Assessing the severity of Alzheimer's disease in your patients

Alzheimer's disease is a progressive, neurological disease with mild, moderate, and severe stages. Each stage of Alzheimer's disease is associated with distinct clinical features and symptoms, usually measured by cognitive and functional losses. Patients may progress through each of the stages over several years.

The cognitive deficits are usually seen first. Patients may conceal these deficits, however, and family, friends, and colleagues may ignore the evidence for some time. As the disease progresses, the cognitive losses increase and are accompanied by functional losses apparent in the increasingly reduced ability of the patient with Alzheimer's disease to maintain normal activities of daily living (ADLs), including grooming, toileting, and eating.

Assessment scales can be used to identify and evaluate cognitive and functional deficits in patients with Alzheimer's disease. Almost 60% of patients diagnosed with Alzheimer's disease are already in the moderate to severe stage. The modified Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory (ADCS–ADL19) is particularly beneficial for these patients.

Parameters measured in the ADCS–ADL19

• Eating
• Obtaining a beverage
• Walking
• Toileting
• Bathing
• Grooming
• Dressing
• Using the Telephone
• Watching Television
• Attending to conversation
• Clearing dishes after meal/snack
• Misplacing/losing items
• Disposing of garbage appropriately
• Traveling outside of home
• Being left alone
• Turning on faucets
• Turning off faucets
• Turning on lights
• Turning off lights

All parameters are evaluated for the 4 weeks preceding the interview, and scoring ranges from 0 (total disability) to 54 (total independence).

Effects of NAMENDA monotherapy in moderate to severe Alzheimer's disease

Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, for the Memantine Study Group. Memantine in moderate to severe Alzheimer's disease. N Engl J Med. 2003;348:1333-1341.

Study overview. The effects of NAMENDA monotherapy on cognition and functional ability were assessed in patients with moderate-to-severe Alzheimer's disease in this randomized, multicenter, double-blind, parallel-group, placebo-controlled U.S. study. A total of 252 patients aged = 50 years with a MMSE* score of = 3 to = 14 points were randomized to receive either NAMENDA 10 mg BID (n=126) or placebo BID (n=126) for 28 weeks.

Findings. Seventy-one patients discontinued treatment prematurely—29 (23%) receiving NAMENDA and 42 (33%) receiving placebo. A significantly greater therapeutic effect was observed in the NAMENDA group compared to the placebo group with respect to both cognition, as measured by the CIBIC-Plus* and SIB* scales, and functional ability, as measured by the ADCS-ADL19* scale for OC analysis only (p = 0.064 for CIBIC + with LOCF analysis).

First Combination Therapy Trial in moderate to severe Alzheimer's disease

Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer's disease already receiving donepezil: A randomized controlled trial. JAMA. 2004;291:317-324.

Study overview. The benefits of NAMENDA in combination with donepezil were assessed in a randomized, multicenter, double-blind, parallel-group, placebo-controlled U.S. study in patients with moderate-to-severe Alzheimer's disease. The study involved 404 outpatients aged = 50 years with a MMSE* score of = 5 to = 14 points, who had already been taking donepezil for at least 6 months. Patients were randomized to receive treatment with NAMENDA 10 mg BID plus donepezil 5 mg or 10 mg QD, or donepezil 5 mg or 10 mg QD plus placebo BID for 24 weeks.

Findings. A significantly greater therapeutic effect was observed in the NAMENDA plus donepezil group, compared with the donepezil plus placebo group. Patients receiving combination therapy with NAMENDA plus donepezil demonstrated significantly less decline in cognitive ability, as measured by the SIB* and CIBIC-Plus* scales, compared with patients receiving donepezil plus placebo. Patients receiving combination therapy with NAMENDA plus donepezil also demonstrated significantly less decline in functional ability, as measured by the ADCS-ADL19* scale. In addition, patients receiving NAMENDA plus donepezil were significantly more likely to stay on therapy and complete the trial than patients receiving donepezil plus placebo.

NAMENDA in severe dementia

Winblad B, Poritis N. Memantine in severe dementia: Results of the 9M-Best Study (Benefit and Efficacy in Severely Demented Patients During Treatment with Memantine). Int J Geriatr Psychiatry. 1999;14:135-146.

Study overview. A total of 166 nursing home patients with a diagnosis of severe dementia—either Alzheimer's disease (n=79) or vascular dementia (n=87)—were randomized to receive NAMENDA 10 mg/day or placebo for 12 weeks.

Findings. Significantly greater functional improvement was observed in the NAMENDA group compared with the placebo group. The results of the BGP* “care dependence” subscale demonstrated a 3.1-point improvement in patients receiving NAMENDA and a 1.1-point improvement in those receiving placebo. A positive response, as measured by the CGI-C*, was seen in 60 patients (73%) receiving NAMENDA and 38 patients (45%) receiving placebo. These findings indicate that in severely demented patients, treatment with NAMENDA leads to functional improvement and reduces dependence.

* MMSE=Mini-Mental State Examination; CIBIC-Plus=Clinician's Interview-Based Impression of Change Plus Caregiver Input; SIB=Severe Impairment Battery; ADCS-ADL19=Alzheimer's Disease Cooperative Study - Activities of Daily Living19; BGP=Behavioral Rating Scale for Geriatric Patients; CGI-C=Clinical Global Impression of Change.