Premorbid functioning assessments are neuropsychological intelligence tests that aim to estimate the level of neurocognitive and memory function prior to some pathological event, such as neurological traumas like traumatic brain injury or the development of neurological diseases such as Alzheimer’s disease and Parkinson’s disease. The estimate is determined based on the assessments that are performed after the damage or pathological event has occurred. These assessments may also include demographic considerations such as education level and occupational history.
Understanding the premorbid functioning of patients or clinical trial subjects can help determine whether or not a decline in neurocognitive performance has occurred following a pathological event as well as the degree of loss or impairment. Below we explore common premorbid functioning assessments, use cases of premorbid functioning assessments in clinical trials, and limitations of such assessments.
Three of the most common methods for estimating premorbid functioning are the Test of Premorbid Functioning (ToPF), the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), and the National Adult Reading Test (NART). The ToPF is a 10-minute word reading test composed of a list of 70 words that have atypical grapheme-to-phoneme translations. The ToPF aims to estimate premorbid intellectual and memory abilities. Similarly, the NART consists of 50 words with atypical phenomic pronunciation which must be read aloud.
The WAIS-IV is considered to be a more advanced measure of intellectual and neurocognitive abilities. It is a 60- to 90-minute assessment composed of 10 core subtests and five supplemental subtests and can be administered via pencil and paper or on a computer. This assessment produces four index scores that represent core components of intelligence:
Two overarching scores—Full Scale IQ and General Ability Index—can be derived from the assessment results.
Clinical trials that require clinical neuropsychological assessments often need to be able to compare obtained scores with an estimate of neurocognitive function and intelligence prior to a given pathological event.
Premorbid functioning assessments are often used in clinical trials for analyzing neurocognitive health and/or intelligence as a dependent variable while altering independent variables, such as the use of drugs, therapies, and other medical interventions such as sleep, diet, and exercise.
Examples of clinical trials that required premorbid functioning assessments to determine neurocognitive function and intelligence before neurological disease onset or brain damage include the following:
Many clinical trials choose to include a large battery of many different neurocognitive and neuropsychological assessments, as they provide higher data granularity and can provide insight into a wider range of neurocognitive domains to better assess the changes or improvements in overall brain health and the impact on Activities of Daily Living (ADLs) in a more robust manner. For these studies, the battery of tools must be sensitive to intra-individual changes in brain health, as these small changes in neurocognitive function may be indicative of the efficacy of the given independent variable.
To fully understand premorbid functioning for highly complex neurological diseases and disorders, a full battery of neuropsychological assessments is needed. While integrating multiple assessments may be able to provide higher data granularity, it may not be feasible to do so on a large scale or in a remote setting, which is often required for clinical trials. Additionally, many premorbid functioning assessments, such as WAIS-IV, require significant time for administration, interpretation, and reporting, further limiting the feasibility of implementing multiple assessments in clinical trials.
Incorporating an integrated battery of neurological assessments to assess premorbid functioning can greatly improve clinical trial efficiency and provide a means to detect minute changes in neurocognitive function that may not otherwise be detected.
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