Apolipoprotein E genotypes and longevity across dementia disorders

Skillbäck, Tobias; Lautner, Ronald; Mattsson, Niklas; Schott, Jonathan M.; Skoog, Ingmar; Nägga, Katarina; Kilander, Lena; Wimo, Anders; Winblad, Bengt; Eriksdotter, Maria; Blennow, Kaj; Zetterberg, Henrik

doi:10.1016/j.jalz.2018.02.003

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…32,33 In our cohort, statins were taken by 14%, and only in those on antihypertensive medications (27%), while antidiabetics were taken by only 4% of the cohort, making it unlikely that either type of medication contributed significantly to the association of antihypertensive medication use with reduced progression of AD neuropathology. Apolipoprotein E (APOE) ε4 genotype has also been associated with increased rather than decreased AD neuropathology, [34][35][36] and this was also the case in our cohort (89% of those with ε4 genotype had AD neuropathology). The small cohort of not AD APOE ε4 cases that were not medicated (<3) does not allow for statistical modelling of the influence of this factor.…”

Section: Discussionsupporting

confidence: 71%

Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation

Affleck

Sachdev

Stevens

et al. 2020

A&D Transl Res & Clin Interv

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Introduction Mounting evidence supports an association between antihypertensive medication use and reduced risk of Alzheimer's disease (AD). Consensus on possible pathological mechanisms remains elusive. Methods Human brain tissue from a cohort followed to autopsy that included 96 cases of AD (46 medicated for hypertension) and 53 pathological controls (33 also medicated) matched for cerebrovascular disease was available from the New South Wales Brain Banks. Quantified frontal cortex amyloid beta (Aβ) and tau proteins plus Alzheimer's neuropathologic change scores were analyzed. Results Univariate analyses found no difference in amounts of AD proteins in the frontal cortex between medication users, but multivariate analyses showed that antihypertensive medication use was associated with a less extensive spread of AD proteins throughout the brain. Discussion The heterogeneous nature of the antihypertensive medications is consistent with downstream beneficial effects of blood pressure lowering and/or management being associated with the reduced spreading of AD pathology observed.

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Section: Discussionsupporting

confidence: 71%

Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation

Affleck

Sachdev

Stevens

et al. 2020

A&D Transl Res & Clin Interv

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“…Despite the association of APOE genotype with life expectancy [22], its association with mortality in AD patients remains unclear [23]. We found no significant effect of APOE genotype on mortality, a finding that is consistent with those of several other previous studies [21, 24].…”

Section: Discussionsupporting

confidence: 92%

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

et al. 2019

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Objective Alzheimer’s disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10 years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD patients with high probability of AD physiopathology process assessed by positivity of three CSF biomarkers. Methods Three hundred twenty-one AD patients with abnormal values for CSF beta-amyloid peptide (Aβ42), tau, and phosphorylated tau levels were recruited from a memory clinic-based registry between 2008 and 2017 (Lariboisiere hospital, Paris, France) and followed during a median period of 3.9 years. We used multivariable Cox models to estimate the hazard ratio (HR) of death and institutionalization for baseline clinical data, genotype of the apolipoprotein E ( APOE ), and levels of CSF biomarkers. Results A total of 71 (22%) patients were institutionalized and 57 (18%) died during the follow-up. Greater age, male sex, lower MMSE score, and lower CSF Aβ42 level were associated with an increased risk of mortality. One standard deviation lower CSF Aβ42 (135 pg/mL) was associated with a 89% increased risk of death (95% CI = 1.25–2.86; p = 0.002). This association was not modified by age, sex, education, APOE ε4, and disease severity. There was no evidence of an association of tau CSF biomarkers with mortality. None of the CSF biomarkers were associated with institutionalization. Conclusions Lower CSF Aβ42 is a strong prognostic marker of mortality in AD patients, independently of age or severity of the disease. Whether drugs targeting beta-amyloid peptide could have an effect on mortality of AD patients should be investigated in future clinical trials.

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“…The symptoms of CADASIL include smaller cerebral vessels which in turn cause strokes, mood disturbances, and of course VaD ( Dichgans, 2002 ). The other gene attributed as a risk factor for VaD is APOE and its variants ( Skillbäck et al, 2018 ; Montagne et al, 2020 ). APOE has different variants denoted by e2 (APOE2), e3 (APOE3), and e4 (APOE4).…”

Section: Sex-specific Differences In Vadmentioning

confidence: 99%

Vascular Dementia and Underlying Sex Differences

Akhter

Persaud

Zaokari

et al. 2021

Front. Aging Neurosci.

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Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD); where Alzheimer’s accounts for 60–70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.

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Apolipoprotein E genotypes and longevity across dementia disorders

Abstract: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.

Cited by 9 publications

References 48 publications

Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation

Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

Vascular Dementia and Underlying Sex Differences

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