Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence

Hersi, Mona; Irvine, Brittany; Gupta, Pallavi; Gomes, James; Birkett, Nicholas; Krewski, Daniel

doi:10.1016/j.neuro.2017.03.006

Cited by 263 publications

(206 citation statements)

References 249 publications

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“…Moreover, using verbal episodic memory tasks, previous studies have shown greater activation of areas affected in AD (e.g., dorsolateral prefrontal cortex and superior temporal gyrus) during episodic retrieval in young adults with at higher genetic risk of AD (Braskie et al, 2013). However, although APOE4 is the strongest genetic risk factor for late-onset AD (Hersi et al, 2017), presence of the allele does not appear to be a significant independent predictor of AD O'Donoghue et al, 2018).…”

Section: Few Group Differences In Task Activation Patternsmentioning

confidence: 84%

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

Rabipour

Rajagopal

et al. 2019

Preprint

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Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent's conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory.Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network.However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.

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Section: Few Group Differences In Task Activation Patternsmentioning

confidence: 84%

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

Rabipour

Rajagopal

et al. 2019

Preprint

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“…In the past decades, researchers have tried to establish sAD models in a variety of animals including rabbits, dogs, rodent rats, mice, and nonhuman primates (NHPs) …”

Section: Introductionmentioning

confidence: 99%

“…In the past decades, researchers have tried to establish sAD models in a variety of animals including rabbits, dogs, rodent rats, mice, and nonhuman primates (NHPs). [39][40][41][42][43] Unfortunately, currently available models only mimic partial changes of sAD in pathology, biochemistry, and/or cognitive ability. In this study, we reviewed the establishment, pathological features, and the underlying mechanisms of these sAD animal models.…”

mentioning

confidence: 99%

Advance of sporadic Alzheimer's disease animal models

Zhang

Chen

Mak

et al. 2019

Medicinal Research Reviews

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Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti‐AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti‐AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti‐AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti‐AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti‐AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.

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“…The protein APOE is involved in cholesterol metabolism and lipid homeostasis in the brain 23 . APOE has three alleles e2, e3 and e4 and carriage of APOE-e4 is the largest known genetic risk factor of LOAD with e4 homozygotes having a 14-fold increase in their lifetime risk of developing LOAD compared with APOE-e2 and e3 carriers 24,25 . APOE is the main cholesterol transporter in the brain 16 and the APOE-e4 isoform is thought to have fewer molecules to deliver cholesterol required for myelin and synaptic repair 16,26 .…”

Section: Introductionmentioning

confidence: 99%

“…APOE is the main cholesterol transporter in the brain 16 and the APOE-e4 isoform is thought to have fewer molecules to deliver cholesterol required for myelin and synaptic repair 16,26 . It is wellestablished that APOE-e4 is associated with an earlier onset of LOAD 24,27 and a larger burden of amyloid-β plaques [28][29][30][31][32] . This is particularly the case in those individuals with a FH of LOAD 33,34 .…”

Section: Introductionmentioning

confidence: 99%

Genetic risk of dementia modifies the impact of obesity on limbic white matter and spatial navigation behavior in cognitively healthy adults

Mole

Fasano

Evans

et al. 2019

Preprint

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A family history (FH) of dementia, APOE-e4 genotype, and obesity are major risk factors for developing Alzheimer's disease but their combined effects on the brain and cognition remain elusive. We tested the hypothesis that these risk factors affect apparent white matter (WM) myelin and cognition including spatial navigation and processing speed in 166 asymptomatic individuals (38-71 years). Microstructure in temporal [fornix, parahippocampal cingulum, uncinate fasciculus], motor and whole-brain WM was assessed with myelin-sensitive indices from quantitative magnetization transfer [macromolecular proton fraction (MPF)] and axon density from diffusion imaging. Individuals with the highest genetic risk compared to those with FH+ alone showed obesity-related reductions in MPF and axon density in the right parahippocampal cingulum. No effects were present for those without FH.Furthermore, FH modulated obesity-related effects on spatial navigation behaviour. In summary, an individual's genetic dementia risk influenced the impact of obesity on WM myelin and cognition. quantitative magnetization transfer, NODDI, white matter, myelin, parahippocampal cingulum 7 ResultsInsert Table 2 and Figures 2 and 3 here 2.1 Multivariate covariance analysis (MANCOVA) of white matter microstructural indices MANCOVA tested for the effects of APOE genotype (e4+, e4-), family history (FH+, FH-) and central obesity (WHR+, WHR-) on all microstructural indices (MPF, kf, R1, ISOSF, ICSF, ODI) in all white matter pathways (left PHC, right PHC, left UF, right UF, left CST, right CST and fornix) and WBWM regions whilst controlling for age, sex, and years of education. Omnibus effects: Main effects were observed for age [F(48,60) = 2.64, p < 0.001, hp 2 = 0.68] and sex [F(48,60) = 2.61, p < 0.001, hp 2 = 0.67]. Interaction effects were present between APOE and WHR [F(48,60) = 1.6, p = 0.04, hp 2 = 0.56] and between APOE, FH and WHR [F(48,60) = 1.7, p = 0.02, hp 2 = 0.58].Post-hoc effects: Ageing was associated with reductions in MPF, kf, and R1 in WBWM, fornix and right UF (Table 2). MPF and kf reductions were also present in the left UF and bilateral CST respectively. In addition, age-related increases in ISOSF were observed in WBWM and fornix and increases in ODI in the fornix (Table 2, Figure 2A).Women relative to men showed lower kf, ISOSF and ODI in WBWM and the fornix and larger fornix MPF (Table 2, Figure 2B). Two-way interaction effects between APOE and WHR were present for right PHC ( Figure 3A) and bilateral CST but additional post-hoc group comparisons to assess the directions of these effects were non-significant. Three-way interaction effects between FH, APOE and WHR were observed for MPF in WBWM, bilateral CST, bilateral UF and right PHC ( Figure 3B). For right PHC there was also an effect on ICSF. These three-way interaction effects were followed up by testing for APOE and WHR interactions in FH+ and FH-individuals separately ( Figure 3C). FH-individuals did not show any interaction effects B from the Alzheimer's Society and the BR...

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Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence

Cited by 263 publications

References 249 publications

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

Advance of sporadic Alzheimer's disease animal models

Genetic risk of dementia modifies the impact of obesity on limbic white matter and spatial navigation behavior in cognitively healthy adults

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