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Alzheimer’s delayed 4.7 years by high Omega-3 index (7.6 years if also have APOE-4) June - 2022


Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study

Nutrients 2022, 14(12), 2408; https://doi.org/10.3390/nu14122408
by Aleix Sala-Vila 1,2,*,†ORCID,Claudia L. Satizabal 3,4,5,6,†,Nathan Tintle 1,7,Debora Melo van Lent 3,4,5,6ORCID,Ramachandran S. Vasan 8,Alexa S. Beiser 9,Sudha Seshadri 3,4,5,6 andWilliam S. Harris 1,10ORCID

High DHA, reduces incidence of dementia

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High Omega-3 index: delays Alz 7.6 years, Dementia 7.3 years


Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with incident AD, testing for an interaction with APOE-ε4 carriership. During the follow-up (median, 7.2 years), 131 cases of AD were documented. In fully adjusted models, risk for incident AD in the highest RBC DHA quintile (Q5) was 49% lower compared with the lowest quintile (Q1) (Hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.27, 0.96). An increase in RBC DHA from Q1 to Q5 was predicted to provide an estimated 4.7 additional years of life free of AD. We observed an interaction DHA × APOE-ε4 carriership for AD. Borderline statistical significance for a lower risk of AD was observed per standard deviation increase in RBC DHA (HR: 0.71, 95% CI: 0.51, 1.00, p = 0.053) in APOE-ε4 carriers, but not in non-carriers (HR: 0.85, 95% CI: 0.65, 1.11, p = 0.240). These findings add to the increasing body of literature suggesting a robust association worth exploring dietary DHA as one strategy to prevent or delay AD.
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Discussion

In this prospective study conducted in a community-based sample of Americans over age 65 who were followed for a median of 7.2 years for incident dementia, we found that an increasing proportion of DHA in RBCs was related to a lower risk of AD and all-cause dementia. Of note, participants at the top quintile of RBC DHA had roughly half the risk of developing AD during follow-up compared to those at bottom quintile. We also detected a possible interaction between RBC DHA x APOE-e4 carriership, with a stronger inverse association between RBC DHA and risk of AD in e4 carriers—individuals at increased genetic risk of late-onset AD—than non-carriers. This suggests that carriers may benefit more from higher DHA levels than non-carriers [6].
Three of our findings are important. First, this study supports the hypothesis of a link between diet and brain health, since the most effective way to raise RBC DHA levels is to consume more preformed DHA. Thus, DHA, a fatty acid also known to have cardiovascular benefits [25], might also slow the progression of AD. Second, based on our estimations, changing from the lowest quintile (<3.8% of DHA in RBC membranes) to the top quintile (>6.1%) could translate into an estimated gain of 4.7 years free of AD. This was roughly half of the apparent benefit gained from not carrying an APOE-e4 allele. Given that estimated health-care payments in 2021 for all patients with AD or other dementias amount to $355 billion in US (not including caregiving by family members and other unpaid caregivers) [26], any cost-effective strategy for delaying the onset of AD is of utmost public health interest. Delaying AD by 5 years leads to 2.7 additional years of life, and 4.8 additional AD-free years for an individual who would have acquired AD, and is worth over $500,000 [27]. Third, after excluding e2/e4 participants (because of the known protective effects of the e2 allele), we observed an interaction DHA x APOE-e4 carriership on incident AD and all-cause dementia, with a trend towards a greater benefit of DHA in e4 carriers than in non-carriers. A plausible explanation for this finding is that APOE-e4 carriers might need more DHA to overcome their lower status of DHA (secondary to accelerated liver catabolism of DHA) coupled to impaired delivery of DHA to the brain [6]. This exploratory finding, which should be confirmed in more prospective studies with adequate statistical power, suggests that the APOE genotype modulates the associations between DHA and incident AD, and reinforces the need to target these particular individuals for supplementation, as expanded upon below.
Our study is in line with that of Tan et al., who reported cross-sectional associations with RBC DHA on cognitive performance and brain volume measurements (with higher DHA being associated with beneficial outcomes) in the same cohort as studied here [28]. Most interestingly, 15 years ago, similar findings were reported by Schaefer et al. in the parents of the individuals who were the focus of this present investigation (i.e., the Original Framingham Heart Study cohort). Schaefer et al. reported that participants in the top quartile of plasma phosphatidylcholine DHA experienced a significant, 47% reduction in the risk of developing all-cause dementia compared with those with lower levels [13]. Similar findings a generation apart in a similar genetic pool provide considerable confirmation of this DHA-dementia relationship.
Despite mounting evidence on the association between circulating DHA and preserved brain structure [9,10], blood-brain barrier integrity [29], and lower cerebral amyloidosis [30], several longitudinal studies on circulating DHA and incident AD/dementia failed to report statistically significant associations for DHA [11,12,17,18], while reporting significant inverse associations for DHA + EPA [12,15] or EPA alone [17,18]. In our study, using RBC EPA + DHA (i.e., the omega-3 index) or RBC EPA as the exposures of interest resulted in weaker and non-significant associations than for DHA alone. Future research is warranted to better delineate the extent to which EPA and/or DHA is the better marker of risk for dementia, and whether plasma concentrations vs. percent composition vs. RBC is the optimal sample type to analyze for omega-3 content when evaluating patients with respect to dementia.
In terms of clinical relevance, the lack of benefits in cognitive performance in randomized controlled trials involving DHA [31-35] urges to improve the design of future trials. Other study designs to elucidate causation (e.g., Mendelian Randomization) may also be valuable, though identifying a good quality genetic instrument for DHA may prove challenging [36,37]. Our results imply that certain people might benefit more from DHA-based interventions than others. This perspective is aligned with the 21st century shift towards "precision nutrition" and "personalized medicine." Specifically, two patient characteristics would be of interest. First, those with low DHA status, as suggested by results from the Multidomain Alzheimer Preventive Trial (MAPT), in which 3-year supplementation with 800 mg DHA + 225 mg EPA showed no significant effect on cognitive decline overall in older people with memory complaints [34], but benefits were observed in a subgroup of individuals with low omega-3 status at baseline [38]. This finding spawned the ongoing "low-omega (LO)-MAPT" trial (18-month intervention in older adults with omega-3 index < 4.83%; [39]), which will hopefully shed light on this issue. The second group that might benefit from DHA supplementation is individuals who are genetically at risk of AD (i.e., APOE-e4 carriers). In these people, subclinical structural and functional brain changes associated with AD take place years (even decades) before AD is present. There is increasing evidence for cognitive benefit from dietary DHA in cognitively healthy e4 carriers (consistent with our findings), but not in those with AD or mild cognitive impairment [6]. Therefore, there may be a window of opportunity to identify cognitive healthy e4 carriers and manage their associated elevated dementia risk with a dietary intervention (i.e., dietary DHA, but requiring doses close to 2 g/d [40]).
The strengths of this study are the inclusion of a large sample of older adults living in a community setting, with comprehensive cognitive assessments, continuous dementia surveillance, and collection of multiple health measures that can be included as potential confounders in statistical models. Furthermore, we used objective measurements of DHA and EPA from RBC, which reflect their long-term intake more accurately than dietary intake questionnaires. However, our study has several limitations. First, given its observational nature, it cannot address causality, and it is not possible to establish the directionality of associations. Second, the low number of e4 carriers resulted in a less precise effect estimates; therefore, our exploratory finding should be replicated in larger studies with greater statistical power. Third, we could not exclude the possibility that uncaptured environmental or other genetic factors may have influenced or caused the observed associations. Fourth, there is no information on whether a single measurement of RBC DHA is appropriate to estimate the risk of AD over long-term follow up when compared to repeated measurements. Finally, additional studies are needed to replicate these results in more diverse populations.

Conclusions

In conclusion, in a cohort of dementia-free participants from the Framingham Heart Study aged 65 years and older, we observed that those with a baseline RBC DHA proportion above 6.1% (top quintile) had nearly half the risk of developing AD (and all-cause dementia), and had an estimated 4.7 extra years of life free of AD compared to those with an RBC DHA below 3.8% (bottom quintile). In addition, we observed a trend for a stronger association in between RBC DHA and risk for dementia in e4 carriers than non-carriers, a finding that needs further research. Our results, which concur with a growing experimental research foundation, suggest that an increased DHA intake may be a safe and cost-effective strategy in preventing AD in specific populations.

VitaminDWiki - Omega-3 helps many health problems

371 Omega-3 items in category Omega-3 helps with: Autism (9 studies), Depression (29 studies), Cardiovascular (31 studies), Cognition (48 studies), Pregnancy (36 studies), Infant (24 studies), Obesity (13 studies), Mortality (5 studies), Breast Cancer (6 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), VIRUS (12 studies), etc

   See also - Overview: Omega-3 many benefits include helping vitamin D


VitaminDWiki - 48 studies in both categories Cognitive and Omega-3

This list is automatically updated


VitaminDWiki - Overview Alzheimer's-Cognition and Vitamin D contains


VitaminDWiki pages with ALZHEIMER in title (78 as of June 2022)

This list is automatically updated

Items found: 81
Title Modified
COVID increased seniors risk of Alzheimer's by 1.7X in the next year- Sept 2022 16 Sep, 2022
Alzheimer's disease 9X more likely in females with a poor Vitamin D Receptor – Sept 2022 27 Aug, 2022
Alzheimer's 9X more likely in women with a poor Vitamin D receptor – Sept 2022 11 Aug, 2022
Alzheimer’s delayed 4.7 years by high Omega-3 index (7.6 years if also have APOE-4) June - 2022 17 Jun, 2022
Alzheimer's disease 1.8 X higher risk if poor Vitamin D Receptor (if not take action) - May 2022 11 Apr, 2022
Alzheimer’s patients have less Magnesium – meta-analysis Jan 2022 08 Apr, 2022
Resveratrol fights Parkinson, Alzheimers, Diabetes, Cardiovascular, ALS, Stroke, etc.– Nov 2018 14 Mar, 2022
Overview Alzheimer's-Cognition and Vitamin D 09 Feb, 2022
Alzheimer's 3X higher risk in countries with high meat consumption - 2016 01 Feb, 2022
End of Alzheimer's video and transcript - Oct 2021 09 Nov, 2021
Mutated gene, OAS1, which lowers vitamin D in brain, increases Alzheimers and severe COVID-19 – Oct 2021 15 Oct, 2021
Omega-3 paused Alzheimer's decline - RCT Sept 2021 11 Sep, 2021
2X higher risk of Alzheimer’s if poor Vitamin D Receptor – Meta-analysis June 2021 25 Jun, 2021
The End of Alzheimer's - if custom adjust Vitamin D, B-12, Iron, Omega-3, etc. 14 Jun, 2021
Medicare kicks-back 6 percent of price of an administered drug to physicians, perhaps 6 billion dollars annually for Aduhelm (Alzheimer’s) drugs 13 Jun, 2021
Vitamin D influences inflammation and Alzheimer’s genes (in mice) – March 2021 09 Apr, 2021
Alzheimer’s Disease risk is 1.9 X higher if Vitamin D deficient- meta-analysis Feb 2020 06 Feb, 2020
Lower vitamin D in blood causes Alzheimer's Disease (Mendelian gene analysis) – Dec 2019 10 Dec, 2019
Alzheimer’s Disease risk is 1.3X higher if Vitamin D deficient – meta-analysis Nov 2019 16 Nov, 2019
Alzheimer’s cognitive decline is 3X faster if low vitamin D – May 2017 12 Jun, 2019
Alzheimer’s is associated with all 7 of the genes which restrict vitamin D from getting to tissues – Sept 2018 01 May, 2019
Resveratrol for Alzheimer's disease – Sept 2017 27 Apr, 2019
Omega-3 helped Alzheimer’s only if good level of B vitamins – RCT April 2019 10 Apr, 2019
Alzheimer’s (1.2X) and Parkenson’s (1.3X) more likely if poor Vitamin D Receptor – meta-analysis March 2019 23 Mar, 2019
8 genes associated with both Alzheimer’s and lowish Vitamin D – May 2019 23 Mar, 2019
African Americans are more likely than whites to develop Alzheimer’s (Vitamin D) 29 Jan, 2019
Standard Omega-3 not get past BB barrier in seniors at high risk of Alzheimer’s – Patrick hypothesis Oct 2018 25 Dec, 2018
APOE4 gene problems (Alzheimer’s) reduced by both Vitamin D and Omega-3 - Dec 2018 12 Dec, 2018
Alzheimer's risk increased 7 percent for every 4 ng decrease in Vitamin D– meta-analysis Nov 2018 27 Nov, 2018
Hypothesis: Low Vitamin D is a cause of Alzheimer’s Disease – 2014 23 Nov, 2018
Multiple Sclerosis, Alzheimer’s and Parkinson’s need more than 30 ng of Vitamin D – review Nov 2017 24 Sep, 2018
Alzheimer’s (apoE4) may require more than Omega-3 - May 2017 18 Sep, 2018
Alzheimer’s associated with low sun and low vitamin D – Sept 2018 18 Sep, 2018
Alzheimer’s Disease is associated with genes which restrict vitamin D – Aug 2015 18 Sep, 2018
Hypothesis: Omega-3 reduces Alzheimer’s directly and via the gut – Sept 2018 11 Sep, 2018
Alzheimer’s associated with Vitamin D and Vitamin D receptor – video and pdf – Aug 2018 02 Sep, 2018
The Startling Link Between Sugar and Alzheimer's 02 Jun, 2018
Alzheimer’s increase due to less sun or more meat 22 Apr, 2018
Why Alzheimer’s studies using Omega-3 have mixed results – quality, dose size, Omega-6, genes, etc. March 2018 18 Mar, 2018
Risk of Dementia and Alzheimer's reduced by higher levels of Vitamin D – meta-analysis Feb 2018 16 Feb, 2018
Alzheimer's disease – less risk if smarter, higher vitamin D, better genes or less coffee – Dec 2017 08 Dec, 2017
Alzheimer’s, Parkenson’s, and Multiple Sclerosis – vitamin D may prevent and treat – Oct 2017 07 Dec, 2017
Vitamin D and Multiple Sclerosis, Alzheimer's, Parkinson's ,Dementia, and ALS - review Nov 2017 23 Nov, 2017
Lymphatic system discovered in brain (what about Multiple Sclerosis, Alzheimer’s, Omega-3 and Vitamin D) – Oct 2017 07 Oct, 2017
Omega-3 found to treat Alzheimer’s and Parkinson’s in animals – Sept 2017 02 Oct, 2017
Alzheimer plaque possibly cleared by Vitamin D – Nov 2017 02 Aug, 2017
Alzheimer's disease most likely will need more than monotherapy such as vitamin D – May 2013 27 Apr, 2017
Severe Alzheimer's delayed by 1 year with vitamin D intervention – March 2014 05 Mar, 2017
Genes which reduce blood-level vitamin D increase the risk of Alzheimer’s disease – Dec 2016 18 Jan, 2017
Alzheimer’s and Vitamins D, B, C, E, as well as Omega-3, metals, etc. – June 2013 13 Oct, 2016
DDT 3.8 X more prevalent with Alzheimer disease (no mention that DDT decreases vitamin D) – Jan 2014 13 Oct, 2016
Parkinson's and Alzheimer's: associations with vitamin D receptor genes and race – meta-analysis July 2014 23 Sep, 2016
Decrease of Alzheimer’s biomarker halted by Resveratrol (perhaps due to vitamin D) – RCT Sept 2015 08 Aug, 2016
Cognition of Alzheimer’s patients improved by daily 4,000 IU of vitamin D – RCT Jan 2015 16 Apr, 2016
Poor Cognition and Alzheimer’s Disease both associated with low vitamin D – review May 2015 16 Apr, 2016
Alzheimer risk reduced by combination of memantine and vitamin D (patented) – Jan 2014 16 Apr, 2016
Alzheimer’s patients are genetically 70 percent more likely to be vitamin D in-efficient – Feb 2012 16 Apr, 2016
Alzheimer’s 4X less likely with high level of vitamin D – 2 studies April 2012 16 Apr, 2016
Vitamin D reduces Alzheimer’s disease in at least 11 ways – Jan 2013 13 Dec, 2015
Alzheimer's Disease more likely with low vitamin D – meta-analysis Oct 2012 13 Dec, 2015
Off Topic: Heat Shock Proteins (sauna etc) prevent clumping in Alzheimer’s – Oct 2015 24 Oct, 2015
Alzheimer’s Disease is associated with vitamin D and genes – Aug 2015 10 Sep, 2015
Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012 10 Sep, 2015
Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D gene – 2012 10 Sep, 2015
Alzheimer’s may be treated by vitamin D3 and curcumin – March 2012 01 Sep, 2015
Alzheimer’s disease 21 percent more likely if low vitamin D – meta-analysis Aug 2015 07 Aug, 2015
Alzheimer disease 5X less likely with nonmelanoma skin cancer (lots of vitamin D) – May 2013 01 Aug, 2015
5X fewer hip fractures from Parkinson – Alzheimer – Stroke with enough sun – June 2011 17 Jul, 2015
Gut, Alzheimer, autism, disease, fecal transplant, etc - Dr. Perlmutter, May 2015 18 May, 2015
Why vitamin D in Alzheimer's disease - a hypothesis – Jan 2014 16 Nov, 2014
Alzheimer’s disease – vitamin D looks promising – Annweiler Jan 2014 06 May, 2014
Brain (Alzheimer’s) worked better with Vitamin D intervention – meta-analysis July 2013 05 May, 2014
Hypothesis – Alzheimer’s Disease results of hormone imbalance (vitamin D etc.) – Jan 2014 15 Jan, 2014
Comparison of Alzheimer's Disease and Parkinson's Disease – Sept 2013 27 Dec, 2013
Vitamin D and MS, ALS, Autism, Alzheimer’s and other nervous system diseases – review Aug 2013 27 Dec, 2013
Alzheimer's disease 30 percent more likely in the 30 years after a low vitamin D test – July 2013 23 Jul, 2013
Alzheimer’s and Parkinson’s diseases associated with low vitamin D – meta-analysis June 2013 22 May, 2013
Alzheimer’s patients not on medication have very low levels of Vitamin D2 – Nov 2012 12 Nov, 2012
Alzheimer disease associated with 2.5 ng less vitamin D – meta-analysis Sept 2012 09 Oct, 2012
Link between diabetes and Alzheimers is probably low vitamin D 26 Sep, 2012
Alzheimer's probability decreased 77 percent with just 51 IU more vitamin D daily – April 2012 16 Sep, 2012

VitaminDWiki pages with DEMENTIA in title (41 as of June 2022)

This list is automatically updated

Items found: 44
Title Modified
Doggie dementia 6.5X more likely if not get exercise (probably low vitamin D) - Aug 2022 27 Aug, 2022
Dementia 2X more likely after ICU (suspect low Vitamin D) - Aug 2022 02 Aug, 2022
Calcitriol (activated Vitamin D) increases dementia (however, regular D decreases it) – June 2022 13 Jul, 2022
Dementia is associated with low vitamin D - several studies 15 Jun, 2022
Vitamin Supplementation and Dementia - Review May 2022 11 May, 2022
Lewy Body Dementia (Robin Williams) and low Vitamin D 11 May, 2022
Dementia 10X lower in a group who are outdoors a lot and eat unprocessed foods - March 2022 07 Apr, 2022
Mild cognitive impairment is 3X more likely to become dementia in one year if low vitamin D – March 2022 07 Apr, 2022
Dementia 1.7X higher risk if diabetic and low vitamin D - Jan 2022 14 Feb, 2022
Dementia 4.1 X high risk in those with low Vitamin D, Omega-3, etc.2 decades before (behind paywall) – Nov 2021 22 Nov, 2021
Dementia reduced 26 percent after pollution was reduced a decade earlier (probably higher Vitamin D) – Aug 2021 19 Aug, 2021
Cognitive Impairment and Dementia often associated with low Vitamin D – April 2020 08 Jan, 2021
The Evidence is strong: Air pollution seems to cause dementia (perhaps low Vitamin D) – May 2019 09 May, 2019
Vitamin or Mineral Supplements Don’t Prevent Dementia (only one Vitamin D trial, it used 400 IU) – Feb 2019 04 Feb, 2019
Treating herpes reduced incidence of senile dementia by 10 X (HSV1 reduces VDR by 8X) – 2018 17 Jan, 2019
Why dementia gets more severe in the winter – Jan 2019 14 Jan, 2019
Vitamin D and neurological diseases such as stroke, Vascular Dementia, PD, MS - July 2018 07 Dec, 2018
Osteoporosis in men increased their risk of Dementia by 1.3 (60,000 Germans) – July 2018 21 Aug, 2018
Dementia – clinical trial using 4,000 IU of Vitamin D– 2023 02 Aug, 2018
Dementia risk increased 2.4 X following TBI, even if had not lost consciousness – May 2018 12 May, 2018
Dementia less likely with increased levels of Magnesium etc. 18 Apr, 2018
5 Traumatic brain injuries resulted in 2.8 X increased risk of dementia – April 2018 11 Apr, 2018
Off Topic: Dementia risk reduced 90 percent if woman had been highly fit 40 years before 18 Mar, 2018
Risk of Dementia and Alzheimer's reduced by higher levels of Vitamin D – meta-analysis Feb 2018 16 Feb, 2018
Should you have a dementia advanced directive - Jan 2018 19 Jan, 2018
Dementia risk reduced 29 percent by just 10 hours of computer brain plasticity training – RCT Dec 2017 08 Dec, 2017
Vitamin D and Multiple Sclerosis, Alzheimer's, Parkinson's ,Dementia, and ALS - review Nov 2017 23 Nov, 2017
Heart Attack increased risk of vascular dementia by 1.35 X (both associated with low vitamin D) Oct 2017 15 Nov, 2017
Dementia risk factor is increased by 1.5 if low vitamin D – meta-analysis Jan 2017 15 Jan, 2017
Dementia 19X more likely if low vitamin D – Jan 2012 27 Oct, 2016
The "Surprising Link" Between Vitamin D Deficiency and Dementia (nope) - Oct 2015 04 Oct, 2016
The "Surprising Link" Between Vitamin D Deficiency and Dementia (not a surprise) - Oct 2015 04 Oct, 2016
Dementia risk significantly increased if have 4 chronic diseases – all associated with low vitamin D – Sept 2015 11 Dec, 2015
Vascular dementia (after strokes) 32X more likely in Hypertensives with low vitamin D – Oct 2015 01 Nov, 2015
Dementia surprisingly associated with low vitamin D (should not a surprise) – Aug 2014 03 Oct, 2015
Dementia 13X more likely in elderly with low vitamin D – May 2014 04 Sep, 2015
Dementia risk increases with latitude (less vitamin D) - Feb 2015 20 Feb, 2015
Chance of Dementia increased 3 percent for every 1 ng less of vitamin D – Feb 2015 04 Feb, 2015
The Single Vitamin That's a Double Whammy Against Both Depression and Dementia (Mercola) – Aug 2014 21 Aug, 2014
More depression associated with more dementia in seniors (vitamin D not mentioned) – July 2014 31 Jul, 2014
Age-adjusted dementia may be declining – NEJM Dec 2013 01 Jan, 2014
Dementia risk increases 60 percent if have low vitamin D – Nov 2012 16 Dec, 2013
Dementia associated with low vitamin D in two thirds of studies – systematic review May 2013 01 Aug, 2013
Vitamin D might might reduce dementia – Mar 2011 23 Jun, 2012


Created by admin. Last Modification: Saturday June 18, 2022 00:29:40 GMT-0000 by admin. (Version 10)

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17900 Omega-3 index and AD. Dem.jpg admin 17 Jun, 2022 23:19 38.65 Kb 48
17899 Alz delayed.jpg admin 17 Jun, 2022 23:18 32.94 Kb 62
17898 High DHA delays Alz by 4.7 years_CompressPdf.pdf PDF 2022 admin 17 Jun, 2022 23:17 322.45 Kb 17
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