The diagnosis of Alzheimer’s disease (AD) has challenged neurologists for many years. It’s difficult to determine if someone will develop AD in the future, if the actual cognitive deficit is due to AD or to other cause of dementia and it’s also difficult to predict the pace or speed of disease progression.

It is already known that Alzheimer’s pathological brain alterations (amyloid plaques and Tau-tangles) start long time before the appearance of clinical symptoms. We also know that lifestyle interventions are the only effective treatment to fight cognitive decline, especially when initiated in early stages of disease. That’s why, a test which could predict when the process starts and the rhythm of progression would be a useful tool in the clinical practice.

Many tests are nowadays available (see Diagnosis section for more information), but they are expensive and difficult to be used in the day by day clinic. They usually require brain image techniques that are either expensive and time consuming or invasive medical procedure like lumbar puncture – which is not free of adverse effects. 

Two new AD-tests have been developed within the last year and hope to finally bring ease and precision to the diagnosis of AD.

Published in Neurology in August 2019, a study presents a blood test that was able to measure the level of Aβ42/Aβ40 with high correspondence with amyloid PET status (brain image test). It showed that plasma Aβ42/Aβ40, especially when combined with age and ApoE4 status (see Genetics section for further information), accurately diagnoses brain amyloidosis and can be used to screen this pathological alteration in individuals with normal cognitive function, i.e., before presenting symptoms. It also showed that individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Thus, the test could be used to screen individuals likely to present brain amyloid deposit and hence, at risk for AD. 

In another study published in Lancet Neurology in May 2020, the authors developed and validated an ultrasensitive blood immunoassay for p-tau181. Tau phosphorylated at threonine 181 (p-tau181) level has been already measured in is cerebral spinal fluid (CSF) and is a highly specific biomarker for Alzheimer’s disease pathology. With this study, the authors showed that blood p-tau181 levels can predict tau and amyloid β pathological alterations and differentiate AD from other neurodegenerative disorders with high accuracy. Additionally, it predicts cognitive decline and hippocampal atrophy over a period of 1 year, making it suitable as a marker of disease progression.

Both tests have the advantage to be done in a blood sample, and were able to predict the risk of developing cognitive decline and its progression. They represent simple, practical and scalable tests for the diagnosis of AD. They are not yet available in the market, but have the potential to be incorporated into clinical practice as a rapid screening test to rule out AD and to guide therapy in patients with dementia. 

Considering the relevance of lifestyle measures for AD treatment and prevention, these tests provide security and certainty of when to start or intensify actions to control cognitive impairment. They can be also used to easily screen individuals at risk to future prevention trials, to promote lifestyle intervention and to improve our knowledge about this challenging disease.


Two  new tests for Alzheimer’s disease that determine highly specific biomarker substances in the blood, have been developed. These fast, precise and inexpensive tests may have important clinical applications: as a screening tool in the primary care setting; to monitor the disease progression; to differentiate AD patients from patients with other neurodegenerative disorders; and as a way of ensuring that subjects enrolled in clinical trials indeed have Alzheimer’s disease and that the treatments they are testing are effective. They will certainly become an important tool to ensure an accurate and early diagnosis and to motivate doctors and patients to implement lifestyle changes in order to prevent cognitive deterioration. KsD will keep its readers informed about the availability of these or other tests (please register today for our newsfeed).


  1. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422-433. doi:10.1016/S1474-4422(20)30071-5.
  2. Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647-e1659. doi:10.1212/WNL.0000000000008081
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Lithium is probably best known as a treatment for bipolar disorder but a very small dose of this element has been recently studied to prevent and slow the progress of AD. However, effective doses can sometimes cause negative side effects. 

Using animal models, scientists from McGill University (Canada) are now suggesting a novel microdose formulation of lithium could not only slow the progression of AD, but also potentially improve cognition at the early stages of decline. They tested a therapeutic agent called NP03, an encapsulated oral lithium formulation that can bypass degradation by acids in the gastrointestinal tract, resulting in high central nervous system uptake. This means significantly lower doses can be administered compared to conventional lithium.

The first study was published in 2017 and established the efficacy of the new microdose lithium formulation in the early or preclinical stages of AD by ß-Amyloid (Aß) deposition and restoring hippocampal neurogenesis. 

Microdoses of lithium at concentrations hundreds of times lower than applied in the clinic for mood disorders were administered at early amyloid pathology stages in the Alzheimer’s-like transgenic rat. Remarkably positive results of this study stimulated the researches to continue working and testing the new formulation on a more advanced pathology.

The new study explores the effects of the microdose formulation of lithium (NP03) on a slightly more advanced stage of AD, when amyloid protein plaques have begun forming and symptomatic signs of cognitive decline are already present. The results impressively demonstrated that NP03 reduced levels of amyloid plaques, reversed memory deficits, and lowered neuroinflammatory markers in the rodent model.

These results point to the potential neuroprotective benefits from sustained lithium microdoses and offer hope for AD treatment. However, it is important to note this particular microdose formulation is still yet to be tested in human subjects with AD, so much more work is necessary before it can be deployed as a clinical treatment.

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Although known to be essential for all animals with nervous system, the main cellular function of sleep is still unknown. Prolonged sleep deprivation can be lethal, and sleep disturbances are associated with various deficiencies in brain performance. 

Far from being relaxed when we’re sleeping, our brains are very active and uses a lot of energy. Most of the energy is spent on important “housekeeping work” such as: cleaning up, consolidating memories, getting rid of data it doesn’t need and cleaning out physical waste products, including beta-Amyloid deposits.

The mechanisms underlying solute clearance from the brain’s extracellular space have puzzled neurologists for centuries, once the central nervous system (CNS) is the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent studies have led to the discovery of the glymphatic system, a glial-dependent perivascular network with a lymphatic-like function in the brain.

The glymphatic pathway is a highly-organized fluid transport system where cerebrospinal fluid (CSF) and interstitial fluid (ISF) continuously interchange. In its initial segments, CSF from the subarachnoid space flows into the brain through perivascular spaces of the large arteries and is driven into the brain parenchyma through the perivascular spaces of penetrating arteries, also known as Virchow-Robins spaces. This flow across the brain parenchyma is facilitated from the water channels aquaporin 4 (AQP4), a protein which is densely expressed by glial cells. While flowing, the CSF mixes with the ISF. In the interstitium, the mixed fluid disperses via a polarized net fluid movement directed towards the venous perivascular space (fig1).

Potential factors affecting glymphatic pathways include respiratory cycle, arterial pulsations, changes in vasomotor tone, postural changes and sleep. This last factor is significantly important in cleaning waste product: the clearance of amyloid beta (Aß) during sleep is twice as fast as during awake periods.

Besides cleaning, the brain also needs sleep to replenish itself. During REM-stage and dreaming the brain works on fixing any damage suffered during the daytime: restores the metabolic stores, trims unneeded synapses, reinforces specific connections and overall becomes more energy efficient. It also works repairing damaged DNA inside neurons, increases chromosome dynamics and performs nuclear maintenance. These changes in chromatin dynamics have been shown to regulate key nuclear processes, including epigenetic functions.


The glymphatic system is a recent described mechanism that our brain uses to eliminate physical waste products, like amyloid beta (Aß). This system works mainly during sleep, specially during deep stages of sleep. This may help to explain the biological need for sleep across all species and reinforces the importance of a good night of sleep.

Sleep well and allow yourself to experience a proper brain “detox”, helping to prevent AD.


    1. Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease [published correction appears in Nat Rev Neurol. 2016 Apr;12(4):248]. Nat Rev Neurol. 2015;11(8):457–470. doi:10.1038/nrneurol.2015.119
    2. Zada, D., Bronshtein, I., Lerer-Goldshtein, T. et al. Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons. Nat Commun 10, 895 (2019) doi:10.1038/s41467-019-08806-w
    3. Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016–1024. doi:10.1016/S1474-4422(18)30318-1
    4. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner’s Guide. Neurochem Res. 2015;40(12):2583–2599. doi:10.1007/s11064-015-1581-6
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Lanabecestat is a potent inhibitor of Amyloid beta (Aβ) formation – the main component of amyloid plaques. Aβ is formed through cleavage of amyloid precursor protein (APP) by proteases known as secretases (β and γ). The Beta-site-APP-cleaving enzyme 1 (BACE1) cleaves APP at the β-secretase site, after which APP is cleaved by γ secretase to generate Aβ peptides. Lanabecestat inhibits BACE1 and was able to reduce levels of Aβ1-40 and Aβ1-42 in the brain, cerebrospinal fluid (CSF), and plasma in several animal models, as well as in human CSF and plasma. Besides that, Lanabecestat is brain permeable meaning that an adequate amount of this substance is able to reach the brain after oral intake.

Taking these facts into account, two clinical trials were designed to test if the oral administration of Lanabecestat would be effective in two different groups of patients: patients with mild cognitive impairment (the AMARANTH study) and patients with mild AD (the DAYBREAK-ALZ study). The main question in both studies was: can Lanabecestat slow the progression of cognitive deterioration?

Unfortunately, both studies had to be earlier terminated because no benefits were found in the groups using the substance compared with the group taking placebo, only side effects were noted.

The substance was able to reduce Aβ levels in CSF and was associated to a greater reduction in Aβ plaques density compared to placebo. But no positive clinical effect was shown.

Even though Lanabecestat was generally well tolerated, psychiatric adverse events were numerically greater in treatment groups compared with placebo group and were consistent with dose dependence. Lanabecestat exposure was also associated with hair color changes and weight loss. 

Full text:


In two new, randomized clinical trials, Lanabecestat (a potent Aβ inhibitor) did not slow cognitive or functional decline of AD compared with placebo. One more hope of treatment has failed. It appears unlikely that current BACE inhibitors will be an effective disease modifying treatment for symptomatic AD but future studies are still needed to determine if reduction in Aβ production can provide meaningful clinical benefit in earlier stages of the disease continuum or in other high-risk populations. 

 PREVENTION is still the best solution!

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This descriptive documentation of the Arte TV channel shows very clearly the connections between an unbalanced diet, the resulting micronutrient deficiencies and the effects on the brain. Various experiments have shown that mice that grow up with a deficiency of omega-3 fatty acids have deficits in the formation of their neurons and are much more anxious.

A particularly striking example showed an experiment with field hamsters. Here a simple vitamin B3 deficiency was sufficient to trigger aggressive behaviour during mating in over 80% of females. In the further course of the experiment, these females even ate their offspring directly after birth. After the vitamin B3 deficiency had been remedied, the females showed normal behaviour again, despite continued unbalanced diet  (thus the vitamin B3 factor could be clearly identified as the trigger).

In humans, long-term observations and studies showed similar results. Already in the uterus, the nutrition of the mother decides about the brain development and the emotional development of the fetus and newborn.

Mothers who eat “junk food” with a low omega-3 fatty acid concentration and high sugar content give birth to children that tend to act more aggressive. If this form of nutrition is continued in childhood, aggressive  behaviour, anxiety and attention disorders are pre-programmed. If there is a lack of omega-3 fatty acids, the function of the brain is disturbed, the communication between neurons and the neurogenesis are impaired.

The second cardinal error of Western nutrition is the flooding of highly processed foods with cheap refined sugars. Experiments have shown that this hidden sugar poisoning may show higher addiction effects  than cocaine. The consequences are insulin resistance, diabetes and dementia.

Of course, this form of unbalanced nutrition also has an effect on the intestines and the gut microbiota (and their genetic diversity, the microbiome), which have a significant influence on the health of our body and mind. Concrete examples show that the density of nutrients in food influences the way we   make decisions and solve daily problems. But we do not want to reveal too much here, watch for yourself:


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Unfortunately this excellent video don’t provide English subtitles, a more scientific alternative about the MIND diet in English can be found here:


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As far as mental and brain health is concerned, nutrition seems to be a major component of prevention, particularly with regard to dementia.  An alteration towards the Mediterranean diet or even better the MIND diet  increases our chances to remember the names of our grandchildren in the future and to actively participate in life. Just leave the “industrial garbage” on the shelf, even if it is sometimes difficult.

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The association between cognitive function and oral health has been well documented so far by some observational studies. On the one hand it has been reported that periodontal disease and tooth loss are associated with increased risk of dementia. On the other hand, improved memory after dental intervention has also  been observed. 

Those findings started the discussion about what would come first: Does initial cognitive decline lead to poor oral hygiene and dental loss, followed by poor nutrition, including decreased intake of vitamins, which would precipitate dementia? Or does periodontal disease increase concentrations of circulating inflammatory markers that might be involved in the pathogenesis of dementia?

Recently, this relationship has become clearer, with the characterization of Amyloid β (Aβ) as an antimicrobial peptide. Chronic periodontitis and infection with Porphyromonas gingivalis – a keystone pathogen in the development of chronic periodontitis – are significant risk factors for developing Aβ-plaques, dementia and AD. 

In a study published in Science Advances (1), a multinational team of investigators found that the presence of oral P gingivalis infection in mice resulted in brain infiltration by the bacteria, what was followed by increased production of Aβ, the component of amyloid plaques implicated in AD. They also found that AD brains showed a greater immunoreactivity to gingipains – a virulence factor produced by P gingivalis – than brains of non-AD control groups . Moreover, DNA from P gingivalis was found in the cerebral spinal fluid (CSF) of living AD patients and in postmortem studies of AD patients.

These findings offer evidence that brain infection with P gingivalis is not a result of poor dental care following the onset of dementia or a consequence of late-stage disease, but an early event that can explain the pathology found in middle aged individuals before cognitive decline. 

It supports the concept that Aβ is an antimicrobial peptide and reinforces the importance of maintaining a healthy microbiome to prevent AD.

Once the oral cavity is infected, P gingivalis may access the brain via a number of pathways including: 1) infection of monocytes followed by brain recruitment, 2) direct infection and damage to endothelial cells protecting the blood-brain barrier, and/or 3) infection and spreading through cranial nerves [e.g., olfactory or trigeminal] to the brain. 

After entering the brain, it modulates inflammatory innate and adaptive immune responses and activates the Aβ inflammatory cascade (see section causes for further information) with production of Aβ-plaques

Treating chronic periodontitis and P gingivalis infection with antibiotics or using a gingipain inhibitor could reduce the inflammatory response and brake Aβ-plaques formation. But the whole problem would reappear in case of a new episode of P gingivalis infection. 


The most important factor here is to keep a strong and healthy oral microbiome, which can prevent dysbiosis and assure the balance of oral cavity immune system. Who would have thought that a clean toothbrush and a proper oral hygiene (without too much fluoride) helps to stay mentally fit?


Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.

Yamamoto T, Kondo K, Hirai H, et al. Association between self-reported dental health status and onset of dementia: a 4-year prospective cohort study of older Japanese adults from the Aichi Gerontological Evaluation Study (AGES) Project. Psychosom Med 2012; April 74 (3): 241-8

Wu B, Fillenbaum GG, Plassman BL, Guo L. Association Between Oral Health and Cognitive Status: A Systematic Review [published correction appears in J Am Geriatr Soc. 2016 Aug;64(8):1752]. J Am Geriatr Soc. 2016;64(4):739–751.

Harding A, Robinson S, Crean S, Singhrao SK. Can better management of periodontal disease delay the onset and progression of Alzheimer’s disease? J Alzheimers Dis. 2017; 58 (2):337-348

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Several million patients in Germany are treated with statins. In 2004, the consumption of lipid-lowering drugs throughout Germany amounted to around 856 million defined daily doses (DDD). In 2011 the amount increased to: 1.718 million DDD.

With the target  to lower cholesterol levels, this doubtful strategy is still being mistakenly promoted to reduce heart disease risk. As a side effect, doctors and patients are accepting a possible cognitive decline.

These are the results of a study published in 2018 in the journal Frontiers in Neurology, which looked into the relationship between cholesterol and cognitive function [1]. While cholesterol is still largely vilified, and statin use still heavily promoted, the study found that having lower levels of low-density lipoprotein (LDL) cholesterol is linked to a higher risk of dementia.

High LDL Cholesterol: a Protective Factor Against Cognitive Decline

The study involved data from nearly 4,000 residents aged 50 years or over in an urban community in China. A high level of LDL cholesterol was found to be inversely associated with dementia in the study participants, even after controlling for other factors that might increase risk, including demographic characteristics, health behavior, mood assessment and medical history.

What’s more, the researchers noted, “There was a significantly higher proportion of participants with low levels of total cholesterol (TC) and [LDL] cholesterol in the dementia group than in groups without dementia.” The association was so strong that they concluded a high level of LDL cholesterol may be considered as a “potential protective factor against cognitive decline.”

This may come as a surprise for those who have been told that cholesterol is more of a burden than an asset, but other studies have also found cholesterol to be protective to the brain. For instance, cholesterol levels in the high-normal range were associated with better cognitive performance in people aged 65 years and older.

Those researchers concluded, “Low cholesterol may serve as a clinical indicator of risk for cognitive impairment in the elderly.”

An earlier U.S. study of more than 4,300 Medicare recipients aged 65 and over also revealed that higher levels of total cholesterol were associated with a decreased risk of Alzheimer’s disease, even after adjusting for cardiovascular risk factors and other related variables [2].

Other studies have found higher HDL cholesterol to be associated with better cognitive function, with researchers suggesting, “Further exploration of the protective effect of HDL-C [HDL cholesterol] on cognitive function in aging is warranted through follow-up, longitudinal studies.”

Why Higher Cholesterol Levels May Be Good for Your Brain

The brain contains up to 30 percent cholesterol, which is an essential component of neurons and of great importance to develop and maintain neuronal plasticity and function. Cholesterol is critical for synapse formation, i.e., the connections between the neurons, which allow you to think, learn new things and form memories.

Beyond this, it’s been suggested that high cholesterol could be an indicator of overall good nutritional status and health, whereas low cholesterol has been linked to a higher risk of mortality and is often seen alongside malnutrition and chronic diseases, including cancer.

The Frontiers in Neurology study authors [1] also suggest that, as a major component of the brain, decreasing cholesterol levels could be associated with cerebral atrophy, “a typical anatomic sign of dementia,” and other factors more directly related to your brain health. They continued:

“Another speculation is that high LDL-C could reduce neurons’ impairments or facilitate compensatory repair of injured neurons. The inhibitions of dendrite outgrowth and synaptogenesis, and the acceleration of neurodegeneration have been observed when neurons was a short of cellular cholesterol or cholesterol supply.

Besides, cholesterol plays an important role in the synthesis, transportation and metabolism of steroid hormones as well as lipid-soluble vitamins, both of which have an impact on synaptic integrity and neurotransmission.”

Therefore it is wise to be careful before taking statins!

Aside from an increased risk of dementia, statins deplete your body of Coenzyme Q10 (CoQ10), which accounts for many of their devastating results.

CoQ10 is used for energy production by every cell in your body. Its reduced form, ubiquinol, is a critical component of cellular respiration and production of adenosine triphosphate (ATP). ATP is a coenzyme used as an energy carrier in every cell of your body. The depletion of CoQ10 caused by statins can actually increase your risk of acute heart failure.

While this can be somewhat offset by taking a Coenzyme Q10 supplement, statins still come with a risk of other serious side effects, including:

  • Diabetes, Cancer, Cataracts, Musculoskeletal disorders, including myalgia, muscle weakness, muscle cramps, rhabdomyolysis and autoimmune muscle disease and depression.

Statins also inhibit the synthesis of vitamin K2, which can make your heart health worse instead of better, and reduce ketone production. Ketones are crucial nutrients to feed your mitochondria especially in the brain and are important regulators of metabolic health and longevity.


  • Having lower levels of low-density lipoprotein (LDL) cholesterol is linked to a higher risk of dementia, according to a study of nearly 4,000 people aged 50 and over
  • A high level of LDL cholesterol was found to be inversely associated with dementia in the study participants, even after controlling for other factors that might increase risk, including demographic characteristics, lifestyle, mood factors and medical history
  • The association is so strong, that a high level of LDL cholesterol may be considered as a “potential protective factor against cognitive decline”
  • The human brain contains up to 30 percent cholesterol, which is an essential component of neurons and necessary to develop and maintain neuronal plasticity and function
In the end, a nutrition scheme rich on healthy fats and low refined sugars is a promising strategy against dementia. The use of statins to lower cholesterol may end in a fast cognitive decline.

Statistik: Arzneimittelverbrauch von lipidsenkenden Mitteln* in Deutschland in den Jahren 2003 bis 2011 (in Millionen DDD**) | Statista
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[1] Zhou, F. et al. (2018) ‘High low-density lipoprotein cholesterol inversely relates to dementia in community-dwelling older adults: The Shanghai aging study’, Frontiers in Neurology, 9(NOV), pp. 1–8. doi: 10.3389/fneur.2018.00952.

[2] Reitz, C., Tang, M. X., Luchsinger, J., & Mayeux, R. (2004). Relation of plasma lipids to Alzheimer disease and vascular dementia. Archives of neurology, 61(5), 705–714. doi:10.1001/archneur.61.5.705

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