Now is the Time to Improve Cognitive Screening and Assessment for Clinical and Research Advancement

Abstract

Alzheimer’s disease (AD) is the only cause of death ranked in the top ten globally without precise early diagnosis or effective means of prevention or treatment. Further, AD was identified as a pandemic [1] well before COVID-19 was dubbed a 21st century pandemic [2]. And now, with the realization of the prominent secondary impacts of pandemics, there is a growing, widespread recognition of the tremendous magnitude of the impending burden from AD in an aging world population in the coming decades [3]. This appreciation has amplified the growing and pressing need for a new, efficacious, and practical platform to detect and track cognitive decline, beginning in the preliminary (prodromal) phases of the disease, sensitively, accurately, effectively, reliably, efficiently, and remotely [4–7]. Moreover, the parallel necessity of clarifying and understanding risk factors, developing successful prevention strategies [8–17], and discovering and monitoring viable and effective treatments could all benefit from accurate and efficient screening and assessment platforms. Modern recognition of AD [18] as a common affliction of the elderly began in 1968 with a paper by Blessed, Tomlinson, & Roth [19] in which two tests, one a brief assessment of cognitive function and the other a measure of daily function, demonstrated impairment which was associated with the postmortem counts of neurofibrillary tangles, composed mainly of microtubule-associated protein-tau (tau), in the brain, though not to senile plaques, composed mainly of amyloid-β (Aβ). Even in more recent analyses, the tangles correspond with the severity of dementia more than the plaques [20, 21] Since 1960, a plethora of cognitive tests, paper and pencil [22, 23], simple screening models [24], and computerized [25–27], have been developed to assess the dysfunction associated with AD. However, there has been limited application of Modern Test Theory, which includes Item Characteristic Curve Analysis, used in the technological development of such tools [28–31], along with widespread failure to understand the underlying AD pathological process to guide test development [32, 33]. The lack of such development has likely been a major contributor to the failure of the field to develop timely screening approaches for AD [34, 35], inaccurate assessment of the progression of AD [36], and even now, failure to find an effective approach to stopping AD.

Correctness and response time distributions in the MemTrax continuous recognition task: Analysis of strategies and a reverse-exponential model

“…The precision provided by MemTrax also suggests that MemTrax could improve the specification of the severity of cognitive impairment in early phases of AD ( Ashford et al, 1995 , Ashford et al, 2019a ; Ashford and Schmitt, 2001 ; Ashford, 2008 ), as well as the pace of change over time with repeat testing. By assessing performance metrics and RT, MemTrax also has the capability to screen for many varieties of cognitive impairment and would be an ideal tool for use in the elderly US population for the Medicare Annual Wellness Visit ( Ashford et al, 2022 ). However, more testing in clinical populations is needed to implement on-line testing for broad clinical applicability and widespread screening.…”

“…Currently, there is a significant and recognized lack of adequate instruments for brief cognitive screening and early detection of the dementia caused by AD ( Ashford, 2008 ; De Roeck et al, 2019 ; Ashford et al, 2022 ). Most tools for assessing cognitive function require face-to-face administration using paper-and-pencil instruments, which are complex, labor-intensive, and subject to intra-rater and inter-rater variability.…”

Amyloid PET: A Questionable Single Primary Surrogate Efficacy Measure on Alzheimer Immunotherapy Trials

“…We are not in a position to point to any specific reasons as to why the amyloid hypothesis has failed so far [ 19 ]. We, however, have noted its paradoxical survival for well over 30 years without any proof of its validity and despite multiple indications on the contrary, including the many failed treatment attempts, which should be clear evidence to move in new directions in the search for effective treatments [ 20 ].…”

Auditory Biases in Cognitive Assessment: Insights from a Hearing-Loss Simulation for the Screening of Dementia due to Alzheimer’s Disease

“…In conclusion, it is hoped this study will help raising awareness amongst clinicians and researchers of the existence of sensory biases in cognitive assessment [17,36] and may contribute to improving clinical screening and assessment tools [44]. Absolute thresholds (in dB Hearing Level, HL) for the average 70-year-old (HL70yrs) and 85year-old (HL85yrs), as used for the input to the hearing-loss simulator.…”