Category Archives: Dementia

Is Rapamycin the Holy Grail of Anti-Aging Medicine?

MRI of brain

Rapamycin may prevent chronic age-related diseases like Alzheimer’s Disease. From P.D. Mangan who interviewed Alan S. Greeen, M.D., prescriber and user of the drug himself:

For many informed observers of anti-aging science and practice, rapamycin appears to be one of the most promising anti-aging treatments currently available. Originally (and still) used as an immunosuppressant for transplant patients, it’s been found to increase lifespan in lab animals.

Side effects of rapamycin are a problem, but it’s since been found that a transient (3-month) treatment with rapamycin can extend life expectancy up to 60%. More studies are needed to determine the dosing regimen with maximal efficacy and minimal side effects. Intermittent dosing at once every 5 days also extends lifespan in mice, and this “demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans. ” Note also that this dosing regimen wasn’t started until the mice were quite old, at 20 months, and it still extended lifespan.

The principal mechanism of action of rapamycin is the inhibition of the cellular nutrient sensor and growth regulator mTOR. In elderly humans, weekly dosing of an mTOR inhibitor (not rapamycin) increased immune function as measured by response to a flu vaccine.

Given all of this, rapamycin as it relates to the slowing or reversal of aging, is still an experimental drug. However, we will be waiting a long time, perhaps forever, for the FDA to approve rapamycin for anti-aging, and since it’s a generic drug, there’s little incentive for drug companies to pursue clinical trials. Meanwhile, many people have begun to realize that they could be dead before this treatment becomes recognized – again, if ever.

Source: Rapamycin Anti-Aging Medicine: An Update with Alan S. Green, M.D. – Rogue Health and Fitness

Mangan’s site is a trove of anti-aging strategies.

Steve Parker, MD.

Steve Parker MD, Advanced Mediterranean Diet

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Transcranial Electromagnetic Treatment in Alzheimer’s Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging 

A) A MemorEMTM head device being worn by a subject. B) Position of the eight electromagnetic emitters embedded between the device’s two-layered head cap. Emitters collectively provide global forebrain TEMT via rapid sequential emitter activation.

This is from the cited journal article. I hope this is considered fair use rather than copyright infringement.

This is the most creative therapeutic approach to Alzheimer’s Disease I’ve seen in a while. It may even be preventative. I have no idea whether it will pan out in the long run. I’m always skeptical.

Click for a Scientific American article that discusses a different experimental protocol and probably different device.

Abstract

Background: Small aggregates (oligomers) of the toxic proteins amyloid-β (Aβ) and phospho-tau (p-tau) are essential contributors to Alzheimer’s disease (AD). In mouse models for AD or human AD brain extracts, Transcranial Electromagnetic Treatment (TEMT) disaggregates both Aβ and p-tau oligomers, and induces brain mitochondrial enhancement. These apparent “disease-modifying” actions of TEMT both prevent and reverse memory impairment in AD transgenic mice.

Objective: To evaluate the safety and initial clinical efficacy of TEMT against AD, a comprehensive open-label clinical trial was performed.

Methods: Eight mild/moderate AD patients were treated with TEMT in-home by their caregivers for 2 months utilizing a unique head device. TEMT was given for two 1-hour periods each day, with subjects primarily evaluated at baseline, end-of-treatment, and 2 weeks following treatment completion.

Results: No deleterious behavioral effects, discomfort, or physiologic changes resulted from 2 months of TEMT, as well as no evidence of tumor or microhemorrhage induction. TEMT induced clinically important and statistically significant improvements in ADAS-cog, as well as in the Rey AVLT. TEMT also produced increases in cerebrospinal fluid (CSF) levels of soluble Aβ1-40 and Aβ1-42, cognition-related changes in CSF oligomeric Aβ, a decreased CSF p-tau/Aβ1-42 ratio, and reduced levels of oligomeric Aβ in plasma. Pre- versus post-treatment FDG-PET brain scans revealed stable cerebral glucose utilization, with several subjects exhibiting enhanced glucose utilization. Evaluation of diffusion tensor imaging (fractional anisotropy) scans in individual subjects provided support for TEMT-induced increases in functional connectivity within the cognitively-important cingulate cortex/cingulum.

Conclusion: TEMT administration to AD subjects appears to be safe, while providing cognitive enhancement, changes to CSF/blood AD markers, and evidence of stable/enhanced brain connectivity.

Source: A Clinical Trial of Transcranial Electromagnetic Treatment in Alzheimer’s Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging – IOS Press

Steve Parker, M.D.

PS: I notice that several of the study authors are based in my area of operations, south-central Arizona.

PPS: The Mediterranean diet for years has been linked to lower risk of dementia.

Steve Parker MD, Advanced Mediterranean Diet

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If Gut Bacteria Cause Alzheimer’s Dementia, What If You Alter Those Bacteria?

The short answer? We don’t know the answer to either of those questions.

Low-carb salad

The gut bacteria (aka microbiome) seem to be able to decrease or increase inflammation that could cause or exacerbate Alzheimer’s dementia. The  microbiome’s effect on inflammation depends on the species of bacteria present, and the amount of those bacteria. At least one study found that Alzheimer’s patients have a greater abundance of the pro-inflammatory species and less of the anti-inflammatory species, compared to other folks.

Researchers with Wake Forest School of Medicine tried to find answers to the questions in the title of this post. (Click for full text.) They studied 17 experimental subjects, average age 64, who had mild cognitive impairment (11) or “cogni/subjective memory complaints” (6). God bless them for submitting to three spinal taps apiece. The experimental diets were 1) Mediterranean-Ketogenic (under 20 g carb/day), or 2) Low-fat American Heart Association diet (under 40 g fat/day). Participants were on each diet for six weeks.

The investigators didn’t find anything useful for those of us trying today to avoid Alzheimer’s or prevent the progression of mild cognitive impairment to dementia. Their bottom line is, “The data suggest that specific gut microbial signatures may depict [characterize] the mild cognitive impairment and that the modified Mediterranean-ketogenic diet can modulate the gut microbiome and metabolites in association with improved Alzheimer’s disease biomarkers in cerebrospinal fluid.”

So we won’t know for several more years, if ever, whether intentional modification of diet will “improve” our gut microbiomes, leading to lower risk of dementia.

What we have known for many year, however, is that the traditional Mediterranean diet is linked to lower risk of Alzhiemer’s dementia.

For more details, see Science Daily:

In a small pilot study, the researchers identified several distinct gut microbiome signatures — the chemicals produced by bacteria — in study participants with mild cognitive impairment (MCI) but not in their counterparts with normal cognition, and found that these bacterial signatures correlated with higher levels of markers of Alzheimer’s disease in the cerebrospinal fluid of the participants with MCI.

Through cross-group dietary intervention, the study also showed that a modified Mediterranean-ketogenic diet produced changes in the gut microbiome and its metabolites that correlated with reduced levels of Alzheimer’s markers in the members of both study groups.

Source: Diet’s effect on gut bacteria could play role in reducing Alzheimer’s risk — ScienceDaily

Steve Parker, M.D.

Steve Parker MD, Advanced Mediterranean Diet

Two diets in one book, including the Ketogenic Mediterranean Diet

Click the pic to purchase the world’s first practical ketogenic Mediterranean diet at Amazon.com

 

Association of Intensive vs Standard Blood Pressure Control With Brain Small Vessel Ischemic Disease

Not good enough

Aiming for systolic blood pressure of 120 or less (instead of 140) may reduce the risk of age-related brain impairment. A recent study suggests the mechanism is better brain blood flow.

The 2017 guidelines from the American College of Cardiology recommend a BP treatment goal of under 130/80.

Ischemia means poor or no blood flow.

Small vessel ischemic disease (SVID in the brain) is something I see so often on CT scans of 70-year-olds that I usually ignore it. Mind you, I’m a hospitalist and usually looking for acute major strokes, brain tumors, and bleeding on CT scans. SVID is a chronic disease and it’s often difficult to say how long a specific lesion has been present and whether it’s causing symptoms. Ischemia in the brain is linked to impaired cognitive functioning and dementia. On the other hand, some brain ischemic lesions don’t seem to cause any detectable impairment.

From JAMA Network:

Question:  Is intensive blood pressure treatment associated with less progression of small vessel ischemic disease, as reflected by cerebral white matter lesion volume?

Findings:  In this substudy of a randomized clinical trial of 449 hypertensive patients with longitudinal brain magnetic resonance imaging, intensive blood pressure management to a target of less than 120 mm Hg, vs less than 140 mm Hg, was associated with a smaller increase in white matter lesion volume (0.92 cm3 vs 1.45 cm3).

Meaning:  More intensive blood pressure management was associated with less progression of cerebral small vessel ischemic disease, although the difference was small.

Source: Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions | Dementia and Cognitive Impairment | JAMA | JAMA Network

Steve Parker, M.D.

PS: The Mediterranean diet also reduces dementia and cognitive impairment.

Steve Parker MD, Advanced Mediterranean Diet

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Mediterranean Diet Helps Preserve Brain Function in Type 2 Diabetes

MRI scan of brain

From Practice Update:

CONCLUSIONS

Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.

Source: The Mediterranean Diet and 2-Year Change in Cognitive Function by Status of Type 2 Diabetes and Glycemic Control

Steve Parker, M.D.

PS: What else preserves brain function? The Mediterranean diet, for one.

Steve Parker MD, Advanced Mediterranean Diet

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Targeting Mouth Bacteria May Prevent Alzheimer’s Dementia

My only file foto of teeth

Several respected researchers think that Alzheimer’s dementia may primarily be an infectious disease, particularly related to gum bacteria.

From MedScape:

LOS ANGELES — As more disappointing results emerge from anti-amyloid drug trials in Alzheimer’s disease (AD), there is growing interest in novel treatment approaches for this condition.

One such approach is based on the hypothesis that Porphyromonas gingivalis (Pg), the bacteria involved in periodontal disease, may cause AD. The biopharmaceutical company Cortexyme Inc is testing this theory with an investigational agent COR388, which targets gingipains, the toxic proteases released by Pg.  Early results show the drug is well tolerated and promising in terms of biomarker findings. Organizers hope that a phase 2/3 trial of the treatment now under way will provide definitive efficacy results.

Source: Gum Disease Bacteria a Novel Treatment Target for Alzheimer’s?

Steve Parker, M.D.

PS: Did you know the Mediterranean diet reduces the risk of dementia?

Steve Parker MD, Advanced Mediterranean Diet

Click the pic to purchase at Amazon.com

Mediterranean Diet Improves Brain Function in Type 2 Diabetes

I don’t know if the study at hand is valid or not; I’m skeptical. The abstract is poorly written. The study population was Boston Puerto Ricans only, so may not apply to other ethnic groups. I’m not paying $35 to get access to the full article. Diabetes Self-Management has coverage that will be more palatable than the abstract below.

OBJECTIVE To determine associations of a Mediterranean diet score (MeDS) with 2-year change in cognitive function by type 2 diabetes and glycemic control status and contrast it against other diet quality scores.

RESEARCH DESIGN AND METHODS We used data from the longitudinal Boston Puerto Rican Health Study (n = 913; 42.6% with type 2 diabetes at 2 years). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7% [53 mmol/mol]) versus controlled. Two-year change in glycemic control was defined as stable/improved versus poor/declined. We defined MeDS, Healthy Eating Index, Alternate Healthy Eating Index, and Dietary Approaches to Stop Hypertension scores. Adjusted mixed linear models assessed 2-year change in global cognitive function z score, executive and memory function, and nine individual cognitive tests.

RESULTS Higher MeDS, but no other diet quality score, was associated with higher 2-year change in global cognitive function in adults with type 2 diabetes (β ± SE = 0.027 ± 0.011; P = 0.016) but not without (P = 0.80). Similar results were noted for Mini-Mental State Examination, word recognition, digit span, and clock drawing tests. Results remained consistent for individuals under glycemic control at baseline (0.062 ± 0.020; P = 0.004) and stable/improved over 2 years (0.053 ± 0.019; P = 0.007), but not for uncontrolled or poor/declined glycemic control. All diet quality scores were associated with higher 2-year memory function in adults without type 2 diabetes.

CONCLUSIONS Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.

Source: The Mediterranean Diet and 2-Year Change in Cognitive Function by Status of Type 2 Diabetes and Glycemic Control | Diabetes Care

Steve Parker, M.D.

Steve Parker MD, Advanced Mediterranean Diet

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