Alzheimer’s Patients May Gain Months of Independent Living With Treatment

A model estimated how long anti-amyloid treatments might extend functional independence for people with early Alzheimer’s disease.

The number of months of independent living an Alzheimer’s patient could expect to gain with anti-amyloid treatment depended on baseline Clinical Dementia Rating Sum of Boxes (CDR-SB) scores and treatment, reported Sarah Hartz, MD, PhD, of Washington University School of Medicine in St. Louis, and co-authors in Alzheimer’s & Dementia. CDR-SB scores range from 0 to 18, with higher scores indicating greater impairment.

For patients with a baseline CDR-SB score of 2, treatment with lecanemab (Leqembi) would extend independence in instrumental activities of daily living (IADLs) — paying bills, driving, remembering medications and appointments, and preparing meals — for 10 months (95% CI 4-18 months), Hartz and colleagues estimated. Treatment with donanemab (Kisunla) in patients with a baseline CDR-SB score of 2 who had low to medium tau would extend independence in IADLs by 13 months (95% CI 6-24 months).

Alzheimer’s patients with a baseline CDR-SB score of 3.5 could expect approximately 4 additional months (95% CI 2-7 months) of independence in IADLs with lecanemab, and 5 additional months (95% CI 2-9 months) with donanemab, the researchers said.

“Our findings give a framework for contextualizing the Clinical Dementia Rating Sum of Boxes score for clinical decision making with disease-modifying treatments of Alzheimer’s disease dementia,” Hartz and co-authors wrote.

The study arose from questions patients had about trial results reported for lecanemab and donanemab, both of which are approved to treat early Alzheimer’s disease. “What people want to know is how long they will be able to live independently, not something abstract like the percent change in decline,” Hartz said in a statement.

“The purpose of this study is not to advocate for or against these medications,” she continued. “The purpose of the paper is to put the impact of these medications into context in ways that can help people make the decisions that are best for themselves and their family members.”

This information can help clinicians and families weigh estimated treatment benefits against risks, the researchers pointed out.

Both lecanemab and donanemab carry serious adverse effects, largely centered around amyloid-related imaging abnormalities (ARIA) with edema or effusion (ARIA-E) or ARIA with microhemorrhages and hemosiderin deposits (ARIA-H). Serious intracerebral hemorrhages and deaths have been reported with this class of drugs.

Hartz and co-authors examined two inflection points on the continuum between independence and dependence in Alzheimer’s disease. The first was the point at which a person could no longer live independently due to an impaired ability to manage IADLs. The second point was when a person could no longer tend to basic activities of daily living (BADL) like personal hygiene.

The researchers studied patients at the Knight Alzheimer Disease Research Center who met eligibility criteria for recent disease-modifying trials, following them for an average of 2.9 years.

All patients were 60 or older at baseline and had global Clinical Dementia Rating (CDR) scores of 0.5 or 1, biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. Global CDR scores range from 0 to 3; a score of 0.5 indicates very mild impairment, and a score of 1 indicates a person is mildly impaired.

Most participants (67%) had very mild (CDR 0.5) Alzheimer’s dementia; the rest had mild Alzheimer’s dementia (CDR 1). The sample included 88% white and 10% Black participants. Overall, 56% were men.

Nearly all participants were independent in BADLs at baseline. Most CDR 0.5 participants (95%) were independent in IADLs, and a minority of CDR 1 participants (40%) were.

For 50% of participants, loss of independence in IADLs occurred when CDR-SB scores exceeded 4.5; loss of independence in BADLs occurred when CDR-SB exceeded 11.5.

Overall, the average annual CDR-SB increase was 1.30 (95% CI 1.13-1.48). Scores on the CDR-SB increased by 1.05/year (95% CI 0.85-1.26) for people with a baseline CDR of 0.5, and by 1.85/year (95% CI 1.70-2.00) for those with a baseline CDR of 1. The researchers estimated the additional years of independence associated with lecanemab or donanemab treatment due to the slower rates of decline in CDR-SB scores reported in clinical trials.

The analysis has several limitations, Hartz and co-authors said. Only patients with biomarker-confirmed Alzheimer’s dementia and longitudinal data were included, potentially limiting the study’s generalizability.

The researchers assumed CDR-SB progression was linear and treatment effects would occur uniformly. In addition, the analysis did not directly investigate loss of function in daily living activities over time, but related the activities to CDR-SB scores.

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