Vascular & Mixed Dementia


Vascular dementia, as its name suggests, is caused by poor blood flow, produced by a single, localized stroke, or series of strokes.

It is the second most common dementia, accounting for perhaps 17% of dementias. It also co-occurs with Alzheimer's in 25-45% of cases. Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.

Risk factors

In general, unsurprisingly, vascular dementia has the same risk factors as cerebrovascular disease.

A study1 of 173 people from the Scottish Mental Survey of 1932 who have developed dementia has found that, compared to matched controls, those with vascular dementia were 40% more likely to have low IQ scores when they were children than the people who did not develop dementia. Because this was not true for those with Alzheimer's disease, it suggests that low childhood IQ may act as a risk factor for vascular dementia through vascular risks rather than the "cognitive reserve" theory.


The exciting thing about vascular dementia is that it is far more preventable than other forms of dementia. As with risk, as a general rule, the same things that help you protect you from heart attacks and stroke will help protect you from vascular dementia. This means diet, and it means exercise.

A four-year study2 involving 749 older adults has found that the top one-third of participants who exerted the most energy in moderate activities such as walking were significantly less likely to develop vascular dementia than those people in the bottom one-third of the group.


Apart from normal medical treatment for cerebrovascular problems, there are a couple of interesting Chinese studies that have looked specifically at vascular dementia.

The herb gastrodine has been used in China for centuries to treat disorders such as dizziness, headache and even ischemic stroke. A 12-week, randomized, double-blind trial3 involving 120 stroke patients who were diagnosed with mild to moderate vascular dementia has found that  gastrodine and Duxil® (a drug used to treat stroke patients in China) produced similar overall levels of cognitive improvement -- although more patients showed 'much improvement' with gastrodine (23% vs 14%).

A Chinese pilot study4 involving 25 patients with mild to moderate vascular dementia found that ginseng compound significantly improved their average memory function after 12 weeks, but more research (larger samples, placebo-controls) is needed before this finding can be confirmed. Five years on I have still not seen such a study.


  1. McGurn, B., Deary, I.J. & Starr, J.M. 2008. Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia. Neurology, first published on June 25, 2008 as doi: doi:10.1212/01.wnl.0000319692.20283.10
  2. Ravaglia, G. et al. 2007. Physical activity and dementia risk in the elderly. Findings from a prospective Italian study. Neurology, published online ahead of print December 19.
  3. Tian, J.Z. et al. 2003. A double-blind, randomized controlled clinical trial of compound of Gastrodine in treatment of mild and moderate vascular dementia in Beijing, China. Presented at the American Heart Association's Second Asia Pacific Scientific Forum in Honolulu on June 10.
  4. Tian, J.Z. et al. 2003. Presented at the American Stroke Association's 28th International Stroke Conference on February 14 in Phoenix. Press release


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Review ranks safety, effectiveness of Alzheimer's drugs

  • A review of the safety and effectiveness of the four drugs approved for Alzheimer's treatment found that donepezil was the most effective, but also the most likely to produce side effects.
  • A small study found that combining a specific care management program with memantine multiplied the drug’s ability to improve daily function by about 7.5 times.

I rarely report on drugs, but because I do have a number of early reports on the four drugs approved for use with Alzheimer’s, I wanted to provide this update.

The four drugs are donepezil, rivastigmine, galantamine and memantine. This review is said to be the first to rank their comparative safety and effectiveness. It used evidence from 142 clinical trials published between 1996 and 2015. The number of patients in each study ranged from 13 to 2,045, and the review evaluated a total of 33,889 patients.

Donepezil was the most effective medication for Alzheimer's dementia across all effectiveness outcomes, including cognition, behavior and overall health, according to the study. It was also the only cognitive enhancer that produced effects that could be observed clinically, not merely statistically.

However, patients who took donepezil were more likely to experience side effects including nausea, vomiting and diarrhea than those who received a placebo.

Previous research found that these drugs don’t improve cognition or function in people with MCI, and these patients experience significantly more nausea, diarrhea, vomiting and headaches.

Memantine plus care program dramatically better at reducing Alzheimer's symptoms than drug alone

A small study found that combining a specific care management program with memantine multiplied the drug’s ability to improve daily function by about 7.5 times.

The Comprehensive, Individualized, Person-Centered Management program (CI-PCM) includes caregiver training, residence assessment, therapeutic home visits, and caregiver support groups.

In the 28-week, blinded, randomized controlled trial, 10 patient-caregiver groups enrolled in the CI-PCM were compared against 10 pairs receiving standard community care. All patients were taking memantine. Participants were assessed at the end of the trial using a recognized tool called Functional Assessment Staging (FAST), which measures losses in the ability of a person to independently carry out daily activities, such as dressing, bathing and toileting.

Caregiver training included "memory coaching" that teaches patients how to accomplish skills they lost.

The findings were presented July 16 at the Alzheimer's Association International Conference 2017 in London.


Tricco, A. C., Ashoor, H. M., Soobiah, C., Rios, P., Veroniki, A. A., Hamid, J. S., … Straus, S. E. (2018). Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer’s Disease: Systematic Review and Network Metaanalysis. Journal of the American Geriatrics Society, 66(1), 170–178.



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Older news items (pre-2010) brought over from the old website

Immunization with AB42 does not prevent dementia despite clearing associated brain plaques

Disappointingly, analysis of 80 Alzheimer's patients who had been involved in trialing immunisation against amyloid-β in September 2000, has found that, despite a lower level of amyloid-β plaques, there was no improved survival or increased time to severe dementia in those who were immunised.

Holmes, C. et al. 2008. Long-term effects of AB42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372 (9634), 216-223.

Vaccine prevents Alzheimer's

A vaccine has successfully prevented the development of amyloid plaques and tau tangles in the brains of genetically engineered mice. The vaccinated mice also demonstrated normal learning skills and functioning memory. There were no major side-effects. Human trials are still a few years off.

Frazer, M.E. et al. 2008. Reduced Pathology and Improved Behavioral Performance in Alzheimer's Disease Mice Vaccinated With HSV Amplicons Expressing Amyloid-β and Interleukin-4. Molecular Therapy, 16, 845-853.

Alzheimer's vaccine clears plaque but doesn't improve memory

A two-year canine study has revealed that although a promising vaccine being tested for Alzheimer's disease clears beta-amyloid plaques from the brain, it doesn’t seem to help restore lost learning and memory abilities. Autopsies showed that although plaques had been cleared from multiple brain regions, damaged neurons remained. The findings suggest that simply treating beta-amyloid plaques may have only limited clinical benefit if started after there is significant plaque growth, and a combination of vaccination with other therapies aimed at repairing damaged neurons may be best.

Head, E. et al. 2008. A Two-Year Study with Fibrillar β-Amyloid (Aβ) Immunization in Aged Canines: Effects on Cognitive Function and Brain Aβ. Journal of Neuroscience, 28, 3555-3566.

Transdermal vaccine effective in treating Alzheimer's disease in mice

Previous research on an Alzheimer's vaccine proven safe and effective in an animal model was suspended when the initial clinical trial caused brain inflammation and death in a small percentage of patients. A new mouse study has now had success with a transdermal method of delivery (a skin patch), that doesn’t appear to trigger the toxic reaction of past immunization strategies. Further research is needed to assess whether the transdermal vaccine can curb memory loss as well as reduce Ab plaque.

Nikolic, W.V. et al. 2007. Transcutaneous -amyloid deposits without T cell infiltration and microhemorrhage. Proceedings of the National Academy of Sciences, 104 (7), 2507-2512.

Hopeful results from interrupted Alzheimer's vaccine study

Phase 2 of a human clinical trial vaccinating patients with beta-amyloid was halted in 2002 when some participants developed brain inflammation. Participants continued to be monitored, however, and results show that participants whose immune systems mounted a response against beta amyloid performed significantly better on a series of memory tests than those who received a placebo injection (but not on 5 tests often used to diagnose dementia). There were also signs of reduced levels of tau protein (a protein considered a sign of cell death) in those who had an immune response. As a result, new trials are underway, this time using humanized antibodies rather than beta amyloid itself. The antibodies should help trigger the immune system to attack beta amyloid, but will be cleared by the body soon after injection.

Gilman, S., Koller, M., Black, R.S., Jenkins, L., Griffith, S.G., Fox, N.C., Eisner, L., Kirby, L., Boada Rovira, M., Forette, F. & Orgogozo, J-M. for the AN1792(QS-21)-201 Study Team. 2005. Clinical effects of Aß immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 64, 1553-1562.

Fox, N.C., Black, R.S., Gilman, S., Rossor, M.N., Griffith, S.G., Jenkins, L. & Koller, M. for the AN1792(QS-21)-201 Study Team. Effects of Aß immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology, 64, 1563-1572.

Progress on Alzheimer's vaccine

Efforts to create a vaccine for Alzheimer’s have been hindered by potential side effects — some human participants in an earlier trial developed severe inflammation in the brain. A mouse study has now substantially increased the safety of the vaccine by including a tetanus toxin to alter the immune response. Future studies are planned using the herpes virus.

Bowers, W.J., Mastrangelo, M.A., Stanley, H.A., Casey, A.E., Milo, L.J.Jr. & Federoff, H.J. 2004. HSV amplicon-mediated Ab vaccination in Tg2576 mice: differential antigen-specific immune responses. Neurobiology of Aging, available online 25 June 2004.

Mice immunized against Alzheimer's

Using a new vaccine, NYU School of Medicine researchers have prevented the development of Alzheimer's disease in mice genetically engineered with the human gene for the disease. The researchers are optimistic that this new vaccine is safer than one already being tested in early human clinical trials. The new vaccine, modeled on a fragment of a protein called amyloid, which is most frequently implicated in causing Alzheimer's, reduced the amount of amyloid plaque in the brains of mice by 89 percent. At the same time, the vaccine reduced the amount of soluble amyloid beta in the brain by 57 percent. Early clinical trials of the new vaccine could begin within one year.

Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B., & Wisniewski, T. (2001). Immunization with a Nontoxic/Nonfibrillar Amyloid-β Homologous Peptide Reduces Alzheimer’s Disease-Associated Pathology in Transgenic Mice. The American Journal of Pathology, 159(2), 439–447. doi:10.1016/S0002-9440(10)61715-4

A vaccine for Alzheimer's

A vaccine may help prevent and treat the disabling memory loss and cognitive impairment of Alzheimer's disease. Alzheimer's occurs when amyloid-beta peptides accumulate in the brain, forming plaque. While previous studies have shown that vaccinating mutated mice with this amyloid-beta peptide could remove the plaque deposits, there was never any evidence of improvement in brain function, until now. The researchers also believe this study provides the final element of proof that Alzheimer's is initiated by amyloid-beta peptides. The researchers believe clinical trials could begin on human subjects within the year.

Johnson, J. D., McDuff, S. G. R., Rugg, M. D., & Norman, K. A. (2009). Recollection, Familiarity, and Cortical Reinstatement: A Multivoxel Pattern Analysis. Neuron, 63(5), 697–708. doi:10.1016/j.neuron.2009.08.011

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Pilot drug studies

Older news items (pre-2010) brought over from the old website

Tarenflurbil fails clinical trial

In another example of a drug that worked in mice but failed to show a benefit for patients, a study has found that the drug tarenflurbil, which supposedly suppresses the accumulation of amyloid plaque—did not slow cognitive decline or loss of usual daily activities (and was moreover associated with adverse effects including anemia, pneumonia, and herpes zoster). Although the drug showed promise in a small clinical trial, the results were negative in this larger, randomized trial, involving 1684 patients with mild Alzheimer’s. It’s suggested that rather than focusing on Alzheimer's disease and its specific characteristics, we should see dementia as a confluence of three common disease processes—Alzheimer's disease, vascular brain injury, and Lewy body disease.

Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.

Neurogenesis improved in Alzheimer mice

Studies of adult neurogenesis in genetically engineered mice have revealed two main reasons why amyloid-beta peptides and apolipoprotein E4 impair neurogenesis, and identified drug treatments that can fix it. The findings point to a deficit in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission as an important contributor to impaired neurogenesis in Alzheimer’s. While stem cell therapy for Alzheimer’s is still a long way off, these findings are a big step toward that goal.

Gang Li et al. 2009. GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice. Cell Stem Cell, 5 (6), 634-645.

Binggui Sun et al. 2009. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell, 5 (6), 624-633.

Protein identified that counterbalances Alzheimer's proteins

A mouse study has revealed that a protein called Reelin may provide a new approach to tackling Alzheimer’s. Reelin activates and strengthens the response of the NMDA receptor, which plays an important role in coordinating chemical signals between adjacent nerve cells. In the presence of too much amyloid-beta protein (as occurs in an Alzheimer’s brain), the receptor migrates into the cell, reducing the cell's sensitivity to incoming signals. However, with strong concentrations of Reelin, the receptor remains active and the cell continues receiving normally. The findings also make a connection with ApoE4 — the receptor that binds to ApoE also binds to Reelin, and is part of the complex that controls the sensitivity of the NMDA receptors.

Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009). Reelin signaling antagonizes β-amyloid at the synapse. Proceedings of the National Academy of Sciences, 106(37), 15938-15943. doi: 10.1073/pnas.0908176106.

Epilepsy drug may help Alzheimer's patients

A study involving genetically engineered mice has found that mice given the anti-seizure drug valproic acid soon after onset of the disease showed improved memory and reduced plaques. The acid worked by blocking the cascade of reactions that leads to beta-amyloid plaques. Valproic acid helped mice less as their disease progressed.

Qing, H. et al. 2008. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. The Journal of Experimental Medicine, Published online October 27.

New drug for Alzheimer’s

A pilot study of 321 people with mild and moderate Alzheimer's disease has found that those who took the new drug Rember for 50 weeks demonstrated a dramatically smaller reduction (81%) in mental decline compared with those on the placebo. Those on rember did not experience a significant decline in their mental function over 19 months, while those on a placebo got worse. Rember is the first drug to act on the tau protein. A "phase 3" trial is planned for next year, involving a larger group of people with the disease, and if that is successful, the drug could be available by 2012.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

Early study reveals new drug could improve executive function in Alzheimer's patients

A trial of a new drug called PBT2 has been found to improve two indicators of executive function in patients with Alzheimer's disease, and reduces levels of amyloid β in the cerebrospinal fluid. There was no significant effect on memory, but this could be because memory functions deteriorate more slowly than executive ones during the early stage, making changes harder to detect in such a short study. The parent compound to PBT2 is clioquinol.

Lannfelt, L. et al. 2008. Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. The Lancet Neurology, 7 (9), 779-786.

Dimebon significantly improves Alzheimer's symptoms

A study involving 183 Russian patients with mild-to-moderate Alzheimer’s has found that a drug previously used as an antihistamine (dimebon) significantly improved cognitive performance. Moreover, it demonstrated increasing benefits over 12 months, which no currently approved therapies do.

Doody, R.S. et al. 2008. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. The Lancet, 372 (9634), 207-215.

Tarenflurbil slows decline of mild Alzheimer's patients

A trial of 210 patients with mild to moderate Alzheimer’s has found that those with mild Alzheimer’s who received 800mg of tarenflurbil twice a day for a year experienced a rate of decline 46% lower than placebo patients in the activities of daily living scale, and a 36% reduction in the pace of decline in global function.  In those with moderate Alzheimer’s, neither 400mg or 800mg of tarenflurbil had a significant effect, and indeed impacted negatively on a third measure of global function. Patients with mild Alzheimer’s who took 800mg for 24 months had lower rates of decline for all three primary outcomes than those who took it for a shorter period.

Wilcock, G.K. et al. 2008. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurology, 7, 483-493.

Potential new drug target identified

A mouse study has successfully reduced the production of beta-amyloid peptides, and improved memory. These peptides are produced when enzymes cut APP at two places, called the beta-secretase and gamma-secretase sites. Previous research has focused on a mutant beta-secretase sequence only seen in one extended family of patients, the so-called Swedish mutation. The new study identifies a different enzyme, called Cathepsin B (CatB), which works to cut the normal beta-secretase site in more than 99% of patients with Alzheimer’s. Two compounds that inhibit CatB were successfully tested, producing great improvement in memory, as well as reduced brain levels of beta amyloid.

Hook, V.Y.H., Kindy, M. & Hook, G. 2008. Inhibitors of Cathepsin B Improve Memory and Reduce β-Amyloid in Transgenic Alzheimer Disease Mice Expressing the Wild-type, but Not the Swedish Mutant, β-Secretase Site of the Amyloid Precursor Protein. Journal of Biological Chemistry, 283, 7745-7753.

PLMI factor in sleep disturbance for dementia patients

A study of 102 people diagnosed with both cognitive impairment and sleep disturbance (average nightly sleep of seven or less hours and daytime sleep of 30 minutes or longer) found that periodic leg movement disorder (a condition that causes people to jerk and kick their legs every 20 to 40 seconds during sleep) was predictive of reduced total sleep time in older adults with Alzheimer disease and related dementias. Given that sleep disturbance in persons with dementia is a highly prevalent and disabling symptom, and sedative-hypnotics are not recommended, this finding is important because it suggests treatment of periodic leg movements may be beneficial.

Richards, K.C. et al. 2008. Periodic Leg Movements Predict Total Sleep Time in Persons with Cognitive Impairment and Sleep Disturbance. SLEEP, 31(2), 224-230.

Reduction of tau protein protects against Alzheimer’s

A study using genetically engineered mice has found that when tau protein was reduced their memory function was retained and they lived a normal lifespan, even though amyloid-beta levels weren’t affected. They were also made mice more resistant to epileptic seizures.

Roberson, E.D. et al. 2007. Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model. Science, 316 (5825), 750-754.

Marijuana may slow progression of Alzheimer's disease

New evidence suggests that marijuana — which has strong anti-inflammatory effects — may contain compounds that slow the memory loss associated with Alzheimer's disease. Treatment with a synthetic compound similar to marijuana (WIN-55212-2) reduced inflammation in older rats and substantially improved their memories.

The researchers presented their findings October 18 at the annual Society for Neuroscience meeting in Atlanta.

New drug reduces plaque and tangles in Alzheimer's mice

Alzheimer's mice that received a compound known as AF267B for eight weeks performed significantly better on a spatial memory test than untreated mice did. A different memory test that involved associating a place with a shock was not affected. The drug was found to reduce plaques and tangles in the hippocampus but not in the amygdala. AF267B seems to work in part by enhancing the activity of receptors for the neurotransmitter acetylcholine, and boosting the levels of an enzyme called alpha secretase, which blocks the production of beta-amyloid proteins. Suppressing the M1 receptors worsened the condition and performance of Alzheimer’s mice, confirming the important role of M1 receptors in modulating the plaques and tangles characteristic of Alzheimer’s.

Caccamo, A. et al. 2006. M1 Receptors Play a Central Role in Modulating AD-like Pathology in Transgenic Mice. Neuron, 49, 671-682.

New compound stops brain cell degeneration in Alzheimer's disease

A new orally administered compound specifically targeted to suppress brain cell inflammation and neuron loss associated with Alzheimer's disease has been developed. The compound, MW01-5-188WH, is rapidly absorbed by the brain and is non-toxic. It selectively inhibits production of pro-inflammatory proteins called cytokines by glia, giving it relevance for several neurodegenerative disorders. The compound suppressed brain inflammation and neuron dysfunction in the hippocampus and protected against cognitive decline in genetically engineered mice. The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus and attenuated Alzheimer's-like behavioral deficits. The compound represents a new approach to Alzheimer’s therapy.

Ranaivo, H.R., Craft, J.M., Hu, W., Guo, L., Wing, L.K., Van Eldik, L.J. & Watterson, D.M. 2006. Glia as a Therapeutic Target: Selective Suppression of Human Amyloid-Induced Upregulation of Brain Proinflammatory Cytokine Production Attenuates Neurodegeneration. Journal of Neuroscience, 26, 662-670.

Testosterone improves quality of life

A 24-week study involving 16 male patients diagnosed with mild Alzheimer disease and 22 healthy male controls found that Alzheimer’s patients who received daily testosterone treatment showed significant improvement on a quality-of-life instrument that encompasses memory, interpersonal relationships, physical health, energy, living situation and overall well-being, however improvement in memory or other cognitive skills using cognitive tests did not reach significance. Among healthy controls, those receiving testosterone showed a non-significant trend toward greater improvement in self-rated quality of life.

Lu, P.H. et al. 2006. Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men. Archives of Neurology, 63.
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Natural compound from 'pond scum' shows potential activity against Alzheimer's

A compound isolated from a cyanobacterium, a type of blue-green algae (‘pond scum’) shows promise of becoming a natural drug candidate for fighting Alzheimer's. Nostocarboline (the newly isolated compound) is a potent inhibitor of cholinesterase, with a potency comparable to galanthamine.

Becher, P.G., Beuchat, J., Gademann, K. & Jüttner, F. 2005. Nostocarboline: Isolation and Synthesis of a New Cholinesterase Inhibitor from Nostoc 78-12A. Journal of Natural Product, 68(12), 1793–1795.

Gas-blockers might slow down Alzheimer's disease

Beta-amyloid is known to cause brain cells to make an inhibitor of an enzyme that triggers the production of nitric oxide (iNOS). This enzyme is normally turned on during infection and is needed to help immune cells destroy invading pathogens, but it is not normally found in the brain, where it may cause cellular damage that destroys neurons. Although it’s long been known that iNOS is present in the brain lesions of Alzheimer’s patients, it hasn’t been known whether its presence makes things worse. A new study has now shown that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice. The researchers suggest that iNOS inhibitors might turn out to be an effective in slowing the progression of Alzheimer's disease.

Nathan, C. et al. 2005. Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. Journal of Experimental Medicine, 202, 1163-1169.

New memory drug works best in combination with older drug

An experimental drug – a compound known as SGS742 – has been successful in animal studies in improving memory, and is now in human clinical trials. The drug works by blocking certain chemicals that interfere with memory formation, thus enabling better acquisition and retention of new information. It alters the activity of gene control machinery that is important for memory consolidation. It was most effective when used in conjunction with Aricept, an established Alzheimer’s drug.

Helm, K.A., Haberman, R.P., Dean, S.L., Hoyt, E.C., Melcher, T., Lund, P.K. & Gallagher, M. 2005. GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology, 48(7), 956-64.

Chemical decoy shows promise for slowing Alzheimer's

A chemical polymer shows promise in cell culture studies of slowing Alzheimer’s by blocking the toxic brain proteins thought to cause the disease. The likely candidate for any drugs developed from this approach would be people at increased risk of Alzheimer’s, who haven’t yet developed signs of the disease.

Good, T. & Patel, D. 2005. BIOT 421 Development of biomimetic materials for Alzheimer's disease. Presented at 2:05 p.m., Thursday, March 17, at the Convention Center, Room 31A, during the "Tissue Engineering/Biomaterials" symposium at the 229th national meeting of the American Chemical Society.

Antibody treatment partially reverses nerve damage in Alzheimer disease

A mouse study has had success in significantly decreasing structural nerve damage in the brains of mice with Alzheimer’s, by administering an beta amyloid antibody treatment to the brain surface.

Brendza, R.P. et al. 2005. Anti-Aß antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.Journal of Clinical Investigation, 115, 428-433.

Rolipram - a potential new treatment

In a mouse study, a phosphodiesterase 4 inhibitor, rolipram, was found to improve memory in both long-term potential and contextual learning. Rolipram's protective effect is due to its ability to modify gene expression, making brain synapses more resistant to the insult caused by the accumulation of Ab. The beneficial effect of rolipram treatment was found to extend for at least 2 months after the end of one course of the treatment, and was more effective in the later stages of the disease.

Gong, B., Vitolo, O.V., Trinchese, F., Liu, S., Shelanski, M. & Arancio, O. 2004. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. Journal of Clinical Investigation, 114, 1624-1634.

Keeping blood pressure & cholesterol low may help some dementia patients more than Alzheimer's drugs

A comprehensive review of all recent medical studies on mixed dementia, vascular dementia and Alzheimer's suggests that efforts to treat cardiovascular risk factors, especially high blood pressure, may be more effective for many than memory drugs in protecting brain function.

Langa, K.M., Foster, N.L. & Larson, E.B. 2004. Mixed Dementia: Emerging Concepts and Therapeutic Implications. JAMA, 292, 2901-2908.

New type of Alzheimer's drug on trial

A clinical trial is commencing to test the effectiveness of a new type of drug, called Alzhemed, that attacks amyloid. The trial will last 18 months and will enroll about 950 Alzheimer's patients with a mild-to-moderate form of the disease, from centers around the United States and Canada. The drug actually physically combines with amyloid to prevent plaque formation, and is also expected to inhibit the inflammatory response associated with amyloid buildup in Alzheimer's.

Blood pressure drugs may slow deterioration of Alzheimer's

A study involving 162 people in Japan living in long-term care facilities with mild to moderate Alzheimer's disease and high blood pressure has found that certain blood pressure drugs may slow the deterioration of Alzheimer's disease. The results, while interesting, will need to be replicated in carefully controlled, randomized, blinded studies.

Ohrui, T., Tomita, N., Sato-Nakagawa, T., Matsui, T., Maruyama, M., Niwa, K., Arai, H. & Sasaki, H. 2004. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology, 63, 1324-1325.

Anti-cholesterol drug treats Alzheimer's disease in mice

A drug that jams a key enzyme regulating cholesterol (CP-113,818) has been found to drastically reduce the levels of amyloid plaque in genetically engineered mice. The drug has not been tested in clinical trials, but another ACAT inhibitor, avasimibe, is now in final clinical trials as a treatment for vascular disease and atherosclerosis.

Hutter-Paier, B., Huttunen, H.J., Puglielli, L., Eckman, C.B., Kim, D.Y., Hofmeister, A., Moir, R.D., Domnitz, S.B., Frosch, M.P., Windisch, M. & Kovacs, D.M. 2004. The ACAT Inhibitor CP-113,818 Markedly Reduces Amyloid Pathology in a Mouse Model of Alzheimer's Disease. Neuron, 44 (2), 227–238.

Protein found that dissolves amyloid fibers

Amyloid plaque is extremely tough — so tough researchers have been unable to find a means to attack them. A new study suggests that yeast may be the means. Oddly, the yeast protein seems to be involved both in making amyloid fibers, and in dissolving them. The yeast protein Sup35 sometimes forms amyloid fibers in yeast cells — this is part of the cell's normal biology, changing the types of proteins that the cell makes. Another protein — Hsp104 — appears to affect Sup35's ability to form amyloid fibers. When a yeast cell contained either high amounts of Hsp104 or none at all, amyloid fibers never formed. But when Hsp104 levels were small, the fibers flourished. In the latest study, researchers found that small amounts of Hsp104 catalyzed the formation of amyloid fibers, but large levels of the protein actually caused the fibers to dissolve. Interestingly, Hsp104 belongs to a class of proteins that sometimes are influenced by environmental factors.

Shorter, J., & Lindquist, S. (2004). Hsp104 Catalyzes Formation and Elimination of Self-Replicating Sup35 Prion Conformers. Science, 304(5678), 1793–1797. doi:10.1126/science.1098007

Clioquinol slowed progression of cognitive decline in Alzheimer's patients

A new clinical trial has found that the drug Clioquinol slowed the progression of cognitive decline in a group of 36 patients with moderate to severe Alzheimer’s, over a period of 24 weeks. PBT-1 (Clioquinol) is a chemical that binds zinc and copper, and has been shown to lower the levels of beta-amyloid and the associated toxicity in the brains of transgenic mice used as a model of Alzheimer's disease.

Ritchie, C.W. et al. 2003. Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting A β Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial. Archives of Neurology, 60, 1685-1691.

Cancer drug may help against Alzheimer's too

The drug Gleevec, approved for treatment of chronic myelogenous leukemia (CML) over two years ago, has been found to reduce the level of beta-amyloid in immature rat neurons and cultured human cells. The drug also significantly reduced the levels of amyloid peptides in live guinea pigs (who have amyloid peptides comparable to those found in humans). While still preliminary, the work may indicate a new approach to treating Alzheimer’s.

Netzer, W.J. et al. 2003. Gleevec inhibits β-amyloid production but not Notch cleavage. PNAS, 100, 12444-12449.

New Drug for Moderate-to-Severe Alzheimer's

Four drugs — donepezil, galantamine, rivastigmine, and tacrine — are approved for treatment of mild-to-moderate Alzheimer's disease in the U.S., but there are no approved treatments for severe AD. Now an industry-sponsored study has examined memantine for this use. The study involved 252 patients with moderate-to-severe AD, over a period of 28 weeks. Patients were evaluated on 7 tests of cognition, functional capacity, and behavior. Outcomes were significantly better with memantine than with placebo on 4 of these scales, and no significant adverse events were noted. It is not clear yet how clinically meaningful these small improvements are. Memantine has been approved for use in Europe.

Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S. & Möbius, H.J. 2003. Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348, 1333-41.

DHEA supplement shows no effect on Alzheimer's

The supplement dehydroepiandrosterone, or DHEA, had no effect on Alzheimer's patients who took the supplement for six months. A transient benefit on cognitive performance occurred at three months, but was not statistically significant. Of the 58 people who started the study, 46 completed three months of treatment and 33 completed six months of treatment. The small size of the study and the high number of people who dropped out may limit the findings of the study.

Wolkowitz, O.M., Kramer, J.H., Reus, V.I., Costa, M.M., Yaffe, K., Walton, P., Raskind, M., Peskind, E., Newhouse, P., Sack, D., De Souza, E., Sadowsky, C., Roberts, E. & the DHEA-Alzheimer’s Disease Collaborative Research Group. 2003. DHEA treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled study. Neurology, 60, 1071-1076.

Designer chemical offers Alzheimer's hope

Researchers at the University of Illinois at Chicago have designed and synthesized highly potent inhibitor compounds that could lead to an effective treatment for Alzheimer’s disease. In earlier work, the researchers had designed an inhibitor that blocks the action of one of two enzymes thought to be responsible for Alzheimer’s disease. This enzyme, called memapsin 2, is responsible for producing beta-amyloid, which forms the plaques so characteristic of Alzheimer’s disease. The inhibitor was reported in the Journal of the American Chemical Society last year and was shown to be effective in test tube experiments. However, while useful as a model, the inhibitor was too big to be effective in drug therapy. What is needed is a compound small enough to cross the blood-brain barrier. This latest paper reports on a new, smaller, generation of inhibitors designed and tested in the laboratory.

Golestani, N., Molko, N., Dehaene, S., LeBihan, D., & Pallier, C. (2007). Brain Structure Predicts the Learning of Foreign Speech Sounds. Cereb. Cortex, 17(3), 575–582. doi:10.1093/cercor/bhk001

Naturally occurring protein could slow Alzheimer's disease

A cholesterol-lowering protein produced by the body, Apolipoprotein A-1, might be able to slow the progression of Alzheimer's disease.
Everyone has some quantity of Apo-A, in their body. It is produced in the small intestine and the liver and is known to help prevent coronary heart disease. At normal levels, the protein clears cholesterol throughout the body, including in the brain. The scientists speculate that boosting Apo-A levels may also help clear beta amyloid, an important part of the Alzheimer's disease plaques that strangle normal brain cells. Further testing is needed to confirm the role of Apo-A in animals and its relation with Alzheimer's, before any human trials could begin.

Koldamova, R. P., Lefterov, I. M., Lefterova, M. I., & Lazo, J. S. (2001). Apolipoprotein A-I Directly Interacts with Amyloid Precursor Protein and Inhibits Aβ Aggregation and Toxicity†. Biochemistry, 40(12), 3553–3560. doi:10.1021/bi002186k

Why Vitamin E might slow the progress of Alzheimer's

A chemical called methionine (an amino acid found in beta-amyloid) may be the source of the toxic free radicals produced by the amyloid-beta peptide. Recent studies have demonstrated that higher than normal doses of vitamin E may slow the advance of Alzheimer's in some people with late stages of the disease. The current study provides a possible explanation for this link. Vitamin E, an antioxidant, appears to work by destroying free radicals (oxidants) produced by amyloid.

The study was presented at the 2000 International Chemical Congress of Pacific Basin Societies.

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Diet & supplements for Alzheimer's

Older news items (pre-2010) brought over from the old website

Caffeine reverses memory impairment in Alzheimer's mice

Consistent with earlier indications that moderate caffeine consumption may protect against memory decline, a study of genetically engineered mice has found that when the old mice began to show memory impairment, those given caffeine for 2 months performed as well as normal aged mice on cognitive tests, while those given plain drinking water continued to do poorly. The Alzheimer's mice received the equivalent of five 8-oz. cups of regular coffee a day (or two cups of Starbucks coffee, or 14 cups of tea). Moreover, the brains of the caffeinated mice showed nearly a 50% reduction in levels of beta amyloid. The effect appears to be through suppression of both β-secretase and presenilin 1 /g-secretase expression. Caffeine had this effect only on those with Alzheimer’s; normal mice given caffeine through adulthood showed no cognitive benefit.

Arendash, G.W. et al. 2009. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 17 (3), 661-680.

Cao, C. et al. 2009. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. Journal of Alzheimer's Disease, 17 (3), 681-697.

Vitamin B3 reduces Alzheimer's symptoms, lesions

High doses of nicotinamide, a form of vitamin B3, has been found to dramatically lower levels of tau protein in mice with Alzheimer's disease. The vitamin also increased proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. Not only did the vitamin prevent memory loss in Alzheimer’s mice, it also slightly improved cognitive performance in normal mice. Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions. Clinical trials with Alzheimer’s patients are now underway.

Green, K.N. et al. 2008. Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience, 28, 11500-11510.

Vitamin E may help Alzheimer's patients live longer

A study of 847 Alzheimer's patients has found that those who took 1,000 international units of vitamin E twice a day, were 26% less likely to die over a five-year period than people who didn't take vitamin E.  It also appears that taking vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone.

The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12 – April 19.

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

Compound in wine reduces levels of Alzheimer's disease-causing peptides

In cell studies, resveratrol has been found to lower levels of amyloid-beta peptides. Resveratrol is a natural compound occurring in abundance in grapes, berries and peanuts. The highest concentration has been reported in wines prepared from Pinot Noir grapes. The anti-amyloidogenic effect of resveratrol observed in cell cultures does not however necessarily mean that the beneficial effect can result simply from eating grapes or drinking wine. Further research aims to develop more active and more stable compounds.

Marambaud, P., Zhao, H. & Davies, P. 2005. Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid- Peptides. Journal of Biological Chemistry, 280, 37377-37382.

Clinical diagnosis of Alzheimer's may be delayed with donepezil

In a study of people with mild cognitive impairment, those who took the drug donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's during the first years of the trial, but by the end of the 3-year study there was no benefit from the drug. Of the 769 participants, 212 developed possible or probable Alzheimer’s within the 3-year study period; the donepezil group's risk of progression to a diagnosis of Alzheimer’s was reduced by 58% one year into the study, and 36% at 2 years, but no risk reduction at the end of three years. Vitamin E was also tested in the study and was found to have no effect at any point in the study.

Petersen, R.C. et al. 2005. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. New England Journal of Medicine, 352 (23), 2379-2388.

Pilot study points to healing power of turmeric

A study using genetically engineered mice has found that those mice on a diet rich in curcumin (the yellow pigment in the curry spice turmeric) developed 85% few Alzheimer’s plaques then the control group. Curcumin has antioxidant, anti-inflammatory, and cholesterol lowering properties, and has long been used in India as treatment for a variety of ailments. A human trial involving 33 Alzheimer's patients will soon commence.

Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G., Frautschy, S.A. & Cole, G.M. 2004. Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo. Journal of Biological Chemistry, published online ahead of print December 7, 2004
A copy of the full paper can be found on the Journal of Biological Chemistry Web site at

Dietary supplement helps Alzheimer’s

A three-month study of 55 elderly patients with mild or moderate Alzheimer’s found that those given EV-1, a dietary supplement containing, among other things, the putative antioxidant ingredient of red wine, showed no deterioration during the trial. The supplement is designed to interfere with a defective mitochondrial cycle thought to contribute to the metabolic disturbances associated with late onset Alzheimer’s. The Krebs tricarboxylic acid cycle is fuelled by glucose and regulates levels of reactive oxygen species in the body. EV-1 contains glucose, a compound called malate that primes or maintains the Krebs cycle, and resveratrol - the antioxidant component of red wine that is thought to soak up reactive oxygen species. More studies are needed to confirm this result.

The findings were presented in November at the annual meeting of the Society for Neuroscience (SFN) in New Orleans.

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Estrogen for Alzheimer's

Older news items (pre-2010) brought over from the old website

For women over 65, Combined Hormone Therapy increases risk of dementia

Much to the researchers’ surprise and disappointment, a four-year experiment involving 4,532 women at 39 medical centers, has found that combined hormone therapy (involving both estrogen and progestin) doubles the risk of Alzheimer's disease and other types of dementia in women who began the treatment at age 65 or older, although the risk is still small : for every 10,000 women 65 and older who take hormones, 23 of the predicted 45 cases of dementia a year, will be attributable to the hormones. The study also found that the combined hormone therapy produced no improvement in general cognitive function, and in fact had adverse effects on cognition among some women. This supports an earlier study suggesting that, while estrogen is helpful to cognitive function in postmenopausal women, the benefits can be cancelled out by progestin / progesterone. The study also confirmed previous research showing that the combination therapy increased the risk of stroke - previous research has indicated that risk factors for stroke are also risk factors for cognitive decline.

Shumaker, S.A., Legault, C., Rapp, S.R., Thal, L., Wallace, R.B., Ockene, J.K., Hendrix, S.L., Jones, B.N. III, Assaf, A.R., Jackson, R.D., Kotchen, J.M., Wassertheil-Smoller, S. & Wactawski-Wende, J. 2003. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2651-2662.

Rapp, S.R., Espeland, M.A., Shumaker, S.A., Henderson, V.W., Brunner, R.L., Manson, J.E., Gass, M.L.S., Stefanick, M.L., Lane, D.S., Hays, J., Johnson, K.C., Coker, L.H., Dailey, M. & Bowen, D. 2003. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2663-2672.

Wassertheil-Smoller, S., Hendrix, S., Limacher, M., Heiss, G., Kooperberg, C., Baird, A., Kotchen, T., Curb, J.D., Black, H., Rossouw, J.E., Aragaki, A., Safford, M., Stein, E., Laowattana, S. & Mysiw, W.J. 2003. Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative: A Randomized Trial. JAMA, 289, 2673-2684.

Animal studies suggest why estrogen can't help after dementia has developed

Research with rats suggests that nerve cells in the brain called cholinergic neurons are needed for estrogen to help learning and memory. This suggests why starting estrogen after dementia has developed is ineffective.

Gibbs, R.B. 2002. Basal Forebrain Cholinergic Neurons Are Necessary for Estrogen to Enhance Acquisition of a Delayed Matching-to-Position T-Maze Task, Hormones and Behavior, 42(3), 245-257.

Long-term ERT in postmenopausal women with Alzheimer's may worsen memory

A study using female rats investigated the interaction of two conditions known to exist within the brains of female Alzheimer's patients: 1) the presence of chronic neuroinflammation, and 2) having too much or not enough estrogen. They found that rats who had their ovaries removed (to model the condition of post-menopausal women) performed more poorly on a water maze task when they had chronic brain inflammation OR long-term estrogen replacement therapy. Most significantly, those who had both conditions performed much more poorly – beyond what would be expected by either condition alone. That such results extend to postmenopausal women is supported by a 2000 study involving a long term, placebo-controlled study that examined the effects of estrogen replacement therapy on cognitive function in women with mild to moderate Alzheimer's. The effects of ERT were initially beneficial, but the performance of women receiving sustained ERT declined more than that of women receiving the placebo treatment. The results of these studies suggest that postmenopausal women with Alzheimer's disease who undergo long-term estrogen replacement therapy may make their memory loss worse.

Marriott, L.K., Hauss-Wegrzyniak, B., Benton, R.S., Vraniak, P.D. & Wenk, G.L. 2002. Long-Term Estrogen Therapy Worsens the Behavioral and Neuropathological Consequences of Chronic Brain Inflammation. Behavioral Neuroscience, 116 (5), 902-11.

Estrogen patch may improve memory for women with Alzheimer's

A new study suggests that an estrogen skin patch given to women with mild to moderate Alzheimer's disease can improve their memory and attention skills. The study involved only 20 women for eight weeks, and the results will need to be confirmed by a larger-scale study. Research to date has been equivocal about the effects of estrogen on women with Alzheimer's, with some finding a memory-enhancing effect, and others finding no effect. It is speculated that the type of estrogen might be critical. The present study used estradiol, a type of estrogen that has been shown to have an effect on the brain.

Asthana, S., Baker, L. D., Craft, S., Stanczyk, F. Z., Veith, R. C., Raskind, M. A., & Plymate, S. R. (2001). High-dose estradiol improves cognition for women with AD Results of a randomized study. Neurology, 57(4), 605–612. doi:10.1212/WNL.57.4.605

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Anti-hypertensive drugs

Older news items (pre-2010) brought over from the old website

Some blood pressure drugs may help protect against dementia

High blood pressure is a major contributor to the development of all types of dementia. Data from over 1000 participants in the Cardiovascular Health Study, who were free of dementia when they entered the study and who were being treated for hypertension, has revealed that those taking centrally-active ACE inhibitors (which cross the blood-brain barrier) showed significantly lower rates of mental decline. However, non-centrally active ACE inhibitors were associated with an increased risk of dementia compared to those taking other anti-hypertensive drugs. Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Sink, K.M. et al. 2009. Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension: Results From the Cardiovascular Health Study. Archives of Internal Medicine,169 (13), 1195-1202.

Blood pressure drugs may cut risk of Alzheimer's by 40%

Analysis of more than 5 million UK medical records has revealed that those taking drugs known as angiotensin receptor blockers (ARBs), used to treat high blood pressure, had a 35-40% lower risk of developing Alzheimer's disease and similar neurodegenerative disorders. The drugs also appeared to slow the progression of Alzheimer's disease, reducing deaths, admissions to nursing homes and certain symptoms of the condition by up to 45%. The drugs were of most benefit to patients who had experienced a stroke. The most common ARBs are marketed as candesartan, losartan and irbesartan. In the next few months, the study will be repeated using US medical records of a further 3 million patients. It’s reported that the analysis has also identified other drugs that appear to prevent Alzheimer's and some that make the condition worse. A combination of ARBs with other drugs may reduce the risk of dementia by more than 50%.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

Anti-hypertensive drug may help prevent and treat Alzheimer's disease

A review of more than 1,500 drugs commercially available for treatment of other disorders, to determine their potential value in treating Alzheimer's disease, identified 7 out of 55 candidate drugs commonly prescribed for the treatment of hypertension as capable of significantly preventing beta-amyloid production. Only one of these drugs — Valsartan — was shown to have a marked in vitro effect, and this drug has now been shown to reduce the severity of Alzheimer’s in genetically engineered mice.

Wang, J. et al. 2007. Valsartan lowers brain ß-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. Journal of Clinical Investigation, 117, 3393-3402.
Full text available at:

Some hypertension drugs may help reduce dementia risk

Data from the Cardiovascular Health Study, a long-term study of cardiovascular risk factors that involved 5,888 people over 65 years old, has studied 1,074 participants who were free of dementia when they entered the study and who were being treated for high blood pressure. They found use of a class of high blood pressure medicines that are centrally active ACE inhibitors was associated with lower risk of cognitive decline. The benefit did not result from ACE inhibitors in general, only to those that are centrally active (which means they can cross the blood brain barrier). Centrally acting drugs include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Wolozin B, Lee A, Lee A, Whitmer R, Kazis L. Use of angiotensin receptor blockers is associated with a lower incidence and progression of Alzheimer disease. Presented at: International Conference on Alzheimer’s Disease. CA, USA, 26–31 July 2008 (Abstract O1-05-05).

Hypertension drugs might help Alzheimer’s

A project to determine whether drugs that are already commercially available for treatment of other disorders might help in treating Alzheimer’s disease using in vitro methods has identified several hundred drugs as having promise in preventing beta-amyloid build-up, of which seven are commonly prescribed to treat hypertension. One drug in particular was identified as effective in blocking the accumulation of beta-amyloid in the brain and preventing the deterioration of cognitive performance: Propranololo-HCL (Inderal), a drug widely prescribed to treat high blood pressure in elderly patients. Of course, clinical trials will need to occur before this can be confirmed.

The research was reported at the American College of Neuropsychopharmacology’s (ACNP) annual conference December 3 - 7, 2006, in Hollywood, FL.

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Anti-inflammatory drugs

Older news items (pre-2010) brought over from the old website

Pain relievers don’t prevent Alzheimer's in the very elderly

In contrast to a number of studies indicating benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing Alzheimer’s, a large, long-running study following 2,736 members of a healthcare delivery system for 12 years, has revealed that not only did use of these drugs not reduce the risk of developing dementia, the risk among these very elderly (most were over age 83 when they developed dementia) was 66% higher among heavy NSAID users than among people who used little or no NSAIDs. Heavy use was defined as having prescriptions for NSAIDs at least 68% of the time in two years. Although this seems to contradict earlier research, it may be consistent with the theory that NSAID use delays the onset of Alzheimer's – thus, studies of younger NSAID users would show fewer Alzheimer's cases, while groups of older people might show more cases.

Breitner, J.C.S. et al. 2009. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology, Published online April 22, 2009.

Inflammatory response to infection and injury may worsen dementia

Systemic inflammation – inflammation in the body as a whole – is known to have direct effects on brain function, but there has been little research into the impact of systemic inflammation on the progress of dementia and neurodegenerative diseases. Now, in a study to mimic the effect of bacterial infection in people with dementia, a mouse study has revealed that that the inflammatory response to infection in mice with prior neurodegenerative disease leads to exaggerated symptoms of the infection, causes changes in memory and learning and leads to accelerated progression of dementia.

Cunningham, C. et al. In press. Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease. Biological Psychiatry.

Anti-inflammatory drugs do not improve cognitive function in older adults

Previous studies have suggested that nonsteroidal anti-inflammatory drugs are associated with a lower risk of developing Alzheimer’s. A clinical trial involving over 2000 older adults (70+) with a family history of Alzheimer’s disease compared a twice daily treatment of 200 milligrams of either the NSAID celecoxib, or the NSAID naproxen sodium, or a placebo. The trial lasted from March 2001 to December 2004. The study found not only that NSAIDs didn’t improve cognitive function, but that naproxen (but not celecoxib) was associated with significantly lower cognitive performance.

ADAPT Research Group. 2008. Cognitive Function Over Time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Archives of Neurology, 65(7), (doi:10.1001/archneur.2008.65.7.nct70006).

Ibuprofen linked to reduced risk of Alzheimer's disease

A very large five-year study of older veterans (55+) has found that those who  used ibuprofen for more than five years were more than 40% less likely to develop Alzheimer’s disease. Results also showed that the longer ibuprofen was used, the lower the risk for dementia. Other types of NSAIDs, such as indomethacin, were associated with a 25% reduced risk, however others, such as celecoxib, didn’t show any benefit. There was no obvious connection between those which were associated with reduced risk and those that weren’t. It may be that the effect is a product of some other cause.

Vlad, S.C. et al. 2008. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology, 70, 1672-1677.

Ibuprofen, aspirin, naproxen may be equally effective at reducing Alzheimer's risk

And demonstrating that the jury is still out on NSAIDs, a review of six studies has found that people who used NSAIDs had a 23% lower risk of developing Alzheimer’s disease compared to those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken. However, the researchers were specifically looking for a difference between those NSAIDs that lower Aβ1-42 amyloid, which was what they didn’t find — and this agrees with the finding of the large veteran study. The findings of this study then may be taken as supporting the view that specific NSAIDs may be of benefit rather than a particular class of them.

Szekely, C.A. et al. 2008. No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology, 70, 2291-2298.

Low dose aspirin does not protect women against cognitive decline

Evidence that aspirin and other anti-inflammatory drugs may protect against dementia has been inconclusive. Now a large, long-running study involving 6,377 women aged 65 years or more, over ten years, has found that those who took low dose aspirin (100 mg on alternate days) performed at similar levels to a placebo group on cognitive tests. However, there was evidence of benefit in one very specific area of cognition: category fluency.

[850] Kang, J H., Cook N., Manson JA., Buring J. E., & Grodstein F.
(2007).  Low dose aspirin and cognitive function in the women's health study cognitive cohort.
BMJ. 334(7601), 987 - 987.

Full text is available at

Conflicting results about benefit of anti-inflammatory drugs

It’s long been known that patients regularly taking nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, seem to have less risk of developing Alzheimer's. It’s been suggested that this might mean that Alzheimer's is a product of inflammation in the brain, and that damage happens when the microglia, the brain's immune cells, become overactive and attack healthy neurons. A new study of autopsy brain tissue, and of in vitro rat cultures indicates that, on the contrary, what’s happening is that, as microglia age, they lose their ability to protect the brain. Moreover, the latest study into the effects of anti-inflammatory drugs found no benefit for those suffering from Alzheimer’s. Indeed, it is possible that such drugs might exacerbate the problem. It is speculated that microglia may have the potential to both protect and attack neurons. The key may lie in the way microglia interact with beta-amyloid protein.

Anti-inflammatories lower Alzheimer disease–related protein levels in mice

Following earlier research showing three commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) were capable of selectively lowering the levels of Abeta42 (an isoform of the amyloid beta protein) in mice, investigation of 20 commonly used NSAIDs found 8 FDA-approved drugs successfully lowered Abeta42 levels in mice at doses achievable in humans.

Eriksen, J.L. et al. 2003. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aß42 in vivo. Journal of Clinical Investigation, 112, 440-449.

Anti-inflammatories offer some protection against developing Alzheimer's

A review of 9 observational studies that examined the role of NSAID use in preventing Alzheimer's disease found the pooled relative risk of Alzheimer's disease among users of NSAIDs was 0.72. The risk was 0.95 among short term users (< 1 month), 0.83 among intermediate term (mostly < 24 months) and 0.27 for long term (mostly > 24 months) users. The pooled relative risk in 8 studies of aspirin use was 0.87. It was concluded that NSAIDs offer some protection against the development of Alzheimer's disease.

Etminan, M., Gill, S. & Samii, A. 2003. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ, 327, 128.

Buildup of amyloid plaques linked to gene inhibition

Examination of genetically engineered mice and of brain tissue from deceased Alzheimer's patients has found that the buildup of amyloid plaques in the brain dramatically inhibits six genes known to be important for the formation of new memories. The finding suggests a new approach to the treatment of Alzheimer’s disease, combining amyloid-lowering treatment with other strategies designed to block the effect of amyloid on these genes.

Dickey, C.A. et al. 2003. Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice. Journal of Neuroscience, 23, 5219-5226.

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