“My memory is not what it used to be. Am I just getting older or is this

something I should worry about?”

Issues in HIV-associated Neurocognitive Disorder

Peggy BainClinical Neuropsychologist

St Vincent’s Hospital

Since the introduction of HAART, only a relatively small percentage of HIV +ve individuals will present with significant cognitive impairment (HIV associated dementia),

however,

a much larger percentage will report mild, often subtle, changes in cognitive function – these can be individuals with low CD4 counts through to individuals with normal CD4 counts and undetectable plasma viral load.

Familiarity with typical reports and presentations can help in determining the relevance and importance of the complaints, and whether to seek further assessment.

Types of DementiasThere are many different types of dementia: Alzheimer’s disease,

Vascular dementia, Fronto-temporal dementia, HIV associated dementia, etc. with different underlying pathology and different patterns of impairment. As an example:

HIV associated dementia: typically a fronto-subcortical dementia. Typical impairments include slowing, coordination/motor

difficulties, retrieval based memory difficulties.

Alzheimer’s Disease: a cortical dementia, primarily affects the temporal lobe, parietal lobe and frontal lobe functions. Typical impairments are in new learning and retention of learned

information (rapid forgetting), visuospatial function, language, etc.

A major difference between HIV associated dementia and other dementias?

It is possible for improvement in function to occur in response to treatment with HAART.

Updated terminology – HIV-associate neurocognitive disorder (HAND) – Antinori et al 2007

HIV-associated asymptomatic neurocognitive impairment (ANI)

HIV-associated mild neurocognitive disorder (MND)

HIV-associated dementia (HAD)

HIV-associated asymptomatic neurocognitive impairment (ANI)

Acquired impairment of ≥ 1 sd below the mean in ≥2 ability domains on neuropsychological assessment

Impairment does not interfere with everyday functioning.

No confounds

HIV-associated mild neurocognitive disorder (MND)

Acquired impairment of ≥ 1 sd below mean in ≥ 2 ability domains on neuropsychological assessment.

Cognitive impairment produces at least mild interference in daily functioning (at least 1 of the following)

a) self report of reduced mental acuity, inefficiency in work, homemaking or social functioning.b) Observation by knowledgeable others that the individual has

undergone at least mild decline in mental acuity with resultant inefficiency at work, homemaking or social functioning.

No Confounds

HIV-associated dementia (HAD)

Marked impairment in cognitive functioning, in ≥2 ability domains , typically the impairment is in multiple domains (esp. new learning, slowed information processing and defective attention/concentration). On testing ≥ 2 domains ≥ 2 sd below demographically corrected norms.

Cognitive impairment produces marked interference with day to day functioning (work, home, social activities)

No confounds.

Manifestations of HIV related impairment (Sidtis, 1994)

There are 3 main domains of change: Cognitive change

cognitive slowingforgetfulness word finding difficulties reduced concentration conceptual difficulties

Behavioural changeapathy/ withdrawalflat affectirritability/ emotional labilitypersonality change

Motor changeunsteady gait motor weakness reduced co-ordination tremor

Changes since the introduction of HAART

The features of HAND are more variable now; there are fewer cases characterised primarily by psychomotor slowing.

More variability has been observed in the clinical course. Cognitive impairments might progress, improve, fluctuate or remain static over time (Nath et al 2008).

Complaints warranting further consideration in HIV +ve individuals

Slowing in thinking Difficulty finding words or expressing ideas Forgetfulness (e.g. losing keys, missing appointments, forgetting

things they’ve been told) Losing track of conversations (e.g. starting to say something and then

forgetting what they were going to say next) Losing track of intended actions (e.g. heading into a room and

forgetting what they went in there for) Difficulty doing more than one thing at a time/multi-tasking Difficulty maintaining concentration (e.g. more easily distractible,

needing to reread information to take it in)

Complaints warranting further consideration in HIV +ve individuals (cont.)

Changes in handwriting (writing messier, change in signature) Change in ability to carry out fine motor tasks (e.g. clumsier with

buttons, dish washing) Reduced interest, motivation, or initiation of activity Change in level of conversation (e.g. provides brief responses or

makes little spontaneous conversation, or perhaps more talkative) Increased irritability or emotional lability Disinhibited or elevated behaviour

If it does seem that there has been a change from the individual’s usual level of function, then further assessment needs to be considered.

This might include neurological review, MRI/MRS, other investigations (e.g. blood tests, lumbar puncture), and neuropsychological assessment where available.

Impact of Neurocognitive impairment

Fear of the possibility of dementia can lead to individuals failing to report changes., or they might attribute changes to other factors such as “I’m just getting older” or “I’m no longer working & not mentally stimulated”.

Even subtle impairments can have a significant impact on quality of life for the individual.

Research has demonstrated relationships between impairment and Employment (e.g. ability to maintain or return to work) Driving Medication adherence Mood Fatigue Interpersonal functioning

Benefits of Early Detection

HIV treatments can lead to improvement in cognitive impairment -early detection allows consideration of treatments (e.g. commencing, recommencing, changing drugs or modifying doses). If treated early it can reduce the chance of irreversible impairment.

It can provide reassurance to have difficulties acknowledged and be armed with strategies to assist in managing these.

It might be the case that impairments are not as bad as the individual feared.

It can enable arrangement for appropriate services and supports.

HIV, the aging brain and adherence

The possibility of cognitive impairment is an important consideration in managing medication adherence.

While older HIV +ve individuals generally demonstrate better overall adherence, older HIV +ve individuals with cognitive impairment or drug problems are at increased risk of suboptimal adherence to medications (Ettenhofer et al 2010).

It is also the case that older adults may also be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence.

HIV and the Aging Brain

There is now a focus on increased risk of age-associated, non-aids related morbidity for those on long term HAART e.g. higher rates of cardiovascular disease, diabetes, cancers, bone fractures, liver failure, and cognitive impairment (see Deeks, 2009).

Brew et al (2009) highlight the interplay of various factors in the expression of neurodegenerative diseases in HIV - the interplay of HIV infection, age, medication, and individual susceptibility/risk factors.

Risk factor reduction is an aspect that can be targeted e.g. regular mental and physical exercise; cardiovascular targets such as smoking cessation, control of hypertension and cholesterol levels; and improvement in glucose control.

Multifactorial aetiology of cognitive/behavioural disorders in older HIV +ve adults (Valcour & McMurtray 2009)

The following are factors which might lead to multifactorial cumulative brain impairment with aging:

Potential age-related factors: Cumulative cerebrovascular co-morbidity Chronic immune activation Long term exposure to ARVs Concurrent neurodegenerative disease Altered Blood-Brain Barrier

HIV specific factors: uncontrolled plasma and/or CSF HIV

Other factors: lower educational attainment

HIV +ve individuals with co-existing/co-morbid factors

The presence of various co-morbid conditions might increase the possibility of cognitive impairment – additive effects;

Hepatitis C, Methamphetamine and HIV can independently affect the CNS. Studies have shown that cognitive performance can worsen as the number of conditions increases (i.e. having the 3 led to worse performance than having 2) (e.g. LeTendre et al, 2005).

Alcohol and HIV can independently impair cognitive function, but HIV +ve individuals who chronically abuse alcohol might be at greater risk for accelerated progression of HIV related effects on the brain (e.g. Meyerhoff et al, 1995, Rothlind et al 2005, Sasoon et al 2007).

HIV +ve individuals with co-existing or co-morbid factors and cognitive complaints

It is necessary to consider the nature and time frame of cognitive complaints and how these relate to the co-morbid condition. For example:

Past brain injury with ongoing memory impairment but recent worsening of concentration and memory difficulties.

Reduced use of alcohol or recreational drugs but increasing memory difficulties.

Past episodes of depression but now complaints are qualitatively different or depression is not responding to treatment.

Some Final Basic Considerations

Cognitive impairment can occur in individuals with good CD4 counts and plasma viral loads, so reliance on blood counts can be misleading.

The individual may not think to mention cognitive difficulties when attending a medical practitioner and possibly not be aware that these complaints can arise from HIV. Consideration and routine questioning about cognitive function is an important inclusion in providing optimal clinical care. MMSE is not an appropriate tool for screening.

Incorrectly attributing changes to non-HIV factors (e.g. age, alcohol, drug use, depression) can lead to an individual being denied appropriate or optimal treatment and supports.

Targeting risk factors is another important consideration in trying to reducing the chance of cognitive impairment, especially over the longer term.