# Calibrating Mini-Mental State Examination Scores to Predict Misdiagnosed Dementia Patients
## 1 Introduction  
There are more than 8.7 million people across Europe living with dementia (Mapping-dementia-friendly-communities-across-europe [[https://ece.europa.eu/eip/ageing/library/mapping-dementia-friendly-communities-across-europe_en.html](https://ece.europa.eu/eip/ageing/library/mapping-dementia-friendly-communities-across-europe_en.html)]([https://ece.europa.eu/eip/ageing/library/mapping-dementia-friendly-communities-across-europe_en.html](https://ece.europa.eu/eip/ageing/library/mapping-dementia-friendly-communities-across-europe_en.html)) (accessed on 28 July 2021)). With an ageing population and no effective treatment, this number is set to rise to 152 million globally by 2050 (Dementia-number-of-people-affected-to-triple-in-next-30-years [[https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years](https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years)]([https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years](https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years)) (accessed on 28 July 2021)), highlighting the huge unmet need for better managing this condition [1]. The sheer number of people living with the disease and the direct and indirect costs of providing care and support for them have made dementia quite challenging. The Alzheimer's disease (AD) and the other neurodegenerative causes of late-life dementia have become one of the greatest medical challenges of our time. Diagnosis is quite challenging; it can be difficult to make and in a significant proportion of cases will be inaccurate. It is common for a diagnosis to be delayed for 2-3 years after symptom onset [2], and the presence of AD pathology will, on average, prove to be mistaken at postmortem examination, in as many as 25% of cases [3]. Currently, there are no licensed treatments that will stop, let alone reverse, the progression of the neurodegenerative pathologies. In recent years, however, understanding aspects of the biological and clinical characteristics of dementias has benefited from the ability to interrogate the increasing quantities of electronic data that exist for this growing patient population. One example concerns the delineation of the typical pattern of response to one of the symptomatic treatments (cholinesteraseerase inhibitors) that are licensed for the treatment of AD, using clinical evaluations recorded in thousands of electronic patient records. These evaluations included a summary estimate of a patient's cognitive ability in the form of a score (out of 30) on a bedside or office-based cognitive test such as the Mini-Mental State Examination (MMSE) [4] or the Montreal Cognitive Assessment (MoCA) [5]. Given the progressive nature of AD, it can be assumed that the score achieved by a given patient will remain unchanged for a variable length of time after the diagnosis has been made, and then gradually worsen. When the latter occurs, the score obtained at time \(t\) will usually be lower than the score at time \(t-1\). Other than in patients who enjoy a particularly strong therapeutic effect from cognitively-enhancing drugs such as acetylcholinesterase inhibitors [6], it is almost never the case that a patient's score on the MMSE undergoes a significant increase between two assessments. Moreover, the longer the interval between assessments, it is negative change rather than stability that is the expected pattern of change. [PERSON] et al. [7] found that, other than in patients who started with MMSE scores of 10 or less, the improvement in MMSE score after starting a cholinesterase inhibitor seldom exceeded 5 points, and that the trajectory returned to progressive decline after as little as six months of treatment.