Alzheimer’s Reversing Cognitive Decline
Tina Beaudoin, ND
This year’s annual Institute for Functional Medicine (IFM) Conference presented some exciting research and positive clinical outcomes being achieved in the field of Alzheimer’s and cognitive decline. Integrative clinicians specializing in this field are reversing cognitive decline in early and moderate Alzheimer’s disease by identifying and addressing the underlying physiological imbalances.
For many decades, neuronal damage was believed to be irreparable. Dr. Peter Eriksson published the first study that “demonstrated that cell genesis occurs in the human brains and that the human brain retains the potential for self-renewal throughout life.” Research has expanded since this landmark study and integrative clinicians are working diligently to understand the multitude of factors that contribute to Alzheimer’s and most importantly, how to repair the damage.
In searching for solutions, the neurotrophic factor Brain Derived Nerve Growth Factor/BDNF is one of the key proteins in brain plasticity and offers many insights in brain health and cognitive decline. BDNF enhances neurogenesis, neuronal differentiation, and synaptogenesis, modulates appetite, enhances telomerase activity, supports development and maintenance of CNS function, enhances long-term potentiation in the hippocampus, and inhibits injury related apoptosis. Lower gene expression of BDNF is found in patients with Alzheimer’s, Parkinson’s, depression and obsessive-compulsive disorder.
There is a wide array of foundational integrative principles that have been found to up-regulate BDNF expression. Physical exercise and increasing caloric expenditure exhibits powerful epigenetic effects on upregulating BDNF expression. The Cardiovascular Health Study found that “higher energy output, from a variety of physical activity types, was associated with larger grey matter volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.” Regular physical activity (aerobic, resistance training, walking, etc.) not only leads to a 50% risk reduction of AD, it also benefits those patients with AD who benefitted with increased grey matter volume. Statistics can be a powerful motivator to get your sedentary patients to embrace a regular exercise routine.
It is not surprising with the decades of research on the gut-brain connection that a healthy GI tract is vitally important in brain health. Chronic intestinal inflammation alters hippocampal neurogenesis (impacting learning, memory and mood) and leads to significant behavioral changes, including cognitive impairment and depression. Zhang et al found significantly elevated levels of endotoxin LPS/lipopolysaccharides in patients with AD. Healing the digestive tract is essential in almost all chronic conditions and especially important in patients with Alzheimer’s and cognitive impairment. Research in animal models has also shown that prebiotics (with FOS) and probiotics positively impact expression of hippocampal BDNF after just five weeks. In patients with AD, Akbari et al found that 12 weeks supplementation with probiotics showed a significant improvement in the MMSE score (P <0.001) and several metabolic markers (hsCRP, insulin resistance, beta cell function and serum triglycerides).
Dr. Dale Bredesen, MD of the Easton Laboratories for Neurodegenerative Disease Research, UCLA and the Founding President of the Buck Institute is spearheading amazing research and clinical outcomes in AD. He has categorized AD into three major subtypes (and also combinations of these three subtypes) and notes that most patients do not fit into just one subtype but rather may have contributing factors from multiple subtypes.
Leading integrative experts in the field postulate that Alzheimer’s disease is actually a protective response to three types of major insults: inflammation, trophic withdrawal or toxin exposure. Inflammation could result from NFkB activation, from infectious agents or sterile triggers such as AGE-modified proteins. Trophic withdrawal could be secondary to decreases in nerve growth factor, human growth factor, insulin sensitivity, estradiol, testosterone, vitamin D and so forth. In terms of toxic exposure, the list is expansive and heavy metals and biotoxins are common culprits. Dr. Bredesen reports that most symptomatic individuals have at least 10-25 contributing factors. Dr. Bredesen stressed that clinicians must investigate what is triggering the brain to produce “protective” amyloid plaques and must not attempt to reduce the amyloid until they identify and remove the cause(s).
Three Major Subtypes of Alzheimer’s Disease
Type 1: Inflammatory (“Hot”)
- Increase in hsCRP and/or other inflammatory markers (Il-6, IL-8, TNFa, etc.)
- Reduction in albumin/globulin ratio
- Increase in M1/M2 macrophage ratio with reduction in MFI
- ApoE4 important risk factor
- Typically amnestic presentation
- Hippocampal atrophy is common
- Identify and address cause/s of inflammation such as leaky gut, AGEs, diet and poor oral hygiene
Type 2: Atrophic (“Cold”)
- Tend to be older than Type 1
- Typically amnesic but patients often deny problem
- Reductions in trophic hormones (e.g., estradiol, progesterone, testosterone, vitamin D, pregnenolone, thyroid, NGF, BDNF)
- ApoE4 is a risk factor
- Rapid reductions in support are most concerning (e.g., oophorectomy at <41yo without HRT), consistent with depR mismatch
- Optimizing support may be complicated by receptor response, HRT controversy, trophic factor delivery (intranasal vs. peptides vs. indirect, etc.)
Type 3: Toxic (“Vile”)
- >65 yo at age of onset, often ApoE4 negative
- Negative family history (or at increased age)
- HPA dysfunction
- Low triglycerides or zinc, depression
- Difficulties with math, organization or word finding
- Exposure to toxins/toxicants (e.g., mercury, mycotoxins, CIRS-related such as Lyme, MARCoNS, surgical implants, etc.)
- Stress precipitation or exacerbation
- “Atypical Alzheimer’s”, often with frontal effects and imaging
- Most difficult to treat successfully
- Second most common type
- High C4a (>2800), TGF-beta-1 (>2380), low MSH (<35)
Reframing of our understanding of AD and gaining a macroscopic view of potential contributing factors is essential to achieving clinical successes with patients. This very brief look into the changing field of AD only modestly touches on the amazing breakthroughs taking place. The therapeutics are diverse and include specialized light therapies, sound therapies, nutrition, targeted exercises to influence specific regions of the brain, supplements, graduated mental exercise programs, genetic support and so forth.
If you’d like to further explore specializing in this field, I highly recommend purchasing the recordings of the 2017 IFM Annual Conference and attending their Reversing Cognitive Decline Advanced Clinical Training Module and register for Dr. Bredesen’s intensive training programs. With the growing incidence of AD and neurodegenerative disease, the demand for integrative clinicians specializing in this field will only continue to soar.
 Eriksson et al. Neurogenesis in the adult human hippocampus. 1988. Nature Medicine 4, 1313 – 1317.
 Reyes-Izquierdo T. et al. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. Br J Nutr. 2013 Aug 28;110(3):420-5.
 Cyrus A. R., et al. Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study. J Alzheimers Dis. 2016; 52(2): 719–729.
 Zonis, S. et al. Chronic instestinal Inflammation alters hippocampal neurogenesis. J Neuroinflammation. 2015 Apr 3;12:65.
 Zhang et al. Circulating endotoxin and systemic immune activation in sporadic Amyotrophic Lateral Sclerosis (sALS). J Neuroimmunol. 2009 Jan 3; 206(1-2): 121–124.
 Savignac HM et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int. 2013 Dec;63(8):756-64.
 Akbari et al. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci. 2016; 8: 256.