A qualitative analysis of the mini mental state examination on Alzheimer's disease patients treated with cholinesterase inhibitors

Indications:24 patients with Alzheimer's disease.Patients:99 patients, 71 female and 28 male, age was 77.7 ± 6.1 years. Nonresponders (NR): n=38, 27 female and 11 male, age was 78.4 ± 4.0 years. Responders (R): n=61, 44 female and 17 male, age was 77.3 ± 7.1 years. Exelon: n=24; NR: n=9, R: n=15. Donepezil: n=70; NR: n=26, R: n=44. Galantamine: n=5; NR: n=3, R:n=2. Follow up: 3 and 9 months.TypeofStudy:Clinical study designed to evaluate whether there is a specific pattern of cognitive improvement in a population of Alzheimer's disease (AD) patients treated with cholinesterase inhibitors (ChEIs: Exelon, donepezil or galantamine) by a qualitative analysis of the Mini-Mental State Examination (MMSE). CRONOS project.DosageDuration:Dosage not stated. Duration: 9 months.ComparativeDrug:Donezepil in 70 patients and galantamine in 5 patients. Dosage not stated, duration 9 months.Results:15/24 Exelon patients, 44/70 donezepil patients and 2/5 galantamine patients were classified as R after 9 months of treatment. Further results are given for the whole group of patients without separate data for Exelon. At the 3rd month, only the MMSE score was significantly higher among the responders (21.5 versus 18.5), while at the 9th month, both the MMSE score (21.8 versus 15.8) was higher and the functions lost at the ADL (1.1 versus 1.9) and IADL (4.2 versus 5.2) were lower. The most severely affected MMSE domain at baseline was delayed recall, followed by copying a design, attention and temporal orientation. During the first 3 months, NR patients significantly worsened their scores in the following items: temporal orientation (-0.42 points), spatial orientation (-0.26 points) and delayed recall (-0.42 points) with respect to the R group (0.21, 0.34, 0.26, respectively). These findings could be seen as due to a possible pharmacological effect on these specific domains (orientation and memory) in the short run. After 9 months, the differences between the 2 groups were observed also for registration (p < 0.001), attention (p ≤ 0.0005), obeying oral commands (p < 0.0005), reading and obeying commands (p ≤ 0.0005), writing a sentence (p ≤ 0.0005) and copying a design (p ≤ 0.05). Only the domains denomination and sentence repetition did not differ between R and NR. Among the 11 items investigated, those that had an independent effect on the change of MMSE at the 9th month, were: temporal orientation (b = 0.66), spatial orientation (b = 1.43), delayed recall (b = 1.67), obeying an oral command (b = 1.73) and reading and obeying command (b = 1.86). Hence, the item with more relevant impact on the change at the 9th month is reading and obeying command, with an average increase of 1.86 points respect to a unit increase on the change at the 3rd month.AdverseEffects:No adverse events were mentioned.AuthorsConclusions:Our findings show that the ChEI treatment does not induce equal effect in all subjects; some patients seem to stabilize or increase their global cognitive performance after 9 months, while others seem not to benefit from the treatment. The qualitative analysis of the MMSE to evaluate the pharmacological response could give useful information both to better understand the characteristics of subjects with different responses and to quantify the ChEl effect on the cognitive performance. Our findings suggest that the improvement induced by the drug on the MMSE can be seen, in a short run, on selected item such as memory and orientation. On the long run, most of the item result to be changed and only a long-term follow up could give some indication on the stability of these increased conditions.FreeText:The patient evaluation consisted of a brief interview to the caregiver, a clinical visit, and a multidimensional assessment. months from the enrollment. The data recorded were: demographic characteristics, cognitive status: administration of the MMSE at baseline and at every follow-up; functional status: proxy evaluation of the independence in the activities of daily living (ADL) and the instrumental activities of daily living (IADL) at baseline and every follow-up; somatic health status: revision of clinical records, if any, and proxy referral about the presence of chronic diseases potentially contraindicating a ChEls treatment ; previous or current use of medications active on the central nervous system. Use of ChEls was registered both in terms of type and dosage. Both at the first visit and at the follow-ups, physicians were set free to continue previous ChEls treatment, adjust pharmacological regimens, or prescribe a new drug. At the end of each visit, the patient was given the exact quantity of ChEls drug until the next follow-up. The MMSE score has been analyzed both as a total score (range: 0-30) and a disaggregated score, as follows: temporal orientation (range: 0-5), spatial orientation (range: 0-5), registration (range: 0-3), attention (range: 0-5), delayed recall (range: 0-3), denomination (range: 0-2), sentence repetition (range: 0-1), obeying oral command (range: 0-3), reading and obeying command (range: 0-1), writing a sentence (range: 0-1), and copying a design (range: 0-1). Variations of the MMSE score have been computed as follows: Change at 3rd month = score at 3rd month - score at baseline; change at 9th month = score at 9th month - score at baseline. Therefore, positive values indicate increases in the performance at follow ups. All patients who lost one or more points have been labeled as non-responders (NR), whereas all patients who gained zero or more points have been labeled as responders (R).