CIDeRplusGeneral Information:
| Id: | 7,322 |
| Diseases: |
Alzheimer disease
- [OMIM]
|
| Mammalia | |
| review | |
| Reference: | Mielke MM et al.(2014) Clinical epidemiology of Alzheimers disease: assessing sex and gender differences Clin Epidemiol 6: 37-48 [PMID: 24470773] |
Interaction Information:
| Comment | The prevalence of AD is significantly higher in women compared to men. Recent estimates suggest that almost two-thirds of the individuals diagnosed with AD are women. A reason for the higher prevalence among women may be that they live longer, on average, than men. From European and Asian populations have also observed a higher incidence in women after the age of 80‚Äď85 years. In contrast to these studies, the Cache County Study, did report a higher incidence of AD in men than women until age 78, after which women had a higher incidence than men. |
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Formal Description Interaction-ID: 71909 |
phenotype sex, female increases_activity of disease |
| Comment | Some studies suggest a higher prevalence of mild cognitive impairment (MCI) in men, while others suggest either a higher prevalence in women or no sex difference. In general, women have a higher incidence of MCI at older ages. Men consistently have a higher incidence of the non-amnestic type of MCI. |
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Formal Description Interaction-ID: 71916 |
phenotype sex, male increases_activity of phenotype mild cognitive impairment |
| Comment | The risk of dementia is higher in persons with MCI compared to cognitively normal individuals. |
|
Formal Description Interaction-ID: 71917 |
phenotype mild cognitive impairment increases_activity of disease Dementia |
| Comment | Incidence studies examining sex differences in AD are equivocal. The majority of studies conducted in the US have not observed sex differences in the rates of developing AD. |
|
Formal Description Interaction-ID: 71919 |
phenotype sex NOT affects_activity of disease |
| Comment | Men consistently have a higher incidence of the non-amnestic type of MCI. While amnestic MCI is considered prodromal for AD, non-amnestic MCI is considered prodromal for non-AD dementias, such as vascular dementia. |
|
Formal Description Interaction-ID: 71923 |
phenotype mild cognitive impairment, non-amnestic increases_activity of disease Dementia, non-AD |
| Comment | Non-amnestic MCI is considered prodromal for non-AD dementias, such as vascular dementia. |
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Formal Description Interaction-ID: 71924 |
|
| Comment | Men consistently have a higher incidence of the non-amnestic type of MCI. While amnestic MCI is considered prodromal for AD, non-amnestic MCI is considered prodromal for non-AD dementias, such as vascular dementia. |
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Formal Description Interaction-ID: 71935 |
phenotype mild cognitive impairment, non-amnestic increases_activity of disease Vascular dementia |
| Comment | Men consistently have a higher incidence of the non-amnestic type of MCI. While amnestic MCI is considered prodromal for AD, non-amnestic MCI is considered prodromal for non-AD dementias, such as vascular dementia. |
|
Formal Description Interaction-ID: 71936 |
phenotype sex, male increases_activity of phenotype mild cognitive impairment, non-amnestic |
| Comment | The most striking difference between the brain anatomy of men and women is the larger head size and cerebral brain volume in men (about 10%). |
|
Formal Description Interaction-ID: 71937 |
phenotype sex, male increases_activity of phenotype increased head size |
| Comment | The most striking difference between the brain anatomy of men and women is the larger head size and cerebral brain volume in men (about 10%). |
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Formal Description Interaction-ID: 71938 |
phenotype sex, male increases_activity of phenotype increased cerebral brain volume |
| Comment | In patients with MCI and AD, brain volumes have been found to decline faster in women than men, supporting the evidence of faster progression of women from MCI to AD. |
|
Formal Description Interaction-ID: 71939 |
phenotype sex, female increases_activity of phenotype brain volume decline |
| Comment | Women typically have a higher percentage of grey matter in several brain regions, whereas men have a higher percentage of white matter. |
|
Formal Description Interaction-ID: 71941 |
phenotype sex, male increases_quantity of tissue/cell line |
| Comment | Women typically have a higher percentage of grey matter in several brain regions, whereas men have a higher percentage of white matter. |
|
Formal Description Interaction-ID: 71942 |
phenotype sex, female increases_quantity of tissue/cell line |
| Comment | Men have more pronounced cerebral metabolic deficits compared to women at the same level of cognitive impairment, suggesting that the greater brain reserve in men may be helping them withstand more pathology than women at the same level of dementia severity. |
|
Formal Description Interaction-ID: 71943 |
phenotype sex affects_activity of phenotype cerebral metabolic deficits |
| Comment | The E4 allele of the apolipoprotein E (APOE) gene is the strongest known genetic risk factor for late-onset AD. Compared to non-carriers, heterozygous carriers of one E4 allele are 3‚Äď4 times more likely to develop AD, whereas the risk for homozygous carriers is even higher. The APOE E4 allele is specifically associated with an earlier age of onset of AD. |
|
Formal Description Interaction-ID: 71967 |
|
| Comment | The effects of the E4 genotype are more pronounced in women than in men. Three studies reported that women with one E4 allele had about a four-fold risk of AD, whereas men with one E4 allele showed little increased risk. |
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Formal Description Interaction-ID: 71968 |
phenotype sex, female increases_activity of gene/protein mutant |
| Comment | The APOE E4 allele has a greater deleterious effect on hippocampal pathology, functional connectivity changes in the default mode network, cortical thickness, and memory performance in women compared with men at different stages of AD. |
|
Formal Description Interaction-ID: 71969 |
gene/protein mutant decreases_activity of tissue/cell line |
| Comment | The APOE E4 allele has a greater deleterious effect on hippocampal pathology, functional connectivity changes in the default mode network, cortical thickness, and memory performance in women compared with men at different stages of AD. |
|
Formal Description Interaction-ID: 71970 |
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| Comment | The APOE E4 allele has a greater deleterious effect on hippocampal pathology, functional connectivity changes in the default mode network, cortical thickness, and memory performance in women compared with men at different stages of AD. |
|
Formal Description Interaction-ID: 71971 |
gene/protein mutant decreases_activity of process |
| Comment | A large autopsy study found that amyloid plaque and neurofibrillary tangle pathology was greatest among women who were E4 carriers. |
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Formal Description Interaction-ID: 71972 |
gene/protein mutant increases_quantity of phenotype |
| Comment | A large autopsy study found that amyloid plaque and neurofibrillary tangle pathology was greatest among women who were E4 carriers. |
|
Formal Description Interaction-ID: 71973 |
gene/protein mutant increases_quantity of phenotype |
| Comment | A large study consisting of 16 research centers worldwide (including 4,711 patients and 4,537 controls) reported that the Met66 allele of Brain Derived Neurotrophic Factor (BDNF) gene, which reduces the transport of BDNF, is associated with an increased risk of AD in women (odds ratio =1.14, 95% confidence interval 1.05‚Äď1.24, P=0.002), but not in men. This finding is biologically plausible since estrogen plays an important role in the expression of BDNF. Post-menopausal women with the MET66 allele would therefore have both reduced transport and expression of BDNF, thus causing an increased risk of AD. |
|
Formal Description Interaction-ID: 71974 |
gene/protein mutant increases_activity of disease |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
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Formal Description Interaction-ID: 71975 |
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| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
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Formal Description Interaction-ID: 71976 |
SNP increases_activity of disease |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
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Formal Description Interaction-ID: 71977 |
gene/protein mutant increases_activity of disease |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
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Formal Description Interaction-ID: 71978 |
gene/protein mutant increases_activity of disease |
| Comment | A diabetes-related gene, the G allele of NSP65 of the peroxisome proliferators-activated receptors gamma was associated with a significantly increased odds of AD in men, but a reduced odds in women. |
|
Formal Description Interaction-ID: 71979 |
gene/protein mutant affects_activity of disease |
| Comment | The 219K allele of the ATP Binding Cassette Transporter 1 (ABCA1) gene had a 1.75-fold increased risk of developing AD in women, but was found to be protective in men. |
|
Formal Description Interaction-ID: 71980 |
gene/protein mutant increases_activity of disease |
| Comment | A large study consisting of 16 research centers worldwide (including 4,711 patients and 4,537 controls) reported that the Met66 allele of Brain Derived Neurotrophic Factor (BDNF) gene, which reduces the transport of BDNF, is associated with an increased risk of AD in women (odds ratio =1.14, 95% confidence interval 1.05‚Äď1.24, P=0.002), but not in men. This finding is biologically plausible since estrogen plays an important role in the expression of BDNF. Post-menopausal women with the MET66 allele would therefore have both reduced transport and expression of BDNF, thus causing an increased risk of AD. |
|
Formal Description Interaction-ID: 71981 |
phenotype sex, female increases_activity of gene/protein mutant |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
|
Formal Description Interaction-ID: 71982 |
phenotype sex, male increases_activity of SNP |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
|
Formal Description Interaction-ID: 71983 |
phenotype sex, male increases_activity of SNP |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
|
Formal Description Interaction-ID: 71984 |
phenotype sex, male increases_activity of gene/protein mutant |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
|
Formal Description Interaction-ID: 71985 |
phenotype sex, male increases_activity of gene/protein mutant |
| Comment | A diabetes-related gene, the G allele of NSP65 of the peroxisome proliferators-activated receptors gamma was associated with a significantly increased odds of AD in men, but a reduced odds in women. |
|
Formal Description Interaction-ID: 71986 |
phenotype sex affects_activity of gene/protein mutant |
| Comment | The 219K allele of the ATP Binding Cassette Transporter 1 (ABCA1) gene had a 1.75-fold increased risk of developing AD in women, but was found to be protective in men. |
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Formal Description Interaction-ID: 71987 |
phenotype sex affects_activity of gene/protein mutant |
| Comment | sex and gender. |
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Formal Description Interaction-ID: 71988 |
phenotype sex cooccurs with phenotype sex, female |
| Comment | sex and gender. |
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Formal Description Interaction-ID: 71989 |
phenotype sex cooccurs with phenotype sex, male |
| Comment | Following menopause, women experience relatively rapid loss of the ovarian sex hormones 17 beta-estradiol and progesterone. |
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Formal Description Interaction-ID: 71996 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Following menopause, women experience relatively rapid loss of the ovarian sex hormones 17 beta-estradiol and progesterone. |
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Formal Description Interaction-ID: 71997 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 71998 |
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| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 72002 |
drug/chemical compound Estrogen decreases_activity of phenotype |
| Comment | The Mayo Clinic Cohort Study of Oophorectomy and Aging showed an almost doubled risk of dementia in women who underwent bilateral oophorectomy before menopause. |
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Formal Description Interaction-ID: 72003 |
environment oophorectomy increases_activity of disease Dementia |
| Comment | Women who initiated hormone replacement therapy (HRT) after the bilateral oophorectomy, and continued utilizing HRT at least until the age of natural menopause (approximately 51 years), did not experience an increased risk of AD. |
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Formal Description Interaction-ID: 72004 |
environment hormone replacement therapy decreases_activity of environment oophorectomy |
| Comment | The Women’s Health Initiative Memory Study (WHIMS), a large randomized clinical trial of HRT, reported a two-fold increased risk of dementia in women randomized to HRT after age 65 years. |
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Formal Description Interaction-ID: 72006 |
environment hormone replacement therapy increases_activity of disease Dementia |
| Comment | The use of hormone replacement therapy (HRT), when initiated around the time of menopause but not years after, reduces the risk of AD. In the Cache County Study, women who initiated HRT within 5 years of menopause had a 30% lower risk of AD compared to women who reported no use of HRT. Women who began hormone therapy more than 5 years after menopause did not have a lowered risk. |
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Formal Description Interaction-ID: 72008 |
environment hormone replacement therapy decreases_activity of disease |
| Comment | Women who began hormone replacement therapy (HRT) more than 5 years after menopause did not have a lowered risk of AD. In fact, those who started hormone use when they were 65 years or older had almost a two-fold increased risk of AD. |
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Formal Description Interaction-ID: 72015 |
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| Comment | The age of natural menopause is approximately 51 years. |
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Formal Description Interaction-ID: 72017 |
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| Comment | Long-term estrogen depletion (LTED) can cause decreased levels of estrogen receptor (ER)-alpha, in the CA1 region of the hippocampus, a highly responsive region to estrogen therapy, resulting in cognitive enhancement and neuroprotection. |
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Formal Description Interaction-ID: 72027 |
process response to long-term estrogen depletion decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for ESR1 |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72037 |
environment education affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72039 |
environment occupation affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72040 |
environment diet affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72041 |
environment exercise affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72042 |
environment smoking affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72043 |
environment drinking behavior affects_activity of phenotype sex |
| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72044 |
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| Comment | Specific factors related to gender identity that may contribute to the risk of AD include education, occupation, diet and exercise, and smoking and drinking behaviors. Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72045 |
environment cognitive activities affects_activity of phenotype sex |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72046 |
environment cognitive activities decreases_activity of process cognitive aging |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72047 |
environment higher education decreases_activity of process cognitive aging |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72048 |
environment occupation decreases_activity of process cognitive aging |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72049 |
environment cognitive activities increases_activity of process cognitive reserve |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72050 |
environment higher education increases_activity of process cognitive reserve |
| Comment | Gender is also strongly linked with the concept of cognitive reserve such that a higher education/occupation and greater engagement in cognitive activities provides higher reserve against disease and results in varying cognitive aging trajectories among individuals. |
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Formal Description Interaction-ID: 72051 |
environment occupation increases_activity of process cognitive reserve |
| Comment | Cognitive activities have been shown to reduce the risk of dementia in the elderly. |
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Formal Description Interaction-ID: 72053 |
environment cognitive activities decreases_activity of disease Dementia |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72054 |
process intelligence quotient affects_activity of process cognitive function |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72055 |
process intelligence quotient affects_activity of disease Dementia |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72056 |
process intelligence quotient affects_activity of process mortality |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72057 |
process mental ability affects_activity of process cognitive function |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72058 |
process mental ability affects_activity of disease Dementia |
| Comment | Low childhood mental ability and IQ is associated with lower cognitive ability in late-life, with an increased risk of dementia, and with increased mortality. |
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Formal Description Interaction-ID: 72059 |
process mental ability affects_activity of process mortality |
| Comment | One study of over 9,000 women collected self-reported information on physical activity when the women were in their teens, age 30, age 50, and in later-life. Physical activity at all time points was associated with a reduced risk of cognitive impairment in late-life. However, physical activity in the teenage years was associated with the greatest reduction in risk. Women who were not active as teenagers, but who were physically active at age 30 and 50, also had a reduced risk, but not as much as those who were active as teenagers. Among women who were physically active as teenagers, late-life physical activity did not appear to further reduce the risk of cognitive impairment, suggesting that early activity, when the brain is developing, may be most important. |
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Formal Description Interaction-ID: 72060 |
environment exercise decreases_activity of phenotype cognitive impairment |
| Comment | Long-term estrogen depletion (LTED) can cause decreased levels of estrogen receptor (ER)-alpha, in the CA1 region of the hippocampus, a highly responsive region to estrogen therapy, resulting in cognitive enhancement and neuroprotection. |
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Formal Description Interaction-ID: 72061 |
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| Drugbank entries | Show/Hide entries for ESR1 |
| Comment | Long-term estrogen depletion (LTED) can cause decreased levels of estrogen receptor (ER)-alpha, in the CA1 region of the hippocampus, a highly responsive region to estrogen therapy, resulting in cognitive enhancement and neuroprotection. |
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Formal Description Interaction-ID: 72062 |
drug/chemical compound Estrogen increases_activity of tissue/cell line |
| Comment | Long-term estrogen depletion (LTED) can cause decreased levels of estrogen receptor (ER)-alpha, in the CA1 region of the hippocampus, a highly responsive region to estrogen therapy, resulting in cognitive enhancement and neuroprotection. |
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Formal Description Interaction-ID: 72063 |
drug/chemical compound Estrogen increases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for ESR1 |
| Comment | Acetylcholine is a neurotransmitter that is decreased in Alzheimer’s patients. |
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Formal Description Interaction-ID: 72068 |
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| Drugbank entries | Show/Hide entries for Acetylcholine |
| Comment | Acetylcholine is a neurotransmitter that is decreased in Alzheimer’s patients. |
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Formal Description Interaction-ID: 72070 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Nicotinic acetylcholine receptors are especially reduced in AD. Therefore, it was hypothesized that nicotine could be used to prevent or delay the progression of AD, and that smoking may be associated with a reduced risk of AD. Although it is possible that nicotine could be beneficial for AD, cigarette smoking contains several other toxins, has carcinogenic effects, is a known risk factor for cardiovascular and pulmonary disease, and therefore may increase the risk of AD. Additionally, many smokers also drink, and the interaction between cigarette smoking and heavy alcohol use may be especially detrimental for cognition. The differential changes in smoking by gender may impact the subsequent incidence rate of AD among women and men. |
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Formal Description Interaction-ID: 72071 |
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| Comment | The effects of the E4 genotype are more pronounced in women than in men. Three studies reported that women with one E4 allele had about a four-fold risk of AD, whereas men with one E4 allele showed little increased risk. |
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Formal Description Interaction-ID: 72092 |
gene/protein mutant increases_activity of disease |
| Comment | A bilateral oophorectomy prior to menopause causes an abrupt deficiency of estrogen, progesterone, testosterone, and a disruption of the hypothalamic‚Äďpituitary‚Äďovarian axis. |
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Formal Description Interaction-ID: 85050 |
environment oophorectomy decreases_quantity of drug/chemical compound Estrogen |
| Comment | A bilateral oophorectomy prior to menopause causes an abrupt deficiency of estrogen, progesterone, testosterone, and a disruption of the hypothalamic‚Äďpituitary‚Äďovarian axis. |
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Formal Description Interaction-ID: 85051 |
environment oophorectomy decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | A bilateral oophorectomy prior to menopause causes an abrupt deficiency of estrogen, progesterone, testosterone, and a disruption of the hypothalamic‚Äďpituitary‚Äďovarian axis. |
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Formal Description Interaction-ID: 85052 |
environment oophorectomy decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | A bilateral oophorectomy prior to menopause causes an abrupt deficiency of estrogen, progesterone, testosterone, and a disruption of the hypothalamic‚Äďpituitary‚Äďovarian axis. |
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Formal Description Interaction-ID: 85053 |
environment oophorectomy decreases_activity of drug/chemical compound HPO axis |
| Comment | Women who initiated hormone replacement therapy (HRT) after the bilateral oophorectomy, and continued utilizing HRT at least until the age of natural menopause (approximately 51 years), did not experience an increased risk of AD. |
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Formal Description Interaction-ID: 85054 |
environment hormone replacement therapy NOT increases_activity of disease |
| Comment | Observational studies generally report reduced risks of AD in women who initiate HRT within a short period (typically ,3 years) after natural menopause and after oophorectomy performed prior to menopause. |
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Formal Description Interaction-ID: 85055 |
environment hormone replacement therapy decreases_activity of disease |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115232 |
drug/chemical compound Estrogen increases_activity of process synapse formation |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115233 |
drug/chemical compound Estrogen increases_activity of process maintaining hippocampal function during aging |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115234 |
drug/chemical compound Estrogen increases_activity of phenotype |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115235 |
drug/chemical compound Estrogen increases_activity of process |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115236 |
drug/chemical compound Estrogen increases_activity of gene/protein |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115237 |
drug/chemical compound Estrogen decreases_quantity of phenotype |
| Comment | Animal and cellular models have consistently shown the neuroprotective effects of estrogen which include: improving synapse formation on hippocampal dendritic spines, maintaining hippocampal function during aging; improving cerebral blood flow and glucose metabolism, increasing choline acetyltransferase activity in the basal forebrain and hippocampus (choline acetyltransferase is involved in the synthesis of acetylcholine, a neurotransmitter reduced in AD and implicated in memory function), reducing the aggregation of amyloid-beta and associated neurotoxicity, and preventing mitochondrial damage. |
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Formal Description Interaction-ID: 115238 |
drug/chemical compound Estrogen decreases_activity of process |
| Comment | The effects of the E4 genotype are more pronounced in women than in men. Three studies reported that women with one E4 allele had about a four-fold risk of AD, whereas men with one E4 allele showed little increased risk. |
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Formal Description Interaction-ID: 124712 |
phenotype sex, male decreases_activity of gene/protein mutant |
| Comment | SNPs found to pose a risk of AD among men, but not women, include a SNP (rs688) of the low-density lipoprotein receptor and functional apolipoprotein E receptor, the rs17571 SNP of the lysosomal protease cathepsin D, SOS2 (involved in signal transduction pathways, including insulin signaling), and PCK1 (catalyzes the first step in hepatic gluconeogenesis). |
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Formal Description Interaction-ID: 140209 |
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| Drugbank entries | Show/Hide entries for LDLR |