Alzheimer’s Disease


The pharmacological treatment of Alzheimer’s disease (AD) is often limited and accompanied by serious drug side effects. (Source)

Failure of monotherapeutics

Neurodegenerative disease therapeutics has been, arguably, the field of greatest failure of biomedical therapeutics development. Patients with acute illnesses such as infectious diseases, or with other chronic illnesses, such as cardiovascular disease, osteoporosis, human immunodeficiency virus infection, and even cancer, have access to more effective therapeutic options than do patients with AD or other neurodegenerative diseases such as Lewy body dementia, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. In the case of Alzheimer’s disease, there is not a single therapeutic that exerts anything beyond a marginal, unsustained symptomatic effect, with little or no effect on disease progression. Furthermore, in the past decade alone, hundreds of clinical trials have been conducted for AD, at an aggregate cost of billions of dollars, without success. This has led some to question whether the approach taken to drug development for AD is an optimal one.

Therapeutic success for other chronic illnesses such as cardiovascular disease, cancer, and HIV, has been improved through the use of combination therapies [5]. In the case of AD and its predecessors, mild cognitive impairment (MCI) and subjective cognitive impairment (SCI), comprehensive combination therapies have not been explored. However, the past few decades of genetic and biochemical research have revealed an extensive network of molecular interactions involved in AD pathogenesis, suggesting that a network-based therapeutics approach, rather than a single target-based approach, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s disease.


5. Bredesen DE and John V. Next generation therapeutics for Alzheimer’s disease. EMBO Mol Med. 2013; 5:795-798. [PubMed]


Holistic approach


Systems biology and systems therapeutics of AD

The transgenic mouse studies suggest that APP signaling can be manipulated to inhibit AD pathophysiology. However, the mouse models feature mutations in APP or other familial AD-related genes such as presenilin-1, whereas the large majority of patients with AD suffer from sporadic AD, without an APP or PS1 mutation (although the majority do express the ε4 allele of ApoE). Given the many inputs to the APP signaling balance in humans (e.g., estrogen, netrin-1, Aβ, etc.), and the minimal success with each of many potentially therapeutic agents (e.g., estrogen, melatonin, exercise, vitamin D, curcumin, Ashwagandha, etc.), the pathobiology of AD dictates a system or program rather than a single targeted agent. Successes with other chronic illnesses such as cardiovascular disease, neoplasia, and HIV support the efficacy of multiple-component systems. My colleague and I have recently described such a system for AD [5]. The basic tenets for such a comprehensive therapeutic system are the following:

  1. Just as for other chronic illnesses such as atherosclerotic cardiovascular disease, the goal is not simply to normalize metabolic parameters, but rather to optimize them. As an example, a serum homocysteine level of 12 μmol/l is considered to be within normal limits, but is well documented to be suboptimal [27]. Similar arguments can be made for many other metabolic parameters.
  2. Based on the hypothesis that AD results from an imbalance in an extensive plasticity network, the therapy should address as many of the network components as possible, with the idea that a combination may create an effect that is more than the sum of the effects of many monotherapeutics [5].
  3. Just as for other chronic illnesses such as osteoporosis, cancer, and cardiovascular disease, the underlying network features a threshold effect, such that, once enough of the network components have been impacted, the pathogenetic process would be halted or reversed. Therefore, even though it is not expected that most patients will be able to follow every single step of the protocol, as long as enough steps are followed to exceed the threshold, that should be sufficient.
  4. The approach is personalized, based on the contributory laboratory values affecting the plasticity network; and is computationally intensive, since many physiological data points are analyzed, interdependent network-component status is assessed, and many interventions are prioritized to determine the therapeutic program.
  5. The program is iterative, so that there is continued optimization over time.
  6. For each network component, the goal is to address it in as physiological a way, and as far upstream, as possible.




Thus alternative and holistic therapeutic strategies are needed.

In order to determine a satisfactory course of remedial action, it is necessary to know Alzheimers’ etiology (causes). In Alzheimer’s disease, a peptide called amyloid beta forms aggregates (oligomers), which accumulate in the brain and form deposits known as amyloid plaques. (Source) Inflammation and oxidative damage are also associated with the progession of Alzheimer’s disease. (Source). Recent research at the Brown University in Rhode Island and elsewhere (Source), suggests that the development of Alzheimers is connected to lifestyle assaults, in particular to that which causes diabetes, the lack of insulin sensitivity. To read more, click here….

Screen Shot 2017-11-08 at 8.31.42 AM

Top: Electro-medicine and Alzheimer’s disease:

Non-invasive brain stimulation. Few studies have demonstrated that transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson’s disease, and stroke. tDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. AD’s neurobiological mechanisms comprise changes in neuronal activity and the cerebral blood flow (CBF) caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation via degenerated modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i) neuronal activity and (ii) human CBF, (iii) has synaptic and non-synaptic after-effects (iv), can modify neurotransmitters polarity-dependently, (v) and alter oscillatory brain activity and (vi) functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it could prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable us to identify its therapeutic validity in other types of demential disorders” .Front Psychiatry. 2012;3:48. doi: 10.3389/fpsyt.2012.00048. Epub 2012 May 15. Action mechanisms of transcranial direct current stimulation in Alzheimer’s disease and memory loss. Hansen N. Source Department of Neurophysiology, Ruhr University Bochum Bochum, Germany. (Source). There are 13 studies in pub med on tDCS and Alzheimier like conditions (source) and source a.  Clinical trial ongoing. For Israel research, see source. For technique modalities, source. This technique is also good for pain source and source b and source c

Happiness Medicine & Holistic Medicine Posts



Follow me on Twitter

Translate »
error: Content is protected !!