So far no efficacious treatment has been available for the treatment of AD. Recent publications highlight the potential of life style and nutritional measures to reduce the prevalence of this disease.Several clinical and biomarkers have been described [1], and measurement of plasma pTau181 [2] was found to correlate with cortical tau protein deposition assessed by PET scan [3], which may provide an opportunity for diagnosing the diseaseand initiating therapeutic intervention at an early stage of neurodegeneration.  

According to the Lancet Commission on Dementia [4]12 risk factors for dementia should be considered, namely: less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, traumatic brain injury, and air pollution. It is the conviction of the author that stress, be it moderate or severe but long lasting, should be added to the list of factors that can be modified by timely intervention. Recent research highlights the pivotal role of nutrition, in particular the intake of flavonoids [5]. Furthermore autoimmune diseases [6-8], such as inflammatory bowel disease [9], were found to be associated with increased risk of AD.

The unifying mechanisms involved with many of these predisposing factors are immune disorder, chronic inflammation, oxidative stress and neuro-endocrine deregulation, probably inducing genetic and epigenetic alterations. Complementary treatments may possibly correct these alterations.

Cerebral blood supply can be improved by several phyto therapeutic agents. While serum lipid concentrations can favourably be influenced by the intake of fermented red rice [10],capillary blood supply is enhanced by the extract of Ginkgo biloba that exerts a anti-thrombotic action and improves brain cognitive function [11].

Meldonium acts as an inhibitor of acetyl-carnitine synthesis and reduces the transfer of fatty acids into the mitochondria. This promotes the compensatory glucose-pyruvate use in the aerobic metabolism of the Krebs cycle. Meldonium decreases fatty acid accumulation in the endothelial cells of the arteries, and enhances cerebral blood supply with resulting increased cellular metabolism [12,13].

Glucose metabolism in the cerebral neurones is exceptionally important,but is impaired in case of insulin resistance. The latter should always be detected in patients with dementia, and may related to the long-term use of statins [14].Conventional treatment uses Metformin, but this substance can be ketogenic, and its dose should be adapted depending on renal function. Metformin acts on the molecular pathway enhancing the adult neural precursor proliferation/self-renewal and differentiation, mainly by activating the AMPK pathway [15]. The extract of Momordica charantia (bitter melon) is non-toxic and highly efficient in restoring insulin sensitivity [16]. The triterpenoids of bitter melon induce activation of AMPK [17,18] with equal beneficial effect on the generation of neural precursor cells.Its effectiveness persists during long-term intake, and the substance is well tolerated.The efficiency of Momordica extract can be enhanced by combining it with alpha lipoic acid[19], thus improving neuronal function.

Sodium dichloroacetate is an inhibitor of mitochondrial pyruvate dehydrogenase kinase and boosts aerobic metabolism and the generation of adenosine triphosphate (ATP). Its efficacy has been proven for the treatment of brain dysfunction in patients with myalgic encephalomyelitis [20].Recent studies suggest this substance may alleviate metabolic impairment in the neurons of patients with AD [21] and stimulate angiogenesis [22].

Neuronal function is also enhanced by supplementingvitamins B9 (folic acid) and B12(methylcobalamine) which reduce homocysteine concentration [23], and prevent thinning of the cerebral cortex in persons with elevated serum homocysteine concentration. Increased metabolic energy production in the neurons will enhance signal transduction through the axons. This can be improved further by supporting the function of the Schwann cellsthrough the supplementary administration of phosphatidylcholine [24] which will be incorporated into the myelin sheath.

The pivotal importance of inflammation in the pathogenesis of dementia cannot be overemphasised[25,26]. Non-steroidal anti-inflammatory drugs (NSAIDs) may prevent AD, though the evidence from observational studies must be interpreted with restraint [27]. Anthocyanidins are a subclass of flavonoids with important health benefits [28] thanks to their potent anti-inflammatory and anti-oxidant capacities.Pine bark extract is a rich source of anthocyanidins [29].This extract was found to decelerate plaque development [30] and to attenuate amyloid-βand Tau misfolding [31], improving memory in experimental AD in miceas well as in humans [32]. Indeed, elevated nutritional flavonoid intake was related to an important decreased risk of developing AD [5].

Unhealthy lifestyle, inadequate nutrition with excess intake of ultra-processed food, insulin resistance, impaired arterialblood supply and hypertension, exposure to environmental toxins, and long-lasting stress all result in oxidative stress, which is considered an important issue in understanding the pathogenesis of AD [33,34].Hence,antioxidant treatment may help to prevent and to treat neurodegenerative diseases [35-37].Plant extracts with antioxidant properties are probably most appropriate for this purpose [38,39,5]. Astaxanthin,that is present in the biomass of the microscopic algae Haematococcus pluvialis, is a strong carotenoidantioxidant freeof toxicity. Based on its antioxidative, anti-inflammatory and anti-apoptotic properties, Astaxanthin can tackle neurodegeneration [40].Thanks to its antioxidative effect at the level of the mitochondria, the oxidoreductase Ubiquinol Q10does improve aerobic metabolism and energy generation of Krebs cycle. The neuroprotective potential related to phytochemicals [41] in the extract of Rhodiola rosea has been successfully applied in the therapeutic strategy of AD[42], improving learning and memory functions [43]. This phyto-adaptogen also reduces general anxiety and depression that are commonly associated with incipient dementia[44]. 

Similarly, edible medical mushroom extracts may be administered for the management of neuro-degenerative diseases [45,46] and depression [47]. The extract of Hericium erinaceus was proven particularly effective in this respect [48,49]. Poly-unsaturated omega-3 fatty acids, the long chain eicosapentaenoid acid (EPA) and docosahexaenoid acid (DHA) in particular, upregulate gene expression concerned with neurogenesis, neurotransmitters and connectivity, improving endothelial nitric oxide generation, enhancing brain acetylcholine levels, and protecting neurons from inflammation caused by cytokines and prostaglandins [50]. These fatty acids are abundant in fish oil, but krill oil may be preferable for of ecological reasons, and because EPA and DHA are present as phospholipids which enhances their cellular uptake [51].