Neuropsychology is an amalgam of many disciplines, influenced by neuroanatomy, neurophysiology, neurochemistry, neuropharmacology, psychology and neurology³, as well as philosophy, physiology and anatomy⁴. Psychometric theory and application, as they relate to appropriate use of data analyses in test construction and the development of normative data, are the very linchpins of neuropsychological assessment and substantiate the theoretical and conceptual networks of the discipline.

The nexus between current neuropsychological theory and practice harks back to ancient philosophical thought³. Ideas such as aestheticism (e.g., is a theory appealing?), rationalism and empiricism still fuel the practice of clinical neuropsychology⁵. Glozman⁶ discusses the influence of Russian contributions dating back to the late 18th century from psychiatrists and neurologists and attributed many changes in neuropsychological practice – including combining both quantitative and qualitative approaches, expansion to include social and personality variables and increasing nosological patient groups – to this influence. A main theme that Glozman⁶ noted was ‘…not so much diagnostic but prognostic…neuropsychological assessment should rather emphasize the subject’s strengths which are important…and predict his/her ultimate integration into society’ (p. 177). The need for a systematic, valid and reliable method of measuring the manifestations of brain function emerged. Test construction thus came on the heels of conceptual and theoretical models of brain function and organization.

Delineating the inception and progression of various neuropsychological tasks is beyond the scope of this chapter. However, we have selected to discuss one very commonly used method for assessing executive functioning to exemplify the manner in which some of our tests have been developed. Executive functioning is a cognitive process involving one’s ability to adapt and respond effectively to environmental demands, novel situations and ultimately deduce efficient and effective ways for completing them. Several ‘tributaries’ of executive functioning have been promulgated, including sequencing behaviours, abstraction, organization and planning. Eling and colleagues⁷ report on the influence of Narziss Ach who designed a paradigm for observing concept formation in the early 20th century. Nonsense words (on cards) were attached on various geometric figures of different shapes and sizes and once these cards were removed, the individual was required to deduce how the words related to the features of the objects. The quintessential element of this task is that one must discover the sorting principle. Goldstein and Scheerer¹ underscored the abstract elements of this task, in which one must be able to abstract from a concrete object, while maintaining insight into other potential ‘choices’. The Wisconsin Card Sorting Test (WCST)⁸ was developed on the basis of these principles. Brenda Milner⁹ ultimately demonstrated that lesions in the dorsolateral prefrontal cortex resulted in shifting problems (i.e., perseverating) and subsequent research has repeatedly confirmed that damage to the frontal cortex is associated with poor performance on this task¹⁰.

Integrity of the perforant pathway (the principal source of input to the hippocampal formation) is essential for normal hippocampal function. In Alzheimer’s disease, it is the pathological changes in this pathway that preclude its normal operation of acquisition of contextual knowledge, presumably due to a disconnection among the hippocampal formation and input from sensory-specific and multi-modal association cortices¹¹. However, as the neuropathology spreads beyond the medial temporal lobe structures to the association cortices of the frontal, temporal and parietal lobes, higher order cognitive deficits result¹². Regarding cognitive assessment in Alzheimer’s disease, it is the juxtaposition of the neuropathological changes along the disease trajectory with administration of specific tests chosen to assess the associated cognitive deficits that is the cornerstone of clinical neuropsychology. The application of statistical methodology provides the intellectual spadework for clinical practice, as the interpretation of test performance requires the understanding of statistical principles underlying test construction and interpretation.

The advent of neuroimaging in the 1970s changed the clinical neuropsychologist’s role from that of lesion detection to one of description of the cognitive sequelae of disease¹³ and/or diagnosis of disease for which imaging is uninformative. In general, there is a chasm between knowledge gleaned from neuroimaging and information gathered through neuropsychological examination. Imaging tells us what (e.g. cerebrovascular accident), where (e.g. anterior cerebral artery) and how (e.g. ruptured aneurysm), whereas neuropsychological examination tells us the consequences, including how much (degree of deficit) and in what way (memory, language, etc.) functioning has been affected.

Neuropsychological assessment in dementia depends on the context of the referral question. In some cases, the neuropsychologist’s role is to determine whether cognitive impairment exists and if so, to assist with the differential diagnosis of its cause. In other cases, diagnosis of the disease causing the dementia has been established and the neuropsychologist is asked to determine areas of cognitive strength and weakness, to assist with the development of compensatory strategies. Neuropsychological assessment is also used to track disease progression through repeated examinations, at times determining whether changes in medication are associated with changes in cognition. In still other cases, neuropsychological assessment provides objective data to assist in determining whether a patient is competent to make independent decisions regarding medical, financial or other matters. Recommendations regarding whether a patient should cease driving or working are also informed by neuropsychological assessment. Thus, the context of the referral, even within the narrow scope of dementia assessment, is important to the information that is provided by the neuropsychologist.

It is quite often the case that clinical neuropsychologists must disentangle ambiguous complaints of declines in cognitive function. Memory complaints, for example, often dissemble the extent and typology of cognitive deficits. What can present as a memory deficit may be related to the bigger picture of a breakdown in semantic knowledge (e.g. naming), or difficulties with executive function that can affect one’s ability to carry out a series of everyday tasks. The pattern of performance exhibited on a neuropsychological examination provides information with regard to these core and peripheral deficits and in conjunction with a comprehensive anamnesis, offers etiological significance.

The cortical-subcortical distinction proffers a heuristically useful model for describing the pattern of neuropsychological performance in various patient groups, despite observations that this is an oversimplified dichotomy^14,15. This distinction was engendered by the observation of different clinical presentations in patients with cortical compared to subcortical disease¹⁶. Although the prototypical cortical dementia is that caused by Alzheimer’s disease, other diseases, such as frontotemporal lobar degeneration and Creutzfeldt-Jakob disease, are also associated with cortical pathology. Far greater in number, diseases causing subcortical dementia comprise, among others, progressive supranuclear palsy, Parkinson’s disease and Huntington’s disease and are associated with pathological changes involving the thalamus, basal ganglia and related brain-stem nuclei. Cortical diseases typically develop similar cognitive footprints, including deficits in language, learning and praxis, whereas patients with subcortical dementia typically demonstrate impaired attention/concentration, processing speed and executive function, as well as apathy and depression. Although the cortical/subcortical dichotomy is simplistic and does not account for disorders with both cortical and subcortical features (e.g. cortical-basal degeneration¹⁷), this distinction remains useful in the differential diagnosis of dementia.

In clinical practice, the neuropsychologist must make several determinations when the question of dementia is being considered. After the tests are administered and the scores are obtained, these scores are compared against a normative sample; that is, a sample of individuals, typically of the same age, but sometimes of the same race, sex and education as the patient. This comparison yields standardized scores (percentiles, z-scores or t-scores) for each raw score. Upon examination of these standardized scores, the neuropsychologist must consider several questions. First, is the examination normal or abnormal? Second, if it is abnormal, does the examination indicate the presence of a cognitive disorder or dementia? Third, is the pattern of cognitive test performance suggestive of cortical or subcortical involvement? Fourth, what disease is underlying the cognitive disorder?

Abnormal scores on individual tests can be defined by several means. In some cases, a score that is obtained by fewer than a particular proportion (often 2%) of the normal population is considered to be abnormal. However, in a large battery of neuropsychological tests, obtaining several scores that are in this ‘impaired’ range is quite normal¹⁸