10, 0.01) standard units in APOE ε4 carriers, and −0.04 (−0.08, −0.01) standard units in non-carriers.ConclusionsAPOE ε4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline.     

Amyloid-β₄₂ is associated with cognitive impairment in healthy elderly and subjective cognitive impairment

The aim of this study was to predict cognitive performance on the basis of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau) and amyloid-β?? (Aβ??) in controls and patients at various impairment levels. Previous studies have found an association of CSF T-tau levels with cognitive symptoms, but it has been difficult to relate Aβ to cognition, and it has thus been hypothesized that Aβ reaches a plateau level prior to cognitive symptoms. A comprehensive battery of neuropsychological tests was subjected to factor analysis to yield aggregated cognitive domains. Linear regression models were performed for the total sample of the Gothenburg MCI study (n = 435) and for each level of impairment. Aβ?? and T-tau accounted for a significant proportion of performance in all cognitive domains in the total sample. In controls (n = 60) and patients with subjective cognitive impairment (n = 105), Aβ?? predicted a significant proportion of semantic and working memory performance. For patients with mild cognitive impairment (n = 170), T-tau had the most pronounced impact across cognitive domains, and more specifically on episodic memory, visuospatial, and speed/executive performance. For patients with dementia (n = 100), the most pronounced impacts of Aβ?? were found in episodic memory and visuospatial functioning, while T-tau was substantially associated with episodic memory. Our results suggest that cognition is related to CSF biomarkers regardless of impairment level. Aβ?? is associated with cognitive functions from a potentially early to a later disease phase, and T-tau is more indicative of performance in a later disease phase.     

Association of apolipoprotein E ε4 allele with cognitive impairment in patients with epilepsy and interaction with phenytoin monotherapy

Cognitive impairment implicates many factors beyond phenytoin monotherapy in patients with epilepsy. Apolipoprotein E ε4 allele has been reported to play a role in severe memory impairment that ultimately progresses to Alzheimer's disease (AD); however, knowledge about its role in cognitive impairment in patients with epilepsy is lacking. Our study proposes the possible involvement of the APOE ε4 allele in cognitive impairment in patients with epilepsy which is further worsened by phenytoin monotherapy. Assessment of the APOE ε4 allele in a population with epilepsy will help to identify the patients vulnerable to cognitive impairment and, therefore, the corrective therapy that needs to be addressed.     

APOE ϵ4, rated life experiences,and affect among centenarians

Objectives: The purpose of this study was to assess the relationship between apolipoprotein E (APOE), life events and engagement, and subjective well-being (as measured by positive and negative affect) among centenarians. Based on the life stress paradigm, we predicted that higher levels of stress would allow APOE to influence positive and negative affect.

Method: 196 centenarians and near-centenarians (98 years and older) of the Georgia Centenarian Study participated in this research. The APOE, positive and negative affect, the number of recent (last 2 years) and lifelong (more than 20 years prior to testing) events, as well as a number of life engagement tasks were assessed.

Results: Results suggested that centenarians carrying the APOE ?4 allele rated lower in positive affect, the number of lifelong events, and in engaged lifestyle, when compared to centenarians without the APOE ?4 allele (t = 3.43, p < .01; t = 3.19, p < .01; and t = 2.33, p < .05, respectively). Blockwise multiple regressions indicated that the APOE ?4 predicted positive but not negative affect after controlling for demographics. Gene–environment interactions were obtained for the APOE ?4 and lifelong events, suggesting that carriers of the APOE ?4 allele had higher scores of negative affect after having experienced more events, whereas noncarriers had reduced negative affect levels after having experienced more events.

Conclusion: APOE ?4 is directly related to positive affect and is related to negative affect in interaction with life events.     

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer’s disease

Current evidence shows that apolipoprotein E(APOE), apolipoprotein CI(APOC1) and low density lipoprotein receptor-related protein(LRP) variations are related to late-onset Alzheimer's disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer's disease patients. We performed a 30-month longitudinal cohort study to investigate the relationship between Alzheimer's disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer's disease were recruited form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess patients' cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE ε4 carriers compared with non-carriers. In addition, the APOE ε4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive impairment progression group. In conclusion, APOE ε4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ε4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer's disease.     

Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment

Background

Basal forebrain cholinergic system (BFCS) dysfunction is associated with cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Apolipoprotein E (APOE) ε2 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on APOE.

Objective

We investigated the effect of the APOE ε2 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients.

Method

We included 60 MCI patients with APOE ε3/ε3, 18 MCI patients with APOE ε2/ε3, 73 CN subjects with APOE ε3/ε3, and 36 CN subjects with APOE ε2/ε3 genotypes who had resting-state functional magnetic resonance imaging data from the Alzheimer's disease Neuroimaging Initiative. We used BFCS subregions (Ch1-3 and Ch4) as seeds and calculated the FC with other brain areas. Using a mixed-effect analysis, we explored the interaction effects of APOE ε2 allele × cognitive status on BFCS-FC. Furthermore, we examined the relationships between imaging metrics, cognitive abilities, and AD pathology markers, controlling for sex, age, and education as covariates.

Results

An interaction effect on functional connectivity was found between the right Ch4 (RCh4) and left insula (p < 0.05, corrected), and between the RCh4 and left Rolandic operculum (p < 0.05, corrected). Among all subjects and APOE ε2 carriers, RCh4-left Insula FC was associated with early tau deposition. Furthermore, no correlation was found between imaging metrics and amyloid burden. Among all subjects and APOE ε2 carriers, FC metrics were associated with cognitive performance.

Conclusion

The APOE ε2 genotype may play a protective role during BFCS degeneration in MCI.     

Is quality of life associated with cognitive impairment in schizophrenia?

BACKGROUND: The subjectively assessed quality of life of schizophrenia patients is mostly lower than healthy subjects, and cognitive impairment is an integral feature of schizophrenia. The aims of the present study were to compare the quality of life and neurocognitive functioning between the patients with schizophrenia and the healthy subjects, and to examine the relationships between quality of life and neurocognitive functions among the patients with schizophrenia. METHODS: Thirty-eight patients with schizophrenia (15 women and 23 men) and 31 healthy individuals (18 women and 13 men) were included in the study. All participants were administered World Health Organization Quality of Life-Brief Form (WHOQOL-BREF) to assess their quality of life, and Digit Span Test (DST) and Controlled Oral Word Association Test (COWAT) for cognitive functions. RESULTS: The patients with schizophrenia demonstrated lower scores in physical (F=25.6, p=0.0001), psychological (F=15.85, p=0.0001) and social (F=37.7, p=0.0001) domains compared to control group. The patients with schizophrenia showed significantly lower scores on COWAT compared to healthy subjects (F=4.22, p=0.04). The social domain scores of WHOQOL correlated to DST total scores (r=0.45, p=0.007), DST forwards scores (r=0.54, p=0.001) and COWAT total scores (r=0.40, p=0.04) in patients with schizophrenia but not in the control group. The patients with lower level of cognitive functioning had lower scores on social domain of WHOQOL-BREF (z=-2.01, p=0.04). CONCLUSION: Our results confirm that the cognitive deficits in executive function and working memory appear to have direct impact on the patients' perceived quality of life especially in social domain which can either be a cause or a consequence of social isolation of patients with schizophrenia.     

β-Amyloid is associated with aberrant metabolic connectivity in subjects with mild cognitive impairment

Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer''s disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein E ɛ4 (APOE ɛ4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer''s Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ɛ4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ɛ4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns.     

Apolipoprotein E ε4 is not associated with cognitive impairment in patients with idiopathic REM sleep behavior disorder

We analyzed 136 patients (age, 67.5 ± 6.9 years; men, 59.6%) with idiopathic rapid eye movement sleep behavior disorder (iRBD). The results of the neuropsychological tests were not significantly different between APOE ε4 carriers and noncarriers, suggesting that the APOE ε4 allele was not associated with cognitive impairment in iRBD.     

Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE ε4 allele

Cholesterol regulates the production of amyloid beta (Aβ), which is central to the pathogenesis of Alzheimer's disease (AD), with high cellular cholesterol promoting and low cellular cholesterol reducing Aβ in vitro and in vivo. High density lipoprotein (HDL) plays a central role in the removal of excess cholesterol from cells, and cholesteryl ester transfer protein (CETP) is a crucial protein involved in the regulation of HDL levels. Two common polymorphisms in the promoter region (C–629A) and exon 14 I405V of the CETP gene are associated with CETP activity and HDL levels. To investigate if these sequence variants in CETP might be of importance in mediating susceptibility to AD, independently or in concert with apolipoprotein E (APOE) ε4 allele, we studied a sample of 286 Spanish AD patients and 315 healthy controls. In APOE ε4 carriers, homozygous for the CETP (–629) A allele had approximately a three times lower risk of developing AD (odds ratio 2.33, 95% CI 1.01–5.37), than homozygous and heterozygous carriers of the CETP (–629) C allele (odds ratio 7.12, 95% CI 4.51–11.24, P for APOE ε4/CETP (–629) AA genotype interaction < 0.001). Our data suggest that CETP behaves as a modifier gene of the AD risk associated with the APOE ε4 allele, possibly through modulation of brain cholesterol metabolism.     

The effect of MAPT H1 and APOE ε4 on transition from mild cognitive impairment to dementia

Microtubule-associated protein tau (MAPT) and apolipoprotein E (APOE) are involved in the pathogenic mechanisms of Alzheimer's disease (AD). We prospectively followed three longitudinal independent samples (total n=319) with amnestic mild cognitive impairment (MCI) and analyzed whether MAPT H1/H2 haplotypes and APOE ε4 polymorphisms accelerated the rate of progression from MCI to dementia. At the end of the study, 172 subjects remained cognitively stable, whereas 147 progressed to dementia. APOE ε4 and MAPT H1/H1 were independently associated with an increased rate of progression to dementia in the combined sample. Cox regression models of the combined MCI sample showed that MAPT H1/H1 carriers had an increased rate of progression to dementia compared with non carriers (Hazard Ratio =1.45; 95% CI=1.04-2.02; p=0.028) and time-to-progression was shortened by 1.37 years. APOE ε4 allele also accelerated progression to dementia (Hazard Ratio=1.47; 95% CI= 1.06-2.04; p=0.020) and reduced the time-to-progression by 0.87 years. Additionally, MAPT H1/H1 genotype and APOE ε4 allele had an additive effect in progression to dementia, increasing progression rate to dementia (Hazard Ratio=2.24, 95% CI =1.40-3.58; p=0.001) and shortening time-to-progression to dementia by 2.92 years. Similar results were obtained when only considering progression to AD-type dementia. Our results suggest that both MAPT H1/H1 genotype and APOE ε4 allele lead to a more rapid progression to dementia among MCI subjects, probably mediating an increased rate of amyloid-β and tau brain deposition.     

Blood pressure variability and medial temporal atrophy in apolipoprotein ϵ4 carriers

Brain Imaging and Behavior - Blood pressure variability is an emerging risk factor for dementia but relationships with markers of neurodegeneration and Alzheimer’s disease risk are...     

Translational perspective: is cinnamon a suitable agent for cognitive impairment and Alzheimer's disease associated with brain trauma?

<正>Cinnamon,is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases(Kawatra et al.,2015).Besides its anti-inflammatory,anti-diabetic and anti-cancer properties,cinnamon also exerts strong brain protective and pro-cognitive effects in various models of neurodegeneration(Kawatra et al.,2015;Kelestemur et al.,2016)(Figure 1).Traumatic brain injury(TBI)is