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Alzheimer’s, Cholesterol, and Genetics – How to Reduce Your Risk for Dementia

Alzheimer’s, Cholesterol, and Genetics – How to Reduce Your Risk for Dementia

It has been known for more than two decades that elevated cholesterol was associated with increased risk for Alzheimer’s Disease (AD).[1] It is also known that the ApoE gene produces a protein that transports fats, including cholesterol, into brain cells.

In the human population, there are three variants of the ApoE gene. Seven percent of the population has ApoE2, which confers increased risk for atherosclerosis; 79% has ApoE3, which confers no disease risk; and 14% of the population has the ApoE4 variant, which increases the risk for AD.

But, not everyone with either the ApoE4 gene or elevated cholesterol gets AD. Could there be an interaction between the higher concentrations of cholesterol and a specific ApoE gene variant that does increase the risk? The answer seems to be yes. Research has demonstrated that modulation in cholesterol alters the ApoE gene activity.[2] Further research has discovered a nexus between these two factors. A high-fat diet was demonstrated to increase insulin resistance and cognitive decline in all groups, whether ApoE4 or ApoE3. However, those with the ­ApoE4 gene had “exaggerated” deficits in the part of the brain specific to new learning and forming new memories in the hippocampus, but when those with the ­ApoE4 gene were placed on a low-fat diet for one month, all deficits reversed and learning and cognitive function returned to normal![3] The researchers concluded that those with two copies of the ­ApoE4 gene were particularly susceptible to neuronal and cognitive impairments due to insulin resistance caused by a high-fat diet.

Having demonstrated that low-fat diets result in improved cholesterol profiles and subsequent improvement in brain and cognitive function — especially in those with two copies of the ApoE4 gene, researchers examined whether cholesterol lowering medications could offer the same benefit. Data from long term clinical trials have demonstrated that some, but not all, cholesterol lowering medications conferred reduced risk of AD and better cognitive performance, especially in those with two copies of the at-risk ApoE4 gene. The greatest positive effect was seen with atorvastatin (P = .026) and the least with lovastatin (no significant difference found). Those individuals with two copies of the at-risk gene and who already had symptoms of AD, but received statin medication, had significantly better cognitive function over the course of a 10-year follow-up, compared with those who did not receive the statins (P < .01).[4]

Recently, researchers from Johns Hopkins University have discovered another brain protein that appears to be involved and works in concert with elevated b-amyloid to cause the cognitive and memory impairments of AD. The NPTX2 gene is one of the first genes to get activated when new memories are forming. If you are trying to remember what you are reading in this article, then normally NPTX2 would activate and produce the protein with the same name (NPTX2). This protein acts as an instigator and activator of synaptic signaling and neural circuit recruitment, critical in the formation of new memories. Without this protein, the neural circuits cannot effectively synchronize to form new memories. When this gene is turned down at the same time b-amyloid is building up in the brain, the neural circuits’ ability to adapt and organize is impaired, contributing to the cognitive and memory decline of AD. Individuals with high b-amyloid and high NPTX2 did not show cognitive changes of AD, and individuals with low NPTX2 and low b-amyloid also did not show impairment of cognition and memory. This study documented that both high b-amyloid and low NPTX2 were required for the negative outcomes. The good news is that the cause of suppressing NPTX2 is different than what causes elevations in b-amyloid.[5] This provides additional opportunities to make lifestyle changes to protect our brains and prevent dementia — even if one has the at-risk genes.

So, what turns on the NPTX2 gene? Activity of the neurons themselves![6] Staying mentally engaged and cognitively active — people who are lifelong learners — keep the neurons active and NPTX2 turned on, with reduced risk of AD. Additionally, externally firing the neurons with treatments such as electroconvulsive therapy has been documented to increase the expression of this gene.[7] These two findings makes it likely that any activity that increases the neuronal firing will activate the NPTX2 gene and may be one of the benefits of transcranial magnetic stimulation, which causes neuronal firing via magnetic waves rather than electrical pulses.

Not only does NPTX2 enhance learning, neural circuitry recruitment, synchronicity, and brain neural plasticity, it also modulates a receptor (AMPA) involved in non-programmed cell death. Therefore, while normal amounts of NPTX2 are neural protective, and low amounts increases the risk of dementia, significantly higher than normal activity of NPTX2 can trigger AMPA and instigate unscheduled cell death. This, unfortunately, appears to occur in persons with Parkinson’s disease and Lewy Body dementia, where NPTX2 is increased by more than 800% in the motor pathways.[8]

Another protein critical in maintaining brain health is repressor element 1-silencing transcription (REST) factor. REST functions within the cell like a conductor of an orchestra, directing various genes to sound out (express themselves) or be silent (turn off). As a result, REST is involved in determining how neurons develop, what function they fulfill, their connections and networking to other neurons, and, as expected, is highly active in childhood during the massive remodeling of brain development.

In the past, it was believed REST became inactive after a person reached adulthood. However, recent research has discovered REST is active in older brains and functions to protect the memory circuits (hippocampus) from damage due to hyperexcitation and plays a key role in protecting the brain from damage associated with aging. Reduced levels of REST are associated with loss of brain volume in the hippocampus (memory circuits) and increased cognitive impairment. In persons who have the toxic build up of protein associated with Alzheimer’s dementia (amyloid and tau), those with high REST activity did not demonstrate cognitive decline or progress to dementia, supporting the idea that REST is neural protective. The critical question: What affects the availability of REST? Chronic mental stress suppresses REST, contributing to accelerated aging and cognitive decline, whereas meditation, that reduced stress, is associated with increased levels of REST and subsequent brain health. [9]

With all of this in mind, genetics appears to account for about one-third of the risk of developing AD. What is the key then that contributes to developing AD, if it isn’t simply genetics? Strong evidence points to inflammation, which contributes to insulin resistance in the brain, that causes a cascade of events, resulting in the death of brain cells and the development of AD. Exercise, along with most of the other modifiable factors (sufficient sleep, anti-inflammatory diet, stress management, etc.), reduces inflammation and insulin resistance, keeps neurotrophins (proteins that act like fertilizer for the neurons), REST, NPTX2, and other protective factors turned on, thereby preventing the development of AD.

While aging is inevitable, dementia is not! We can make choices to protect our brains and prevent the development of late-life Alzheimer’s dementia. I recommend my new book, The Aging Brain: Proven Steps to Prevent Dementia and Sharpen Your Mind, which is an integrative examination of the various contributing factors to AD and outlines a comprehensive action plan to slow the aging process and keep our brain healthy.


[1] Jarvik GP, et al. Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: a case-control study. Neurology. 1995;45(6):1092–6.

[2] Petanceska SS, et al. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci. 2003;20(3):395–406.

[3] Johnson LA, Torres ER, Impey S, et al. Apolipoprotein E4 and insulin resistance interact to impair cognition and alter the epigenome and metabolome. Sci Rep. 2017;7:43701

[4] Geifman N, Brinton RD, Kennedy RE, et al. Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease. Alzheimers Res Ther. 2017;9:10.

[5] Xiao MF, Xu D, Craig MT, et al. NPTX2 and cognitive dysfunction in Alzheimer’s disease. eLife. 2017 March 23;6.

[6] Reti, IM, et al., Prominent Narp expression in projection pathways and terminal fields. J Neurochem. 2002 Aug;82(4):935-44.

[7] Reti, IM, Baraban JM, Sustained Increase in Narp Protein Expression Following Repeated Electroconvulsive Seizure, Neuropsychopharmacology (2000) 23, 439–443. doi:10.1016/S0893-133X(00)00120-2

[8] Moran, LB, et al., Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodies, Acta Neuropathol. 2008 April; 115(4): 471–478.

[9] Ashton N, Hye A, Leckey C et al. Plasma REST: A Novel Candidate Biomarker of Alzheimer’s Disease Is Modified by Psychological Intervention in an At-Risk Population. Transl Psychiatry. June 6, 2017; 7(6): e1148

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Testimony 54

I had a lot of pressure, as a pastor’s kid, to conform and be “good.” I was good at being “good.” I thought my life was going along well until it all started falling apart and I could not figure out why! In my search for “why is this happening to me, God?” I came across your book, “Could it be this Simple,” and God started revealing to me the many distortions I held about His character, His principles, and how He has designed His universe to operate. I remember thinking, “Wow, I have had this all backwards.” I was happy and angry all at the same time. Happy to have the light of truth break through the darkness, revealing a wonderful, beautiful way of understanding God and His plan for His children, and angry, because I felt deceived and cheated by the church, my family, and myself!

My heart thrills when I listen to your bible study lessons. Literally I have gone from death to life. It is a journey I look forward to every day, as God reveals areas this distortion affects. Praise GOD! I will ever be grateful to God for this ministry and your cooperation with the Spirit!

Karen S., Portal, AZ, USA

 

Testimony 1

Thank you! I love listening to the Come And Reason Ministries Bible study classes and am using some of your notes to get the lessons together that I will be teaching. You always have such good quotes and Bible texts and pull things together to make good sense.

T. C., IN, USA

 

Testimony 49

I came into the church at 21, but that is as far as it went. I was so confused about what love is. I couldn’t find it in the bible, because I am not a person that can read between the lines. I have no logic. I have read many, many books; trying to figure out the crux of the matter. They were helpful, but something was still missing. I have become very frustrated to the point of crying out to God, “Where can I go?”  I needed some basics.

I found two books, written by Timothy Jennings, MD, to be very helpful. God showed me that I had lived my whole life in fear. I didn’t even see it. Now, I do. God is so good.  I discovered the “The Remedy”  Dr. Jennings new book, “The God-Shaped Heart!” Oh, I was so excited, I purchased them right away.

I can get rid of most of my books, because “The Remedy” brings the Love of God out so clearly, even I can’t miss it. Now, I want to sit and read my Bible. Wow, what a revelation! It is just simply Awesome! I am so grateful to Jehovah Almighty for hearing my prayer for more understanding! I am so encouraged!

Jackie S.

 

Testimony 48

I just want to tell you how blessed I have been reading “The Remedy!” It has become a daily part of my devotional relationship with God. In it I have found a God of love and a God that loves me! The bible has come alive for me! It is the first time that I can say that I have felt hope fill my heart as I have read God’s word. This is good news I can share! Thank you, Dr Jennings! Thank you for your heart for others. I can’t put into words how this has set me free! It has strengthened my trust and love for God.

Jason H.

 

Testimony 7

Ok, so last night I listened to “The Law of Liberty” and “How to Achieve Victory: Freedom, Truth and Spirtual Warfare.” These are both MY ABSOLUTE FAVORITES so far! The logic is just soooooo beautiful. I had to re-listen to them a couple of times. I just want to EXPLODE! (<< we assume with joy and happiness)

N. B., Canada

 

Testimony 50

After coming into contact with Come And Reason Ministries, I can finally say that many of my unanswered questions have fallen into place. I discovered that my view of God’s Law was “imposed laws and rules” with “imposed punishments” and that this was the major culprit of my many unanswered questions. Thanks be to God for using you and those around you to help us who have struggled with this “infection” of thought. I have now rejected the “imposed law” concept to fully embrace “Design Law”… to look thru “Design Law,” instead of “imposed law,” is a relief.

Viliami L., Australia

 

Testimony 17

The blessings of clarity and understanding you and your class inspire me to take from the word of God have impressed upon me so greatly the true, loving character of our Creator. I have found amazing freedom and joy through building a stronger, more intentional relationship with Him. What is new is that this is now a relationship built on love, reverence and respect rather than fear and obligation, and as such my eyes have been slammed OPEN as I am continually impressed by the manifestations of God’s true character in His provisions for fallen man.

T.E.H., Salt Lake City, UT, USA

 

Testimony 16

Your seminars are still inspiring and changing our lives and we continue to share the principles we have learned from you. Your ministry has changed our lives!

E.W.

 

Testimony 43

Two years ago I stumbled upon your book, “Could It Be This Simple,” and then found “The God-Shaped Brain” videos on YouTube, your bible study class, and the ‘Come And Reason’ mobile app. I shared your book with a friend and after nine months of showing love, patience, and kindness this person has been changed by the love of God, too. The same love that healed me, I now express to other women in tangible ways, such as to a Baptist woman with high anxiety and childhood trauma. She was extremely happy and relieved when I shared about the so-called “judgment of God” and burning in hell. She had no desire to serve a God that was so harsh. I have repeated the phrase dozens of times to her. “What we believe has power over us, but we have power over what we believe…”

This message that you are sharing has changed my life. I will continue to serve other women and bring this message of God’s healing love to their lives by sharing your books, YouTube videos, and The Remedy Bible app. Keep up the good work. Don’t be discouraged. God is doing a mighty work in and through this ministry!

Jill L., Midwest, USA

 

Testimony 18

The Healing the Mind DVD set tarted me on a journey that has changed my relationship with our loving God more significantly than any other study, and brought me to your book and Bible study podcasts, which I now listen to daily, thanks to the availability of archived content on your site and on iTunes.

Anonymous

 

Testimony 51

I Love This Ministry!!!!!!! I see first hand how this message is desperately needed, how erroneous beliefs about God and His Character negatively affect humanity at every level. I thank God for your ministry, as I was searching on my own and was discovering some of your same beliefs and was blown away when I found your ministry. I know you hear it all the time, but it is truly life changing. May God continue to reveal His Will to you and Bless you!

Eric S., Sanford, FL, USA

 

Testimony 57

You have helped make sense of thirty two years of confusion. The material you freely provide reorganized so much of my life into such a beautiful pattern that has always been hinted at from within, but misguided with my training and what I was experiencing externally. My filipno parents, who were converted from Catholicism to SDA, were sincere and did their best to raise me the right way and I have deep respect for them. However, being immigrants and not understanding the language made for a difficult transition as I was growing up, which also applied to my spiritual growth as I learned the patterns of religion. I have been listening to as many bible study classes and reading blog posts as my time in a work truck will allow, searching for the practical applications of where spirituality and reality meet, and I thank you for helping me find that. You have helped me reach a point in which I can truly say that I love God, that I believe He loves me, and, like David, I delight in His law. God bless.

Emmanuel V., Calgary, AB Canada

Testimony 24

I wanted to thank you very much for presenting your understanding of God. I’ve always been troubled by this question: Why did Jesus have to die? Since my conversion I understood that The Father & Jesus are one, I did not have issues with that. But was there not any other way to save us than for Jesus to die? I guess I actually had a question about God – if He is so wise, how come He did not find another way? I did not see the real ‘beauty’  in the cross. Only when you explained the picture in the medical context, Jesus providing medicine for my selfishness, have I started to finally ‘see the light’. Thank you so much. Your seminar, “Healing the Mind,” are absolutely marvelous & have shared them with my family and many other people, including colleagues at work. Thanks, thanks, thanks. May God bless you abundantly in your ministry.

M. W., Australia

 

Testimony 71

When I was 9 years old, I remember setting at our devotional table with a hunger and thirst for God that wanted more, deeper, BETTER. I can remember literally crying and pounding on the table, “I know these teachers didn’t mean to give us error. They taught what THEY had been TAUGHT, but didn’t ANYBODY READ THE BOOK?!?!?” It mattered to me then. It mattered to me as a teenager. It matters now as I teach bible classes. It didn’t have to be so hard as I watched so many give up and lay God’s great plan and gift of salvation aside as being “impossible.” Then, a friend sent me a link to Come And Reason’s website. I grew excited. YES! FINALLY! Then another friend told me to stay away, saying her son had just broken up with a girl because she was involved with Come And Reason and that “Tim Jennings preaches a false gospel.” But, AFTER many years of developing an authentic and, dare I say FUN relationship with Jesus, through the Holy Spirit I see this message has been around a LONG time, since the apostle Paul, Ellen White, Graham Maxwell, Ray Foucher, and yourself (though I admit, you’ve made me back up, rewind and replay the clips, and get out my well-worn Bible on a few things.) I’m so thankful I have found LIGHT during these DARK days. I am not alone.

Vicki DiNitto

Testimony 22

I have found your Bible study class lectures to be very inspiring and useful as I prepare to teach class every other week. I subscribe to the podcast and download your notes on the weeks I teach. The audio and notes are such a great help in preparing. My own understanding of God’s character has grown as I teach the class. Commendations on the thought-provoking and well-prepared material Come and Reason provides. Personally, I get excited by the tie you make between the spiritual and mental/physical domains.

A.A. Corrales, NM, USA