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Losing our minds?
For many of us living with HIV, dementia is a frightening subject. We can imagine coping with many of the ills HIV might throw at us, but not if it robs us of the very thing that does the coping – our sense of self.
Those of us who have known elderly relatives affected by dementia know only too well what the so-called ‘second childhood’ looks like and how it robs people of their identity and independence.
So when an aidsmap.com headline in February declared: “Over-50s at increased risk of cognitive impairment, even with HAART”1, my guess is that many of us were concerned.
Michael Carter’s report was based on a special supplement in the scientific journal AIDS, which documented recent research aimed at finding if there was an increase in dementia and/or mental illness (as we will see below, it’s very important to distinguish between the two) among people over 50 with HIV. Most alarming was a study that found that more than one in five HIV-positive people over 50 had dementia, and that HIV-positive people in general were three times more likely to experience cognitive impairment than the general population.
This seemed particularly worrying to me, since, at 47, I (like a significant number of ATU readers) am approaching the age at which these deficits were observed. In fact, an estimated 11% of people with HIV in both the US and the UK are already over 50 years old.
Whatever happened to AIDS Dementia Complex?
The first associations between AIDS and brain disease were made back in 1986, when two New York neurologists unveiled alarming findings in the Annals of Neurology.2 They concluded that up to a third of their patients with AIDS had a specific group of deficits in cognitive (thinking) and motor (movement) skills – disabilities they named AIDS Dementia Complex (ADC).
This was followed a year later by a report in the Annals of Internal Medicine3, which found neuropsychological deficits in many people with asymptomatic HIV disease. These deficits took characteristic forms, such as poor concentration, poor memory and loss of fine motor co-ordination.
However, the findings of these early studies were criticised at the time by others working in the field, including Dr. Pepe Catalan, Consultant Psychiatrist at London’s Chelsea & Westminster Hospital, whose own studies suggested that although HIV might have subtle mental effects, frank dementia was quite rare.
“The original Annals of Neurology paper was based on autopsies of people who had died, and weren’t necessarily representative of all people with AIDS,” explains Dr. Catalan. “They were patients who had been specifically referred for neurological observation. In addition, what they called AIDS Dementia Complex was a loose diagnosis. I wrote the following in a 1993 paper: ‘It is clear that the original description included more than dementia in the usual sense of the word, and that patients who had a variety of neurological and, possibly, psychiatric disorders were grouped together under a novel label.’ 4
“Using standard definitions, the figures came right down,” Dr. Catalan continues. “We found that the pre-1996 prevalence of classical dementia in people with AIDS was no more than 7% in the last year of their life.
“Instead, we started talking about ‘MCI’ – Minor Cognitive Impairment. This, which is not uncommon in people with HIV, essentially means being a bit slow, a slightly advanced aging. You behave as if you’re ten years older than you are.
“When HAART came along, AIDS-related dementia became a rarity. I’ve seen two or three cases in the last three years, in people diagnosed very late or who don’t seek HAART till very late, and it is difficult to get them back to normal. We also see cases of people who get physically better on HAART, but whose brain impairment doesn’t improve and turns out to be caused by something else – in some cases, alcohol abuse.
“But we were wondering what was going to happen as the population aged. We did do a case notes study in 1998 of people over 50 referred to the psychological medicine service from the Chelsea & Westminster HIV clinic. We found some form of neurological impairment to be more common in people over 50 compared with younger people – the rates were 13% and 4%, respectively.
“But remember, these were people taken from the one-third of HIV patients who get referred because they have some sort of psychological complaint in the first place. We certainly haven’t seen the amount of impairment that these US papers claim.”
The Becker study in AIDS
However, several studies in the AIDS supplement certainly suggest much higher rates of brain impairment in people over 50.
James Becker of Pittsburgh University and colleagues5 recruited 289 HIV-positive and 124 HIV-negative people into a study that subjected them to a battery of psychological tests designed to see how well they performed at specific tasks.
The basic findings certainly sound alarming. The HIV-positive individuals were three times more likely to be impaired either by dementia or by a milder degree of impairment that Becker termed ‘CIND’ – Cognitively Impaired, No Dementia.
Amongst the HIV-positive group, only 69% fit the definition of having ‘normal’ functioning compared with 89% of the HIV-negative group. Across all ages, 22% of HIV-positive individuals were found to have CIND and 9% had dementia.
When the HIV-positive over-50s were looked at specifically, no fewer than 22% of them had dementia, compared with none of the HIV-negative over-50s.
However, when one looks into Becker’s results more deeply, they are not quite what they seem.
When the same tests were performed again a year later, the results were actually better. Of the original 289 HIV-positive people, 169 (58%) returned and 83 of the 124 HIV-negative people (67%) returned for more testing – the rest were lost to follow-up. This time the rates of CIND and dementia in the HIV-positive people were ‘only’ 15% and 4.7% respectively.
Additionally, Becker defined both CIND and dementia very broadly. To have dementia, a person was only required to have quite low scores on two or more individual tests, which did not have to include memory-specific tests. To have CIND, a person needed only to have quite low scores in just one test area. For example, you could be fine at doing everything else but, say, be bad at naming animals starting with ‘s’ – which is a standard verbal fluency test.
“Forty per cent of the people in Becker’s study didn’t even notice they were impaired, and I can tell you that when patients start developing dementia, they definitely notice and are frustrated by their impairments,” concurs Dr. Catalan. “Again, a very loose definition of ‘dementia’ is being used.”
What is more, there are all kinds of conditions that can affect memory, thinking or movement, and HIV-positive people may be more prone to these conditions than other people. For example, depression, poor sleep or the effects of too much alcohol may profoundly affect concentration.
Another concern is that Becker’s sub-category of people over 50 was really very small. Only 22 HIV-positive people were over 50 and a scant three people were HIV-negative. With groups this small, it is highly likely that some of the results could be due to chance.
Most importantly, however, only 17% of Becker’s HIV-positive participants were on HAART, so this study does not measure dementia in a population where the majority are on HAART, as is the case with people with HIV in the UK.
“This study does suggest that there may be increased incidence of cognitive impairment in the over-50s, possibly of a mild to moderate nature, but it’s nothing to be overly concerned about,” concludes Dr. Catalan, “particularly for people on HAART.”
The other studies in AIDS
Igor Grant and colleagues6 compared neuro-psychological abilities in 67 HIV-positive individuals aged at least 50 with those in 52 HIV-positive people aged 35 or less. He found that 64% of the over-50s had at least one deficit in one of seven cognitive or motor ‘domains’, compared with 54% of those under 35. Grant specifically excluded individuals who were current alcohol or substance abusers. However, the numbers in his study were so small that the differences between the over-50s and the under-35s did not achieve statistical significance.
Additionally, the study participants had quite advanced HIV infection: 69% of those under 35 had an AIDS diagnosis, as did 76% of the over-50s. Despite this, only 55% were on HAART, and, of these, 51% of the older group and 28% of the younger group had undetectable viral loads.
Amy Justice and colleagues7 compared psychiatric and cognitive disorders among HIV-positive and HIV-negative patients in the care of the US army veterans’ medical system.
They took results from an intensive study of a small group of patients and used them to calibrate results from quicker but less accurate questionnaires of the entire patient group. The group was large enough to include HIV-positive and -negative people in their 60s and 70s – not a feature of the previous two studies.
They found, as expected, that memory problems increased with age in both HIV-positive and HIV-negative individuals. However, people with HIV had a higher rate of memory problems than those who were HIV-negative, by between six and 14 percentage points according to age group. When people with depressive symptoms were excluded, the HIV-positive people had a higher rate of memory problems in their 60s than HIV-negative people did in their 70s.
But the ‘big story’ of this study was of the psychological factors that were not specifically to do with organic neurological impairment. Contrary to popular wisdom, it has been found that older people tend to have lower rates of depression than younger people. However, depression rates in the older HIV-positive people stayed quite high compared with similarly aged HIV-negative people. So did rates of drug abuse, with, for instance, 24% of HIV-positive people in their 60s reporting recreational drug use compared with 10% of HIV-negative people. This may, however, include phenomena such as ‘medical marijuana’ use for symptom control.
Pepe Catalan comments: “They didn’t match the HIV-positive people with HIV-negative people who had other chronic medical conditions, like cancer or renal impairment. Essentially they were comparing healthy old people with less healthy ones. Nor were they controlling for risk factors like being gay, so we may just be seeing that older gay people are less happy than older heterosexuals.”
Another study8 that specifically looked at dementia and organic cognitive impairment was of a group called the ‘Hawaii Aging with HIV Cohort’. This was a prospective study of a group of older people specifically followed to see what problems they developed with age. Hawaii is a good location for a study like this, since 20% of the HIV-positive people in this state are over 50.
It found that whereas 88% of HIV-positive people aged 20-40 had normal or near-normal neuro-cognitive functioning, only 58% of those over 50 did.
This looks like a conclusive result. However, Pepe Catalan stresses that this study did not use the very specific psychological tests used by the other studies, but only a doctor-evaluated estimation of how well a patient is coping, called the Memorial Sloan Kettering Scale.
He says: “It’s a very inaccurate measurement of functioning. It doesn’t even require the doctor to ask the patient how they are, so it can be easily distorted by physician bias.”
The final study9 in AIDS which looked at organic brain impairment performed brain scans on people with HIV to see what changes were happening in the brain. It found that HIV infection was causing damage to cells in a part of the lower brain called the basal ganglia, and that this increased with length of infection. There was also less serious damage seen in higher cortical areas, which did not increase with length of infection.
Whereas the cortex controls higher functions like thinking, the basal ganglia control impulses towards movement. This is the same area that is damaged in Parkinson’s disease, which may explain why a degree of mild motor impairment is the most common neurological symptom seen in people with AIDS.
However, this study specifically excluded people on HAART – so what it really measures is the damage resulting from untreated HIV infection.
Use it, don't lose it
The AIDS studies do seem to show that as we get older we may expect to develop minor – and in a few cases major – motor, cognitive and memory problems sooner than HIV-negative people our age.
However, it is unclear whether these are the results of HIV infection or other factors to which people with HIV are prone. Co-factors such as depression, lower testosterone levels, and alcohol and drug use can all affect mental functioning at least as much as HIV itself and these factors can, at least, be dealt with by specific therapies or interventions.
Another unknown factor is the effect of HAART’s increased cardiovascular risks. Having high cholesterol levels is another predictor of brain impairment. This is because cardiovascular problems may cause tiny strokes in small areas of the brain, which could build up into a picture of dementia in the long run.
Smoking is also a very significant factor here, and giving up cigarettes may be one of the best ways someone with HIV can protect themselves against the risks of dementia and cardiovascular problems as they age.
Lastly, all but end-stage dementia is at least partially preventable by pursuing a life with a high level of intellectual stimulation and social interaction. This is sometimes called ‘use it, don’t lose it’.
A study published in the British Medical Journal10 recently followed 2058 people who were born in 1946. One of the findings was that people with good reading scores either in their youth or in their late 40s were much less likely to be showing signs of dementia in their late 50s.
The brain is a very adaptable mechanism and, given the right environment, can often compensate for the gradual loss of nerve cells that comes with age. Leading a healthier and stimulating life can do much to prevent us getting slower as we get older.
Key Conclusions
- AIDS-related dementia is very rare today, usually occurring only in people not on HAART
- However, people over 50 on HAART do appear to have a three-fold higher chance of slowed-down movement or thought processes, or ‘forgetfulness’, than younger people on HAART
- These ‘impaired cognitive functions’ may be very mild, and often do not affect everyday life
- HAART may not be the only cause of these symptoms: depression, poor sleep patterns, smoking, binge drinking and/or drug/alcohol dependence are also important factors
- The best protection from these problems is to take HAART, and to treat depression, sleep problems and any addictions (drug, alcohol, nicotine) to reduce long-term harm
- Leading a stimulating life may also protect your brain from slowing down
References
1.http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2572
2.Navia BA et al. Annals of Neurology 19: 517-524, 1986.
3.Grant I et al. Annals of Internal Medicine 107: 828-836,1987.
4.Catalan J et al. International Journal of STD and AIDS 4: 1-4, 1993.
5.Becker JT et al. AIDS 18 (suppl 1): S11-S18, 2004.
6.Cherner M et al. AIDS 18 (suppl 1): S27-S34, 2004.
7.Justice AC et al. AIDS 18 (suppl 1): S49-S59, 2004.
8.Valcour VG et al. AIDS 18 (suppl 1): S79-S86. 2004.
9.Ernst T et al. AIDS 18 (suppl 1): S61-S67, 2004.
10.Richards M et al. BMJ 328 (7439): 552, 2004.