A link to a Alz article that is dry and too long in my opinion but some good in it.
https://content.iospress.com/articles/journal.../jad171145
Some info from the link that I liked,
Fletch
Diet:
There is considerable evidence that all these conditions linked to AD can be ameliorated by dietary changes. High calorie diets, which contain significant amounts of processed carbohydrates, simple sugars, processed fats, and which are low in fiber, vitamins, minerals, antioxidants, and healthy fats, are strongly linked to obesity, T2D, hypertension, insulin resistance, and cardiovascular disease. In contrast, adherence to a traditional Mediterranean diet (MeDi) [8] is known to be associated with longevity and good health [192]; similarly, the traditional Okinawa diet, along with an active and social lifestyle, is also associated with longevity and good health [193]. The MeDi is characterized by a high intake of vegetables, legumes, fruits, cereals, fish and unsaturated fatty acids (mostly in the form of olive oil), low intake of saturated fatty acids, meat, and poultry, low-to-moderate intake of dairy products (mostly cheese and yoghurt), and a regular but moderate amount of alcohol (mostly wine and generally with meals).
As part of the longitudinal AIBL studies, we investigated the dietary patterns of participants via questionnaires. In one study, adherence to the MeDi (based on a score of 0–9 for adherence) was greater in the healthy control participants compared to the MCI and AD subjects, with a greater difference observed between AD and healthy control subjects (p < 0.001) [194]. In a subsequent analysis only looking at healthy control participants, MeDi, western and prudent dietary patterns were investigated in relation to cognitive change using a global cognitive score, as well as six cognitive domains, over 36 months. The western and prudent dietary patterns reflect actual dietary intakes observed in a given population, independent of any assumption on their beneficial or harmful effect. Our western dietary pattern was heavily loaded with red and processed meats, chips, refined grains, potatoes, sweets, and condiments, while our prudent dietary pattern was loaded heavily with vegetables, fruits, and nuts. The cohort of 527 cognitively healthy older adults completed the Cancer Council of Victoria food frequency questionnaire at baseline, and underwent a comprehensive neuropsychological battery at baseline and two follow-ups. Higher adherence to the MeDi was associated with less decline in the executive function cognitive domain in APOE ɛ4 allele carriers (β= 0.077; p < 0.001), and a higher adherence to the western diet was associated with increased decline in the visuospatial functioning domain in APOE ɛ4 allele non-carriers (β= –0.0006; p < 0.01). [195]. No significant relationships were observed between prudent diet score and cognitive decline. We hypothesized that the oily fish component of the MeDi (the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid found in oily fish) may be mediating the effects observed via a mechanism involving inflammation.
Various other studies carried out in our laboratories have shown links between dyslipidemia and AD. For example, in a small study, plasma Aβ42 levels were found to correlate with body mass index in healthy people [196]. The study also found (non-significant) associations with insulin levels, HDL, and the inflammatory marker C-reactive protein, thus larger longitudinal studies are required to determine the significance of the results. We have also shown that plasma Aβ40 and Aβ42 were lower in individuals with T2D compared to others from the same community-based cohort without diabetes [183]. The Aβ42: Aβ40 ratio was also significantly higher in those with diabetes. Apart from showing an association between plasma Aβ levels and T2D, such variation needs to be considered when assessing plasma Aβ peptides as AD biomarkers.
Most recently, we have found that serum HDL is associated with better cognitive function, in particular short and long delay-free recalls, in older women (average age 62.5) [197]. This positive effect of HDL on verbal memory warrants further investigation in longitudinal studies, and since lipid intake is a major factor influencing HDL levels, this is further evidence of the importance of diet on AD and cognitive decline.
As oxidative stress and inflammation are thought to be central phenomena in the early pathogenesis of AD (as well as other conditions linked to AD), dietary supplements, or dietary changes that may increase antioxidant or anti-inflammatory compound intake, and reduce the intake of oxidized and processed lipids and proteins, have been recommended. We have reviewed a number of these recommended dietary supplements and changes. For example, we have reviewed tea as it has been suggested to contain potent antioxidants: it is rich in phytochemicals including flavonoids, tannins, caffeine, polyphenols, boheic acid, theophylline, theobromine, anthocyanins, gallic acid, and in particular epigallocatechin-3-gallate. Studies have shown that catechins (flavonoid phytochemicals) may inhibit Aβ plaque formation, and enhance cognitive function [198]. Further studies of tea are warranted, to determine more clearly any benefits of the components in reducing AD risk.
Other antioxidant and anti-inflammatory food sources that have also been investigated by us and others include curcumin (a component of the spice turmeric), cinnamon, ginger, and the pepper family [25, 199]. We have investigated the ability of a curcumin formulation (BiocurcumaxTM) in a 12-month study involving community-dwelling older adults. The main finding was a significant time×treatment group interaction observed for the Montreal Cognitive Assessment, which was subsequently revealed to be driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. Further longitudinal assessment is required to investigate changes in cognitive outcome [200]. Other clinical studies have also failed to find significant improvement following supplementation with curcumin, thought to be partly due to low solubility and bioavailability, and also due to cohorts already having AD, which is likely to be at a stage too late to produce significant positive effects, due to considerable neuronal loss already being present. Nevertheless, as described in our review [201], in vitro studies have indicated that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and dementia development, most likely due to antioxidant and anti-inflammatory properties.
High carbohydrate diets are thought to contribute to insulin resistance, which is associated with a host of peripheral changes that can all impact on AD pathogenesis, including hyperglycemia, hyperinsulinemia, dyslipidemia, and inflammation [168]. In addition, we have recently shown greater carbohydrate intake to be associated with poorer performance in verbal memory in APOE ɛ4 allele non-carriers, and poorer performance in attention in APOE ɛ4 allele carriers [202]. These findings suggest that lowering carbohydrate intake may offer neurocognitive benefits, with our study suggesting specific cognitive domains are affected in an APOE genotype-dependent manner; however, all these findings need validation in longitudinal studies.
Due to the low glucose usage in the brain in the very early stages of AD, we are investigating the potential benefits of adding a modified version of coconut oil to the diet, or more likely replacing some other dietary fat with some coconut fat. Unlike the fats in most other dietary fat sources, a significant amount of lipids in coconut oil consists of medium chain fatty acids, which may be converted to ketone bodies, which in turn can provide an alternative energy source to the brain. There is already mounting evidence that coconut oil may be beneficial in the treatment of obesity, dyslipidemia, elevated LDL, insulin resistance, and hypertension (all risk factors for AD), and certain phenolic compounds and hormones (cytokinins) found in coconut may help prevent the aggregation of Aβ [203]. However, some studies question the cardiovascular benefits of coconut oil, and in fact argue that it is detrimental to cardiovascular health. More definite conclusions as to its clinical significance particularly with respect to brain health must await findings from randomized controlled trials.
Physical activity
Numerous studies have reported positive impacts of physical activity on cognitive function [204, 205]. However, the majority of previous studies have relied on self-report questionnaires, which by nature may introduce reporting biases. To remove this source of potential bias, we investigated habitual physical activity levels (quantified from actigraphy units worn for seven days) undertaken by 217 cognitively healthy participants from the AIBL cohort, aged 60–89. Actigraphy units measure total physical activity and intensity of physical activity, and the cohort was split into tertiles based on physical activity intensity. Comprehensive neuropsychological assessment was also carried out, and participants in the highest tertiles of intensity were found to be performing significantly better on the digit symbol, Rey Complex Figure Test copy, and verbal fluency tests, compared with the lowest tertile [206]. Nevertheless, when the cohort was split into tertiles based on total amount of physical activity, no differences in cognitive performance were observed, indicating that intensity may be more relevant in the association between physical activity and cognitive function.
We have also examined the relationship between habitual physical activity levels and neuroimaging biomarkers. In particular, we investigated the relationship between self-reported physical activity levels and hippocampal volume in a sub-cohort of AIBL study cognitively healthy participants. We observed that participants reporting the highest levels of habitual physical activity had the largest hippocampal volume [207]. In this study, we also examined the effect of the brain-derived neurotrophic factor polymorphism (BDNF Val66Met) on this relationship: We observed that only Val/Val homozygotes (i.e., those we assume not to have impaired function of BDNF on hippocampal neurons) received the benefit of physical activity in terms of larger hippocampal volume, whereas Met carriers (i.e., those more likely to have impaired action of BDNF on hippocampal neurons) did not have an association between physical activity levels and hippocampal volume.
We have also used questionnaires to investigate exercise levels in a subset of the DIAN cohort. In 139 pre-symptomatic mutation carriers, the relationships between self-reported exercise levels and brain NAB, CSF Aβ42, and tau levels were evaluated. No differences between NAB, CSF Aβ42 or tau levels were observed between low and high exercise groups. However, when examining only those deemed to be accumulating NAB, low exercisers had higher mean NAB levels than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset (EYO) was a significant predictor of brain NAB [208]; whereby the relationship between NAB and EYO was marked in low exercisers, and the expected strong relationship between NAB and EYO was not observed in high exercisers. Whether higher levels of exercise are associated with protection against NAB accumulation, or whether decreases in exercise levels are a symptom of developing dementia, or a combination of the two, is yet to be determined. Nevertheless, regular exercise should be recommended to all older adults (and indeed anyone at increased risk of AD) as a vast array of literature indicates that it leads to improvements in physical health, a reduction in frailty, the lowering of depression, and short or long-term improvements in cognitive function [209–212].
Sleep
Another aspect of lifestyle which is gaining interest in the field of AD research is sleep. Importantly, it is becoming apparent that rather than simply manifesting as a comorbidity of AD, suboptimal sleep actually appears to contribute both to cognitive decline and AD pathology, as discussed in our review which details the proposed bidirectional relationship between suboptimal sleep and AD pathology [213]. Numerous studies have linked suboptimal sleep to faster cognitive decline and increased AD and dementia risk [214, 215]. A recent systematic review and meta-analysis of 18 longitudinal studies indicates that insomnia, in particular, is linked to an increased risk of AD [216]. Furthermore, as part of the AIBL study, we investigated the relationship between sleep quality and PET-determined brain Aβ burden in cognitively normal individuals. We found longer sleep latency to be associated with higher brain Aβ burden, with a 30-minute longer sleep latency potentially translating to an equivalent of 2 years of brain Aβ accumulation [217]. Interestingly, in our cohort, APOE ɛ4 allele status had no effect on this relationship. However, our additional investigations using the AIBL study cohort suggest that genetic variation in the cerebrally expressed water-channel protein, Aquaporin-4, does moderate the relationship between sleep and brain Aβ burden (Rainey-Smith SR et al., Translational Psychiatry, in press), an intriguing finding given that Aquaporin-4 is an astrocytic end-feet expressed water channel protein postulated to be involved in glymphatic system-mediated clearance of Aβ from the brain [218]. Further studies, particularly longitudinal follow-up studies, are needed to gain greater insight into the extent sleep deprivation can influence cognitive decline.
Some other sleep investigations have involved the analysis of electroencephalograms (EEG) for both wakefulness and rapid eye movement (REM) sleep, performed over the temporal regions of AD patients and age-matched control subjects. Analysis of the spectra indicated that AD patients had much slower EEG readings during REM sleep when compared to being awake, and asymmetry on the awake EEG of AD patients was found to be even more prominent than on the REM sleep EEG [219].
https://content.iospress.com/articles/journal.../jad171145
Some info from the link that I liked,
Fletch
Diet:
There is considerable evidence that all these conditions linked to AD can be ameliorated by dietary changes. High calorie diets, which contain significant amounts of processed carbohydrates, simple sugars, processed fats, and which are low in fiber, vitamins, minerals, antioxidants, and healthy fats, are strongly linked to obesity, T2D, hypertension, insulin resistance, and cardiovascular disease. In contrast, adherence to a traditional Mediterranean diet (MeDi) [8] is known to be associated with longevity and good health [192]; similarly, the traditional Okinawa diet, along with an active and social lifestyle, is also associated with longevity and good health [193]. The MeDi is characterized by a high intake of vegetables, legumes, fruits, cereals, fish and unsaturated fatty acids (mostly in the form of olive oil), low intake of saturated fatty acids, meat, and poultry, low-to-moderate intake of dairy products (mostly cheese and yoghurt), and a regular but moderate amount of alcohol (mostly wine and generally with meals).
As part of the longitudinal AIBL studies, we investigated the dietary patterns of participants via questionnaires. In one study, adherence to the MeDi (based on a score of 0–9 for adherence) was greater in the healthy control participants compared to the MCI and AD subjects, with a greater difference observed between AD and healthy control subjects (p < 0.001) [194]. In a subsequent analysis only looking at healthy control participants, MeDi, western and prudent dietary patterns were investigated in relation to cognitive change using a global cognitive score, as well as six cognitive domains, over 36 months. The western and prudent dietary patterns reflect actual dietary intakes observed in a given population, independent of any assumption on their beneficial or harmful effect. Our western dietary pattern was heavily loaded with red and processed meats, chips, refined grains, potatoes, sweets, and condiments, while our prudent dietary pattern was loaded heavily with vegetables, fruits, and nuts. The cohort of 527 cognitively healthy older adults completed the Cancer Council of Victoria food frequency questionnaire at baseline, and underwent a comprehensive neuropsychological battery at baseline and two follow-ups. Higher adherence to the MeDi was associated with less decline in the executive function cognitive domain in APOE ɛ4 allele carriers (β= 0.077; p < 0.001), and a higher adherence to the western diet was associated with increased decline in the visuospatial functioning domain in APOE ɛ4 allele non-carriers (β= –0.0006; p < 0.01). [195]. No significant relationships were observed between prudent diet score and cognitive decline. We hypothesized that the oily fish component of the MeDi (the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid found in oily fish) may be mediating the effects observed via a mechanism involving inflammation.
Various other studies carried out in our laboratories have shown links between dyslipidemia and AD. For example, in a small study, plasma Aβ42 levels were found to correlate with body mass index in healthy people [196]. The study also found (non-significant) associations with insulin levels, HDL, and the inflammatory marker C-reactive protein, thus larger longitudinal studies are required to determine the significance of the results. We have also shown that plasma Aβ40 and Aβ42 were lower in individuals with T2D compared to others from the same community-based cohort without diabetes [183]. The Aβ42: Aβ40 ratio was also significantly higher in those with diabetes. Apart from showing an association between plasma Aβ levels and T2D, such variation needs to be considered when assessing plasma Aβ peptides as AD biomarkers.
Most recently, we have found that serum HDL is associated with better cognitive function, in particular short and long delay-free recalls, in older women (average age 62.5) [197]. This positive effect of HDL on verbal memory warrants further investigation in longitudinal studies, and since lipid intake is a major factor influencing HDL levels, this is further evidence of the importance of diet on AD and cognitive decline.
As oxidative stress and inflammation are thought to be central phenomena in the early pathogenesis of AD (as well as other conditions linked to AD), dietary supplements, or dietary changes that may increase antioxidant or anti-inflammatory compound intake, and reduce the intake of oxidized and processed lipids and proteins, have been recommended. We have reviewed a number of these recommended dietary supplements and changes. For example, we have reviewed tea as it has been suggested to contain potent antioxidants: it is rich in phytochemicals including flavonoids, tannins, caffeine, polyphenols, boheic acid, theophylline, theobromine, anthocyanins, gallic acid, and in particular epigallocatechin-3-gallate. Studies have shown that catechins (flavonoid phytochemicals) may inhibit Aβ plaque formation, and enhance cognitive function [198]. Further studies of tea are warranted, to determine more clearly any benefits of the components in reducing AD risk.
Other antioxidant and anti-inflammatory food sources that have also been investigated by us and others include curcumin (a component of the spice turmeric), cinnamon, ginger, and the pepper family [25, 199]. We have investigated the ability of a curcumin formulation (BiocurcumaxTM) in a 12-month study involving community-dwelling older adults. The main finding was a significant time×treatment group interaction observed for the Montreal Cognitive Assessment, which was subsequently revealed to be driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. Further longitudinal assessment is required to investigate changes in cognitive outcome [200]. Other clinical studies have also failed to find significant improvement following supplementation with curcumin, thought to be partly due to low solubility and bioavailability, and also due to cohorts already having AD, which is likely to be at a stage too late to produce significant positive effects, due to considerable neuronal loss already being present. Nevertheless, as described in our review [201], in vitro studies have indicated that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and dementia development, most likely due to antioxidant and anti-inflammatory properties.
High carbohydrate diets are thought to contribute to insulin resistance, which is associated with a host of peripheral changes that can all impact on AD pathogenesis, including hyperglycemia, hyperinsulinemia, dyslipidemia, and inflammation [168]. In addition, we have recently shown greater carbohydrate intake to be associated with poorer performance in verbal memory in APOE ɛ4 allele non-carriers, and poorer performance in attention in APOE ɛ4 allele carriers [202]. These findings suggest that lowering carbohydrate intake may offer neurocognitive benefits, with our study suggesting specific cognitive domains are affected in an APOE genotype-dependent manner; however, all these findings need validation in longitudinal studies.
Due to the low glucose usage in the brain in the very early stages of AD, we are investigating the potential benefits of adding a modified version of coconut oil to the diet, or more likely replacing some other dietary fat with some coconut fat. Unlike the fats in most other dietary fat sources, a significant amount of lipids in coconut oil consists of medium chain fatty acids, which may be converted to ketone bodies, which in turn can provide an alternative energy source to the brain. There is already mounting evidence that coconut oil may be beneficial in the treatment of obesity, dyslipidemia, elevated LDL, insulin resistance, and hypertension (all risk factors for AD), and certain phenolic compounds and hormones (cytokinins) found in coconut may help prevent the aggregation of Aβ [203]. However, some studies question the cardiovascular benefits of coconut oil, and in fact argue that it is detrimental to cardiovascular health. More definite conclusions as to its clinical significance particularly with respect to brain health must await findings from randomized controlled trials.
Physical activity
Numerous studies have reported positive impacts of physical activity on cognitive function [204, 205]. However, the majority of previous studies have relied on self-report questionnaires, which by nature may introduce reporting biases. To remove this source of potential bias, we investigated habitual physical activity levels (quantified from actigraphy units worn for seven days) undertaken by 217 cognitively healthy participants from the AIBL cohort, aged 60–89. Actigraphy units measure total physical activity and intensity of physical activity, and the cohort was split into tertiles based on physical activity intensity. Comprehensive neuropsychological assessment was also carried out, and participants in the highest tertiles of intensity were found to be performing significantly better on the digit symbol, Rey Complex Figure Test copy, and verbal fluency tests, compared with the lowest tertile [206]. Nevertheless, when the cohort was split into tertiles based on total amount of physical activity, no differences in cognitive performance were observed, indicating that intensity may be more relevant in the association between physical activity and cognitive function.
We have also examined the relationship between habitual physical activity levels and neuroimaging biomarkers. In particular, we investigated the relationship between self-reported physical activity levels and hippocampal volume in a sub-cohort of AIBL study cognitively healthy participants. We observed that participants reporting the highest levels of habitual physical activity had the largest hippocampal volume [207]. In this study, we also examined the effect of the brain-derived neurotrophic factor polymorphism (BDNF Val66Met) on this relationship: We observed that only Val/Val homozygotes (i.e., those we assume not to have impaired function of BDNF on hippocampal neurons) received the benefit of physical activity in terms of larger hippocampal volume, whereas Met carriers (i.e., those more likely to have impaired action of BDNF on hippocampal neurons) did not have an association between physical activity levels and hippocampal volume.
We have also used questionnaires to investigate exercise levels in a subset of the DIAN cohort. In 139 pre-symptomatic mutation carriers, the relationships between self-reported exercise levels and brain NAB, CSF Aβ42, and tau levels were evaluated. No differences between NAB, CSF Aβ42 or tau levels were observed between low and high exercise groups. However, when examining only those deemed to be accumulating NAB, low exercisers had higher mean NAB levels than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset (EYO) was a significant predictor of brain NAB [208]; whereby the relationship between NAB and EYO was marked in low exercisers, and the expected strong relationship between NAB and EYO was not observed in high exercisers. Whether higher levels of exercise are associated with protection against NAB accumulation, or whether decreases in exercise levels are a symptom of developing dementia, or a combination of the two, is yet to be determined. Nevertheless, regular exercise should be recommended to all older adults (and indeed anyone at increased risk of AD) as a vast array of literature indicates that it leads to improvements in physical health, a reduction in frailty, the lowering of depression, and short or long-term improvements in cognitive function [209–212].
Sleep
Another aspect of lifestyle which is gaining interest in the field of AD research is sleep. Importantly, it is becoming apparent that rather than simply manifesting as a comorbidity of AD, suboptimal sleep actually appears to contribute both to cognitive decline and AD pathology, as discussed in our review which details the proposed bidirectional relationship between suboptimal sleep and AD pathology [213]. Numerous studies have linked suboptimal sleep to faster cognitive decline and increased AD and dementia risk [214, 215]. A recent systematic review and meta-analysis of 18 longitudinal studies indicates that insomnia, in particular, is linked to an increased risk of AD [216]. Furthermore, as part of the AIBL study, we investigated the relationship between sleep quality and PET-determined brain Aβ burden in cognitively normal individuals. We found longer sleep latency to be associated with higher brain Aβ burden, with a 30-minute longer sleep latency potentially translating to an equivalent of 2 years of brain Aβ accumulation [217]. Interestingly, in our cohort, APOE ɛ4 allele status had no effect on this relationship. However, our additional investigations using the AIBL study cohort suggest that genetic variation in the cerebrally expressed water-channel protein, Aquaporin-4, does moderate the relationship between sleep and brain Aβ burden (Rainey-Smith SR et al., Translational Psychiatry, in press), an intriguing finding given that Aquaporin-4 is an astrocytic end-feet expressed water channel protein postulated to be involved in glymphatic system-mediated clearance of Aβ from the brain [218]. Further studies, particularly longitudinal follow-up studies, are needed to gain greater insight into the extent sleep deprivation can influence cognitive decline.
Some other sleep investigations have involved the analysis of electroencephalograms (EEG) for both wakefulness and rapid eye movement (REM) sleep, performed over the temporal regions of AD patients and age-matched control subjects. Analysis of the spectra indicated that AD patients had much slower EEG readings during REM sleep when compared to being awake, and asymmetry on the awake EEG of AD patients was found to be even more prominent than on the REM sleep EEG [219].
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