The purpose of this study was to investigate the clinical and caregivers impression of Aricept ® treatment in patients suffering from Multi-Infarct Dementia (MID).
In a prospective study 73 MID patients1 were treated with Donepezil (Aricept®) for 16-to 20-weeks. Donepezil was administered as a 5mg tablet once daily at bedtime. After four weeks, patients tolerant of the 5-mg dose were increased to 10 mg daily. All patients satisfied the DSM-III-R criteria for Multi-Infarct Dementia.2After 16-to 20-weeks of treatment, the patient's caregiver completed a questionnaire concerning the effectiveness of the drug. Subjective cognitive improvement, MMSE,3 ADL4 and IADL5 outcomes were all assessed before and after treatment (referred to as Clinical Impression). Behavioral outcomes evaluated included depression, agitation, violence, anxiety, and paranoid thoughts. Functional and overall family satisfaction were also evaluated. Side effects as well as reasons for discontinuation from the study were also reported.
Seventy-three patients participated in the study. Twelve patients (16 percent) terminated participation due to side effects. Total adverse events were reported in 34 (46.5 percent) of patients. Cognitive improvement was reported in 31 (42.4 percent) patients. Verbal skills and attention were the most commonly reported cognitive improvement. Average MMSE declined by 2.6 points after 16-weeks of treatment. No behavioral improvement was reported. Behavioral deterioration was reported in 16 (21.9 percent) of patients. Functional improvement was reported in 32 (42.8 percent) patients. Overall positive family satisfaction was reported in 54 (73.9 percent) patients.
Although Donepezil treatment was approved by the FDA for the treatment of Alzheimer's Disease (AD), such treatment for MID patients appears to be a reasonably safe and effective treatment from the caregiver and family's point of view.
References
1.
Katzman R : Alzheimer's Disease: N Engl J Med. 1986; 314: 964-964.
2.
American Psychiatric Association , Committee on Nomenclature and Statistics: Diagnosis and statistical manual of mental disorders, Ed 3, Revised. Washington, DC, American Psych Assoc. 1987, p 121-121.
3.
Folstein MF , Folstein S, McHugh PR: Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psych Res. 1975; 12: 189-198.
4.
Katz S : Assessing self maintenance; Activity of daily living, mobility, and instrumental activity of daily living. J Am Geriatr Soc. 1983; 31: 721-727.
5.
Lawton MP : Scale to measure competence in everyday activities. Psychopharm Bull. 1988; 24(4): 609-613.
6.
Erkinjuntti T : Multi-infarct dementia: Clinical features and diagnosis. Geriatric Medicine Today. 1990; 9: 22-40.
7.
Hachinski V , Lassen N, Marshall J: Multi-infarct dementia: A cause of mental deterioration in the elderly. Lancet. 1974; 207-209.
8.
Wallin A , Blennow K: Heterogeneity of vascular dementia: Mechanisms and subgroups. J of Geriatric Psychiatry and Neurology. 1993; 6: 177-188.
9.
Tomlinson B , Blessed G, Roth M: Observations on the brains of demented old people. J Neurol Sci. 1970; 11: 205-242.
10.
Reuben DB , Yoshikawa TT, Besdine RW: Supplement Geriatrics Review Syllabus: A core curriculum in Geriatric Medicine: Geriatric Syndromes: The Dementia: 1993-1994: Am Geriatric Soc (AGS).58s-58s.
11.
Loeb C , Gandolfo C: Diagnostic Evaluation of Degenerative and Vascular Dementia. September 1983: Stroke: Vol.14: No. 3: 399-401.
12.
Rogers SL , Doody R, Mohs R, Friedhoff LT: E2020 produces both clinical global and cognitive test improvement in patients with mild to moderately severe Alzheimer's disease: Results of a 30-week phase III trial (abstract). Neurology. 1996; 46: 217-217.
13.
Rogers SL , Friedhoff LT, Apter JT, et al: The efficacy and safety of Donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial. Dementia. 1996; 7: 293-303.
14.
Rogers SL , Friedhoff LT: Donepezil (E2020) produces long-term clinical improvement in Alzheimer's disease. Presented at the 4th International Nice/Springfield Symposium on Advances in Alzheimer's Therapy, April 10-14, 1996.
15.
Aricept® (Donepezil Hydrochloride) Package Insert. Eisai Inc. and Pfizer US Pharmaceuticals: June 1997.
16.
Spencer MP , Folstein MF. The Mini-Mental State Examination. In: Keller PA, Ritt LG. Innovation in clinical practice: A Source Book. 1985; 4: 305-310.
17.
Folstein MF , Anthony JC, et al: Meaning of cognitive impairment in the elderly. J Am Geriat Soc. 1985; 33(4): 228-235.
18.
Anthony JC , LeResche L, Niaz U, et al: Limits of “Mini-Mental State” as a screening test for dementia and delirium among hospitalized patients. Psych Med. 1982; 12: 397-408.
19.
JA Yesavage , TL Brink, TL Rose, et al: Development and validation of geriatric depression rating scale: Preliminary report. 1983: 17: 27-27.
20.
Shua-Haim JR , Sabo MR, Comsti E, Ross JS: Depression in the elderly: Hospital Medicine. July 1997: 44-58.
21.
Shikh JI , Yesavage JA: Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clin Gerontology. 1986; 5: 170-170.
22.
Katz S , Dowens TD, Cash HR, Progress in development of index of ADL. Int J Heath Services. 1976; 6: 493-508.
23.
Katz S , A measure of primary sociobiologic function. J Gerontol. 1970; 10(1): 20-30.
24.
Lawton MP , Moss M, Fulcomer M, et al: A research and service oriented Multi-Level Assessment Instrument. J Gerontol. 1982; 37: 91-97.
25.
M. Doraiswamy : Current Cholinergic Therapy for Symptoms of Alzheimer's Disease. J of Primary Psychiatry.November 1996; 1-11.
26.
Rabins P, Blacker D, Cohen E: Practice Guideline for the treatment of Patients with Alzheimer's disease and other Dementias of late life. May 1997, Volume 154, Number 5.
27.
Davis KL , Thal LJ, Gamzu ER, et al: Tacrine Collaborative Study Group: A double blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. N Engl J Med. 1992; 327: 1253-1259.
28.
Farlow M , Gracon S, Hershey LA, et al: A controlled trial of tacrine in Alzheimer's disease. JAMA. 1992; 268: 2523-2529.
29.
Knapp MJ , Knopman DS, Solomon PR, et al: A 30-week randomized controlled trial of high dose Tacrine in patients with Alzheimer's disease. JAMA.1994; 271: 985-991.
30.
Forette F , Hoover T, Gracon S, et al: A double-blind, placebocontrolled, enriched population study of tacrine in patients with Alzheimer's disease. Eur J Neurology.1995; 2: 1-10.
31.
Foster NL , Petersen RC, Gracon S, Lewis K: Tacrine 970-6 Study Group: An enriched-population, double blind, placebo controlled, crossover study of tacrine and lecithin in Alzheimer's disease. Dementia. 1996; 7: 260-266.
32.
Lyketsos CG , Corazzini K, Steele CD, Kraus MF: Guidelines for the use of Tacrine in Alzheimer's disease: Clinical application and effectiveness. J Neuropsychiatry Clin Neurosci. 1996; 8: 67-73.
33.
Watkins PB , Zimmerman HJ, Knapp MJ, et al: Hepatotoxic effects of Tacrine administration in patients with Alzheimer's disease. JAMA. 1994; 271: 992-998.
34.
Maning FC : Tacrine Therapy for the Dementia of Alzheimer's Disease. American Family Physician. 1994; 50: 819-823.
35.
Rosen WG , Mohs RC, Davis KL: A new rating scale for Alzheimer's disease. Am J Psychiatry. 1982; 139: 1136-1139.
36.
McKhann G , Drachman D, Folstein M, et al: Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984; 34: 939-944.
37.
Reuben DB , Yoshikawa TT, Besdine RW: Geriatrics Review Syllabus: A core curriculum in Geriatric Medicine: Part I, General Principles of Aging: Demography of Aging: 1996: Am Geriatric Soc (AGS).105-114.
38.
Tabaton M : Research advances in the biology of Alzheimer's disease. Clin Geriat Med. 1994; 10: 249-249.
Evans D , Funkenstein H, Albert M, et al: Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA. 1989; 262: 2551-2556.
41.
Butler R , Ahronheim J: Vascular dementia: Stroke prevention takes on new urgency. A roundtable discussion: Part 1. Geriatrics. 1993; 48(11): 32-42.
42.
Skoog I , Nilsson L, et al: A population-based study of dementia in 85-year-olds. N Engl J Med. 1993; 328: 153-158.
43.
Holstein J , Chatellier G: Prevalence of associated diseases in different types of dementia among elderly institutionalized patients: Analysis of 3,447 records. JAGS. 1994; 42: 972-977.
Larson E : Illnesses causing dementia in the very elderly. N Engl J Med. 1993; 328: 203-205.
46.
Meiran N , Stuss D, et al: Diagnosis of dementia: Methods of interpretation of scores of 5 neuropsychological tests. Arch Neurol. 1996; 53: 1043-1054.
47.
Butler R , Ahronheim J, et al: Vascular dementia: how to make the diagnosis in office practice. A roundtable discussion: Part 2. Geriatrics. 1993; 48(12): 39-47.
48.
Bergethon P , Sabin T: The P300 and vascular dementia: Not quite ready for prime time. J Am Geriatr Soc. 1995; 43: 1311-1313.
Inzitari P.Ital J : Hachinski's ischemic score and the diagnosis of vascular dementia: A review. Neurol Sci. 1993; 14: 539-546.
51.
Potter J , Ranno A: Prevalence and treatment of vascular dementia. Clinical Geriatrics. 1995; 3: 51-59.
52.
Rosen WG , Terry RD, Katzman R: Pathological verification of ischemic score in differentiation of dementia. American Journal Neurology. 1980: Vol.7: 486-488.
53.
Chui H , Victoroff J: Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers. Neurology. 1992; 42: 473-480.
54.
Lopez O : Reliability of NINCDS-AIREN clinical criteria for the diagnosis of vascular dementia. Neurology. 1994; 44: 1240-1245.
55.
Butler R , Ahronheim J, et al: Vascular dementia: An updated approach to patient management. A roundtable discussion: Part 3. Geriatrics. 1993; 49(1): 39-46.
56.
Tatemichi T , Desmond D: Dementia after stroke: Baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology. 1992; 42: 1185-1193.
57.
Komnen E , Offord K, Ozaki H: A clinical and autopsy study of dementia in Olmstead county, Minnesota 1980-1981. Neurology. 1987; 37: 426-430.
58.
De Reuck J , Sieben G: Dementia and confusional state in patients with cerebral infarcts. Eur Neurol. 1982; 21: 94-97.
59.
Kotila M , Waltimo O: Dementia after stroke. Eur Neurol. 1986; 134-140.
60.
Cummings J , Miller B, et al: Neuropsychiatric aspects of multiinfarct dementia and dementia of the Alzheimer type. Arch Neurol. 1987; 44: 389-393.
Reding M , Haycox J, Blass J: Depression in patients referred to a dementia clinic. A three year prospective study. Arch Neurol. 1985; 42: 894-896.
63.
Hachinski V : Preventable senility: a call for action against the vascular dementias. Lancet. 1992; 340: 645-648.
64.
Durtsman R , Ruhling R, et al: Aerobic exercise training and improved neuropsychological function of older individuals. Neurobiol Aging. 1984; 5: 35-42.
65.
Meyer J , Judd B, et al: Improved cognition after control of risk factors for multi-infarct dementia. JAMA. 1986; 256: 2203-2209.
66.
Mortel PM , Wood S: Prospective studies of cerebral perfusion and cognitive testing among elderly normal volunteers and patients with ischemic vascular dementia and Alzheimer's Disease. Angiography. 1994; 45: 171-180.
67.
Meyer S , Judd B: Improved Cognition after control of risk factors for Multi Infarct Dementia. JAMA. 1986; 256: 2203-2209.
68.
National High Blood Pressure Education Program Working Group . Hypertension. 1994; 23: 275-275.
69.
The Fifth Report of the Joint national Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V) . Arch Intern Med. 1993; 153: 154-154.
70.
Rothrock J , Hart R: Antithrombolytic therapy in cerebrovascular disease. Ann Intern Med. 1991; 115: 885-895.
71.
Meyer J , Rogers R, McClintic K, et al: Randomized clinical trials of daily aspirin therapy in Multi Infarct Dementia. A pilot study. J Am Geriatr Soc. 1989; 37: 549-549.
72.
The Boston Area Trial for Atrial Fibrillation investigators . The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990; 323: 1505-1511.
73.
Falkeborn M , Person I, Terent A, et al: Hormone replacement therapy and the risk of stroke. Follow up a population based cohort in Sweden. Arch Intern Med. 1993; 153: 1201-1201.
74.
Morris J : Classification of dementia and Alzheimer's disease. Acta Neurol Scand. 1996; suppl. 165: 41-50.
75.
Shua-Haim JR , Comsti E, Ross JS: Donepezil (Aricept ®): The caregivers voice and clinical impression: Am. J. Alzheimer's Disease. 1997; 12: 272-279.
