A new understanding of why dementia sometimes occurs with HIV, even when treated, may also suggest a new approach to other neurological disorders, including age-related cognitive decline.
HIV-associated dementia occurs in around 30% of untreated HIV-positive patients. Surprisingly, it also is occasionally found in some patients (2-3%) who are being successfully treated for HIV (and show no signs of AIDS).
A new study may have the answer for this mystery, and suggest a solution. Moreover, the answer may have general implications for those experiencing cognitive decline in old age.
The study found that HIV, although it doesn’t directly infect neurons, tries to stop the development of BDNF. Long known to be crucial for memory and learning, the reduced production of mature BDNF results in axons and dendrites shortening — meaning connections between neurons are lost. That in turn, brings about the death of some neurons.
It seems that the virus interferes with the normal process of development in BDNF, whereby one form of it, called proBDNF, is cut by certain enzymes into a new form called mature BDNF. It is in this form that it has its beneficial effect on neuron growth. Unfortunately, in its earlier form it is toxic to neurons.
This imbalance in the proportions of mature BDNF and proBDNF also appears to occur as we age, and in depression. It may also be a risk factor in Parkinson's and Huntington's diseases.
However, these findings suggest a new therapeutic approach.
In which context, it is interesting to note another new study, which has been busy analyzing the effects on brain cells of 2000 compounds, both natural and synthetic. Of the 256 that looked to have protective effects, nine were related to epicatechin, which is found in cocoa and green tea leaves.
While we’ve been aware for some time of these positive qualities, the study specifically identified epicatechin and epigallocatechin gallate (EGCG) as being the most effective at helping protect neurons by inducing production of BDNF.
One of the big advantages these compounds have is in their ability to cross the blood-brain barrier, making them a good candidate for therapy.
While green tea, dark chocolate, and cocoa are particularly good sources, many fruits also have good levels, in particular, black grapes, blackberries, apples, cherries, pears, and raspberries. (see this University of Davis document (pdf) for more detail)
 Bachis A, Avdoshina V, Zecca L, Parsadanian M, Mocchetti I. Human Immunodeficiency Virus Type 1 Alters Brain-Derived Neurotrophic Factor Processing in Neurons. The Journal of Neuroscience [Internet]. 2012 ;32(28):9477 - 9484. Available from: http://www.jneurosci.org/content/32/28/9477
 Nath S, Bachani M, Harshavardhana D, Steiner JP. Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway. Journal of NeuroVirology [Internet]. 2012 . Available from: http://www.springerlink.com/index/10.1007/s13365-012-0122-1
First study: http://www.eurekalert.org/pub_releases/2012-07/gumc-pco070612.php
Second study: http://www.eurekalert.org/pub_releases/2012-08/s-hfp081412.php
HIV-related cognitive impairment is significantly associated with a greater waist circumference, and in older adults, with diabetes.
A study involving 130 HIV-positive people has found that memory impairment was associated with a significantly larger waistline.
Some 40% of participants (average age 46) had impaired cognition. This group had an average waist circumference of 39 inches, compared to 35 inches for those without such problems. Memory impairment was also linked to diabetes in those older than 55 (15% of those with memory problems had diabetes compared to only 3% of those without memory problems).
Waistline was more important than BMI. Unfortunately, some anti-HIV drugs cause weight gain in this area.
The finding is consistent with evidence that abdominal weight is more important than overall weight for cognitive impairment and dementia in the general population.
For more about HIV-related cognitive impairment
 McCutchan JA, Marquie-Beck JA, FitzSimons CA, Letendre SL, Ellis RJ, Heaton RK, Wolfson T, Rosario D, Alexander TJ, Marra C, et al. Role of Obesity, Metabolic Variables, and Diabetes in HIV-Associated Neurocognitive Disorder. Neurology [Internet]. 2012 ;78(7):485 - 492. Available from: http://www.neurology.org/content/78/7/485
More than half of HIV patients experience memory problems and other cognitive impairments as they age. Now analysis of biomarkers in the cerebrospinal fluid have demonstrated how HIV-related cognitive impairment is like Alzheimer's-related dementia, and how it is different. The comparison of 49 HIV patients with cognitive impairments (average age 48), 21 HIV patients with normal cognitive function (average age 43), 68 patients with mild Alzheimer's (average age 74) and 50 normal, healthy controls (average age 50), found similarly low levels of amyloid beta in those HIV patients with cognitive impairments and those with Alzheimer’s — surprising researchers, and confirming an earlier study. Unlike the HIV patients however, those with mild Alzheimer's had significantly higher levels of tau.
 Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR, Kauwe JSK. CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology [Internet]. 2009 :WNL.0b013e3181c5b445 - WNL.0b013e3181c5b445. Available from: http://www.neurology.org/cgi/content/abstract/WNL.0b013e3181c5b445v1
A study involving 40 individuals with HIV, 38 with chronic alcoholism, 47 with both HIV and chronic alcoholism, and 39 controls, has found that although those with only one of these disorders mostly performed at levels comparable to controls on episodic and working memory tasks, those who were both positive for HIV and had a history of chronic heavy drinking were impaired on tests of immediate episodic memory (but not working memory) — meaning that they have trouble encoding new information for long-term memory. The finding is consistent with the fact that the mediotemporal lobe is affected early by both these conditions. Heavy drinking is very common among those infected with HIV.
 Fama R, Rosenbloom MJ, Nichols NB, Pfefferbaum A, Sullivan EV. Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations. Alcoholism, Clinical and Experimental Research [Internet]. 2009 ;33(10):1815 - 1824. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19656122
A compound derived from green tea greatly reduced the neurotoxicity of proteins secreted by the human immunodeficiency virus, suggesting a new approach to the prevention and treatment of HIV-associated dementia.
Brian Giunta reported the findings May 1 at Experimental Biology 2007 in Washington, DC.
Cognitive impairment in people with AIDS is caused when the HIV virus attacks the brain and can be a complicated syndrome resulting in deficits in mood, behavior, motor coordination and thought processes. While the incidence of severe dementia in people with AIDS has decreased significantly, a greater number of people are living with a milder form of cognitive impairment. A study of 54 participants with AIDS and 23 HIV-negative control subjects has found that cognitive impairment in people with AIDS exists in two forms -- one mild, another severe -- each affecting different areas of the brain. Of the 54 participants with AIDS, 17 demonstrated some level of mental impairment. The mild impairment group only showed problems in the area of psychomotor speed, and demonstrated atrophy in the frontal and anterior cingulate cortices. Those in the severe impairment group showed impairments in memory and visual-spatial processing as well as psychomotor speed, and had more significant atrophy that was located in the caudate and putamen.
The findings were presented April 5 at the American Academy of Neurology 58th Annual Meeting in San Diego.
A new imaging study has revealed a startlingly selective pattern of destruction inflicted by AIDS on brain regions. Only motor, language and sensory functions were affected. Also surprisingly, there was no difference in brain tissue loss between those taking antiretroviral drugs and those not. It appears that the blood barrier prevents these drugs entering the brain.
 Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2005 ;102(43):15647 - 15652. Available from: http://www.pnas.org/content/102/43/15647.abstract
Treating HIV requires patients to rigorously follow a medication schedule; more than most diseases, the virus easily develops a resistance to the drugs if not taken reliably. Moreover, HIV can cause brain damage, making it more difficult for some patients to remember. A device known as Jerry (more formally, the Disease Management Assistance System) flashes a light and verbally tells the patient the exact dosage and medication to take at the correct time. Of the 58 patients in a recent study, those with Jerry took their medication 80% of the time, while those without did so only 65% of the time. The difference was only significant for those with memory impairment: of the 31 memory-impaired patients, those using Jerry had a 77% adherence rate, while those without Jerry had a 57% adherence rate.
 Andrade ASA, McGruder HF, Wu AW, Celano SA, Skolasky RL, Selnes OA, Huang I-C, McArthur JC. A programmable prompting device improves adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America [Internet]. 2005 ;41(6):875 - 882. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16107989
New evidence suggests that for that those with HIV, the disease, medications, or both, are accelerating what is a normal age-related process.
Although HIV doesn't directly infect neurons, it appears that once it has crossed the blood-brain barrier, it affects supporting cells that can release immune factors that harm neurons. New techniques used on 26 subjects with HIV and 25 matched controls have now found that those with HIV showed decreased brain blood flow to levels roughly equivalent to readings seen for uninfected individuals 15 to 20 years older. It is suggested that HIV, medications, or both, are accelerating what is a normal age-related process. It’s estimated that 14-18% of AIDS patients in the U.S. are more than 50 years old, and this proportion is rapidly growing.
 Ances BM, Vaida F, Yeh MJ, Liang CL, Buxton RB, Letendre S, McCutchan AJ, Ellis RJ. HIV Infection and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging. The Journal of Infectious Diseases [Internet]. 2010 ;201(3):336 - 340. Available from: http://dx.doi.org/10.1086/649899
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