Novel neuropsychological instruments for the prodromal and preclinical diagnosis of Alzheimer’s disease

The two-part special issue of Neuropsychology consist of articles examining the latest neuropsychological approaches to the diagnosis of preclinical and prodromal forms of Alzheimer’s disease, with Part I (the September 2023 issueopens in new window) focusing on episodic memory and Part II (the October 2023 issueopens in new window) focusing on perception, short-term and semantic memory, language, and behavioral questionnaires and observations. Guest editors Giovanni Augusto Carlesimo and Maria Stefania De Simone discuss key takeaways.

With this special issue, we aimed to take stock of the latest neuropsychological approaches to the diagnosis of preclinical and prodromal forms of Alzheimer’s disease. To this end, research groups active in this field and representative of numerous neuropsychological traditions from many countries around the world have made contributions of great interest and novelty. Indeed, until a few years ago, it was believed that because episodic memory disturbance is the typical cognitive deficit in early stages of Alzheimer’s disease, the contribution of neuropsychological investigation to the diagnosis of this disease was limited to demonstrating a specific deficit in this function. However, discovering the existence of a long period of the disease in which such memory deficit is not appreciable with normal neuropsychological tools and finding evidence that specific regions of the parahippocampal cortex are the elective sites of neurodegeneration in the preclinical stages of the disease have led to the development of innovative neuropsychological approaches. Some new evaluation methods are able to highlight particular aspects of episodic memory deficits at a very early stage of the disease course in these patients. Others are able to identify cognitive function impairments that are not immediately appreciable on standard neuropsychological examination. These new methods are highly sensitive and specific in documenting deficits at very early stages of disease.

This special issue can contribute to the investigation of early features of cognitive impairment in Alzheimer’s disease by showcasing the role that neuropsychology can play in early disease diagnosis. Currently, diagnostic criteria for this disease are based substantially on the demonstration of altered concentrations of biological markers of the disease found in the cerebrospinal fluid or plasma. A noninvasive examination, welcome by the patient and easily performed and exportable to any cultural and social context and endowed with a high sensitivity and specificity to reveal disorders related to neurodegeneration of the temporomesial structures, can undoubtedly serve as a first-level approach to disease screening that, when possible and indicated, will be complemented by specific biological and neuroimaging approaches. A second contribution that this special issue can make is increasing knowledge about the role that temporomesial structures play in episodic memory and other cognitive domains (e.g., short-term memory, semantic memory, language). It is of absolute significance, in fact, that Alzheimer’s disease is the only neurological disorder that, at least at one stage of its development, specifically involves anatomical structures of this area (e.g., the perirhinal cortex and later the entorhinal cortex and hippocampus), providing relevant information about the role of these structures in a variety of cognitive domains.

A first takeaway from this special issue is that when assessing an older person who is complaining of mild cognitive deficits, it is necessary to abandon the “memory-centric” approach and instead be open to a more comprehensive assessment that takes into account other aspects of cognition related to, for example, perception, semantic memory, short-term memory, and executive functions that can more fully describe the cognitive impairment resulting from the neurodegeneration of Alzheimer’s disease.

Second, even in the analysis of episodic memory disturbance for diagnostic purposes in preclinical forms of Alzheimer’s disease, a change in the traditional perspective is needed. Indeed, attention should be paid not so much to the patient’s overall level of performance (in terms of how much the patient remembers) but rather to the efficiency of specific aspects of their cognitive functioning (e.g., consolidation of the amnestic trace, susceptibility to interference, associative learning, conjunctive and relational binding).

Third, although neuropsychology alone cannot provide absolutely conclusive evidence for a diagnosis of Alzheimer’s disease at an early stage, its nature as a screening tool should be reaffirmed. Indeed, when a patient presents with discomfort regarding their decline in cognitive efficiency, a neuropsychological exam may offer reliable data about the malfunctioning of specific brain areas and thus enable the clinician to formulate diagnostic hypotheses that may be corroborated with specific biological investigations.

Most of the articles in this special issue reported evaluations of the diagnostic reliability of tests or questionnaires intended to distinguish healthy individuals from individuals who complained of mild cognitive deficits and for whom there was diagnostic suspicion of preclinical Alzheimer’s disease. Some of the neuropsychological tools used worked well in distinguishing healthy older people from patients with incipient Alzheimer’s disease, even in situations where common cognitive screening tests were unable to reveal differential cognitive profiles. In this sense, the main practical implication arising from these articles is to make available innovative tools that can support the diagnosis of Alzheimer’s disease at a very early stage of its course. Further studies will, of course, be needed to standardize and collect normative data on the tests that have shown the most promise to provide neuropsychologists with effective tools to use in their clinical practices.

This article is in the Neuroscience and Cognition topic area.

Carlesimo, G. A., & De Simone, M. S. (2023). Special issue on “Novel neuropsychological instruments for the prodromal and preclinical diagnosis of Alzheimer’s disease”. Neuropsychology, 37(6), 623–627. https://doi.org/10.1037/neu0000907opens in new window

Giovanni Augusto Carlesimo, PhD, is an associate professor of neurology at Tor Vergata University in Rome. He works as a medical director at the Santa Lucia Foundation in Rome. His main area of research concerns the qualitative profiles of memory disorders in dementia syndromes underlain by various etiologies.

Maria Stefania De Simone, PhD, is an assistant professor of psychology at the Niccolò Cusano University of Rome and a researcher at the Neuropsychology of Memory Lab of the IRCCS Santa Lucia Foundation of Rome. Her research interests are in early detection, diagnosis, and cognitive intervention for people with preclinical and prodromal forms of dementia.