Researchers say rule out depression, anxiety, unemployment and other stresses before blaming cognitive impairment for everyday difficulties

One in five people living with HIV in a European study reported a decline in everyday functioning as a result of cognitive problems such as memory loss, difficulties in solving problems, poor concentration or reduced attention span, researchers from the CIPHER study group report in the Journal of Acquired Immune Deficiency Syndromes.

But, researchers say, people who reported these problems were also more likely to have comorbid conditions, to be depressed or anxious, to be unemployed and experiencing difficulties in affording basic needs, and ought to be assessed for these problems first before concluding that the underlying problem is a physical decline in cognitive function.

“All our observed associations may have multiple explanations, and causality could be in either direction,” comment the authors. “These results imply that patients who report symptoms of cognitive impairment, or declining everyday function, should be assessed for depression, anxiety, concomitant medical conditions and financial difficulties. Failure to recognise these important elements of patients’ lived experiences risks diagnostic delay, failure to address important needs, unnecessary investigations and further anxiety.”


cognitive impairment

Loss of the ability to process, learn, and remember information. Potential causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment, Alzheimer’s disease and HIV-associated neurocognitive disorder (HAND). 


A feeling of unease, such as worry or fear, which can be mild or severe. Anxiety disorders are conditions in which anxiety dominates a person’s life or is experienced in particular situations.


A mental health problem causing long-lasting low mood that interferes with everyday life.


When using a diagnostic test, the probability that a person without a medical condition will receive the correct test result (i.e. negative).

activities of daily living

Daily tasks that are key to person’s ability to take care of themselves, including eating, bathing, dressing, using the toilet, controlling bladder and bowels, and getting out of bed or a chair without assistance.

Previous research has detected a high prevalence of cognitive impairment in people with HIV. In many cases, this is so mild that it has no impact on daily function.

A standard test used to diagnose progression from asymptomatic to mild neurocognitive impairment is an assessment of self-reported difficulties with activities of daily living (ADLs). The standard test includes an assessment of 16 separate activities. Progression is defined as declines in two or more ADLs attributed by the individual to cognitive difficulties.

Investigators from the European CIPHER study wanted to assess the validity of this assessment and to determine the factors associated with declines in ADLs and symptoms of cognitive impairment in a cohort of 448 adults recruited between 2011 and 2013.

The participants completed a series of computerised and pen-and-paper tests and questionnaires. Self-reported information was collected on employment, income, educational attainment and substance use. The investigators also collected clinical data from the patients’ notes.

The participants were overwhelmingly white (87%), male (84%) with a mean age of 46 years. The majority (89%) were taking antiretroviral therapy, with 81% having an undetectable viral load. Median CD4 cell count was 550 cells/mm3 and the average duration of diagnosed HIV infection was ten years.

Self-reported decline in two or more ADLs was present in 31% of people, of which 21% attributed their decline to cognitive problems. The most commonly reported difficulties were experienced in social activities, work, housekeeping and reading or watching television.

A number of factors were associated with a self-reported decline in ADLs attributed to cognitive impairment. Models adjusted for age, sex, ethnicity, education and study site showed a significant association between decline in ADLs and poorer speed/reaction time and attention and working memory – all key measurements of cognitive impairment. Other factors included difficulty affording basic needs, being unable to work or unemployed, depression, anxiety and being diagnosed with HIV for at least five years.

The investigators also found that several factors were associated with self-reported symptoms of cognitive impairment. These included poorer performance in tests used to assess cognitive impairment, including impaired speed/reaction time, attention/working memory, verbal memory and verbal fluency. Other significant factors included lower levels of educational attainment, co-morbidities, poverty, being out of work, anxiety, depression and ten or more years since HIV diagnosis.

“The relationship between cognitive impairment, low mood and functional decline are complex and multidirectional,” write the researchers.

The tests used to assess declines in ADLs and cognitive impairment did not have levels of accuracy that would be acceptable for diagnostic purposes. The ADL assessment had a sensitivity of 40% and a specificity of 78%, with the measurements of cognitive impairment having a sensitivity of 48% and specificity of 69%. This finding implies that only half of the true cases of cognitive impairment would be diagnosed and that almost one-third of people would be incorrectly classed as having cognitive impairment.

The researchers concluded that other research groups and physicians need to be careful in their use of tests of everyday functioning, and in particular, to pay attention to depression as a reason for any changes. They point out that a previous study of the same population by their group found that poor scores on tests of cognitive impairment, especially those measuring speed of recall or decision-making, were associated with severe depressive symptoms. They suggest that further work is needed to shed light on this association, and in particular, to test whether interventions to improve mood and anxiety have the effect of improving scores on cognitive tests – and peoples' perceptions of their memory and other cognitive functions.


Laverick R et al. Self-reported difficulties with everyday function, cognitive symptoms and cognitive function in people with HIV. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0000000000001468 (2017).