Alzheimer’s Disease

Lithium Deficiency and the Onset of Alzheimer’s Disease

By Frank M. Painter|September 18, 2025|Alzheimer's Disease|

Lithium Deficiency and the Onset of Alzheimer’s Disease

SOURCE: Nature 2025 (Aug 6) [EPUB]

Liviu Aron • Zhen Kai Ngian • Chenxi Qiu • Jaejoon Choi • Marianna Liang •
Derek M Drake • Sara E Hamplova • Ella K Lacey • Perle Roche • Monlan Yuan< • Saba S Hazaveh • Eunjung A Lee • David A Bennett • Bruce A Yankner

Department of Genetics,
Harvard Medical School,
Boston, MA, USA.

You may want to read this in-depth review of this study, created by PBS News.

The author interviewed the Harvard scientists, and this review is a testament to clarity and quality journalism, before you jump into reading this dense and complex study.

You will be glad that you did.

The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood. [1-5] Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration.

We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline.

These effects were mediated, at least in part, through activation of the kinase GSK3β. Single-nucleus RNA-seq showed that Li deficiency gives rise to transcriptome changes in multiple brain cell types that overlap with transcriptome changes in AD.

Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice.

These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.

From the Full-Text Article:

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Evidence for Brain Glucose Dysregulation in Alzheimer’s Disease

By Frank M. Painter|February 13, 2018|Alzheimer's Disease|

Evidence for Brain Glucose Dysregulation in Alzheimer’s Disease

The Chiro.Org Blog

SOURCE: Alzheimers Dement. 2017 (Oct 19) [Epub]

Yang An, Vijay R. Varma, Sudhir Varma, Ramon Casanova, Eric Dammer et al.

Laboratory of Behavioral Neuroscience,
National Institute on Aging (NIA),
National Institutes of Health (NIH),
Baltimore, MD, USA.

INTRODUCTION: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer’s disease (AD) pathogenesis.

METHODS: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose.

RESULTS: Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations.

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Brain Atrophy in Cognitively Impaired Elderly

By Frank M. Painter|July 29, 2015|Alzheimer's Disease, Supplementation|

Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-chain ω-3 Fatty Acids
and B Vitamin Status in a Randomized Controlled Trial

The Chiro.Org Blog

SOURCE: Am J Clin Nutr. 2015 (Jul); 102 (1): 215–221

Fredrik Jernerén, Amany K Elshorbagy, Abderrahim Oulhaj,
Stephen M Smith, Helga Refsum, and A David Smith

From the Oxford Project to Investigate Memory and Ageing (OPTIMA),
Department of Pharmacology,
University of Oxford, Oxford, United Kingdom;

This study provides clarity to earlier studies that found that B vitamins and/or Omega-3 fatty acids were found to slow brain loss in areas of the brain associated with Alzheimer’s disease.

In a 2010 study, Smith et al. [1] (in the Oxford Project to Investigate Memory and Ageing study) gave 271 individuals with mild cognitive impairment high-dose B vitamins for 2 years. Pre- and post-MRI studies were done, and they demonstrated that the B vitamin group experienced 30-percent slower rates of brain atrophy, on average, and in some cases patients experienced reductions as high as 53 percent.

In a 2012 study, Bowman et al. [2] (in the Oregon Brain Aging Study) reviewed blood nutrient levels in 104 dementia-free elders. They found two nutrient biomarker patterns (NBPs) that were associated with more favorable cognitive and MRI measures: one was high plasma levels of the vitamins B, C, D, and E, and the second NBP was high plasma marine omega-3 fatty acids. They also demonstrated that high trans fat blood levels were associated with less favorable cognitive function and less total cerebral brain volumes.

When this article was pre-released, the New York Times ran a banner headline titled:
4 Vitamins That Strengthen Older Brains. [3]

In a 2013 study, Douaud et al. [4] provided high-dose B-vitamin treatment to elderly subjects with increased dementia risk for 2 years. They found that B vitamins reduced brain shrinkage and reduced levels of plasma total homocysteine (tHcy). This is important because many cross-sectional and prospective studies have shown that high tHcy levels are associated with cognitive impairment, Alzheimer’s disease (AD), and vascular dementia.

The current study also helps explain why some trials that focused solely on the B vitamins or Omega-3s had mixed results. Apparently having high blood levels of BOTH the B vitamins AND Omega-3 fatty acids provides better results in preventing the deterioration of brain tissue in Alzheimer’s patients.

REFERENCES:

Homocysteine-lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial
PLoS One. 2010 (Sep 8); 5 (9): e12244
Nutrient Biomarker Patterns, Cognitive Function, and MRI Measures of Brain Aging
Neurology. 2012 (Jan 24); 78 (4): 241–249
4 Vitamins That Strengthen Older Brains
The New York Times ~ January 2, 2012
Preventing Alzheimer’s Disease-related Gray Matter Atrophy by B-vitamin Treatment
Proc Natl Acad Sci U S A. 2013 (Jun 4); 110 (23): 9523–9528

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Can Alzheimer’s Disease Be Prevented?

By Frank M. Painter|July 27, 2013|Alzheimer's Disease, Prevention|

Can Alzheimer’s Disease Be Prevented?

The Chiro.Org Blog

SOURCE: Medscape Medical News ~ June 24, 2013

Bret S. Stetka, MD

Reporting from The American Psychiatric Association’s 2013 Annual Meeting

Introduction

“Do we have any control over our brain health as we age?”, Dr. Gary Small asked the crowd, a packed room of psychiatrists attending his “Brain Health and Alzheimer’s Prevention” talk at the 2013 Annual Meeting of the American Psychiatric Association (APA) in San Francisco, California. [1]Nearly everyone raised their hands. “If the answer is yes,” he followed, “then what can we do to forestall the symptoms of Alzheimer’s disease (AD)?” For the next hour, conference-goers found out or, perhaps, given their line of work, brushed up.

Dr. Small is Professor of Psychiatry and Director of the UCLA Longevity Center at the Semel Institute for Neuroscience & Human Behavior. As session chair Dr. Brent Forester pointed out in his introduction, Small’s list of achievements is humbling: renowned clinician, cutting-edge researcher, author of over 400 scientific publications and 7 popular books, including his latest, The Alzheimer’s Prevention Program. His research has contributed to brain imaging methods capable of detecting AD years before symptoms are present; his healthy lifestyle and memory training programs are widely used throughout the United States. In 2002, Scientific American Magazine named Small one of the world’s top innovators in science and technology.

Up went an image of Madame Jeanne Calment, a French supercentenarian who lived to 122 years. “At 94, Calment sold her apartment to a businessman who agreed to pay her rent for the rest of her life. He died 10 years later,” said Small to the chuckling crowd. He was introducing the idea that certain lifestyles are associated with both longevity and brain health, a term encompassing our various neurologic faculties like memory, thinking, reasoning, mood, and stress responses. There are certain regions in the world — so-called “blue zones” — with abnormally high clusters of centenarians, most notably Sardinia, Italy; Loma Linda, California; and Okinawa, Japan. These regions share a number of characteristics thought to contribute to collective longevity and prolonged brain health on which Small would later expand: Namely, their inhabitants tend to be physically active, socially engaged, and eat a healthy diet high in omega-3 fats, just like the fish-heavy fare most likely enjoyed by Ms. Calment in the south of France.

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Alzheimer’s Disease

Lithium Deficiency and the Onset of Alzheimer’s Disease

Lithium Deficiency and the Onset of Alzheimer’s Disease

Evidence for Brain Glucose Dysregulation in Alzheimer’s Disease

Evidence for Brain Glucose Dysregulation in Alzheimer’s Disease

Brain Atrophy in Cognitively Impaired Elderly

Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-chain ω-3 Fatty Acids and B Vitamin Status in a Randomized Controlled Trial

Can Alzheimer’s Disease Be Prevented?

Can Alzheimer’s Disease Be Prevented?

Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-chain ω-3 Fatty Acids
and B Vitamin Status in a Randomized Controlled Trial