Restricted accessEditorialFirst published online 2025-1
The importance of non-pharmacological interventions to improve cognitive reserve prior to the administration of a drug against the causative agent of Alzheimer's disease
Lecanemab, an antibody drug targeting amyloid-β, has been approved to treat Alzheimer's disease (AD) in the United States and Japan recently. However, there are several concerns about Lecanemab, such as its minimum biological effects, possible side effects, and its economic burden. On the other hand, non-pharmacological approach without major side effects has a potential to alleviate the symptoms of AD by improving cognitive reserve, which is individual's resilience to AD pathology. It is important to compare the benefits and risks of pharmacological and non-pharmacological approaches, especially in the oldest old with AD, to give priority to the safe and cost-effective approach.
van der FlierWMde VugtMESmetsEMA, et al.Towards a future where Alzheimer's disease pathology is stopped before the onset of dementia. Nat Aging2023; 3: 494–505.
5.
JansenWJOssenkoppeleRKnolDL, et al.Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA2015; 313: 1924–1938.
JamesBDBennettDABoylePA, et al.Dementia from Alzheimer disease and mixed pathologies in the oldest old. JAMA2012; 307: 1798–1800.
8.
ChuiHCRamirez-GomezL. Clinical and imaging features of mixed Alzheimer and vascular pathologies. Alzheimers Res Ther2015; 7: 21.
9.
BennettDA. Mixed pathologies and neural reserve: implications of complexity for Alzheimer disease drug discovery. PLoS Med2017; 14: e1002256.
10.
SternYArenaza-UrquijoEMBartres-FazD, et al.Whitepaper: defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement2020; 16: 1305–1311.
11.
SnowdonDANunS. Healthy aging and dementia: findings from the Nun Study. Ann Intern Med2003; 139: 450–454.
12.
SternYBarnesCAGradyC, et al.Brain reserve, cognitive reserve, compensation, and maintenance: operationalization, validity, and mechanisms of cognitive resilience. Neurobiol Aging2019; 83: 124–129.
13.
PettigrewCSoldanA. Defining cognitive reserve and implications for cognitive aging. Curr Neurol Neurosci Rep2019; 19: 1.
14.
SternY. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol2012; 11: 1006–1012.
15.
RoeCMMintunMAD’AngeloG, et al.Alzheimer disease and cognitive reserve: variation of education effect with carbon 11-labeled Pittsburgh compound B uptake. Arch Neurol2008; 65: 1467–1471.
16.
KemppainenNMAaltoSKarraschM, et al.Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol2008; 63: 112–118.
17.
RentzDMLocascioJJBeckerJA, et al.Cognition, reserve, and amyloid deposition in normal aging. Ann Neurol2010; 67: 353–364.
18.
RabinJSKleinHKirnDR, et al.Associations of physical activity and β-amyloid with longitudinal cognition and neurodegeneration in clinically normal older adults. JAMA Neurol2019; 76: 1203–1210.
19.
SohnBKByunMSYiD, et al.Late-life physical activities moderate the relationship of amyloid-beta pathology with neurodegeneration in individuals without dementia. J Alzheimers Dis2022; 86: 441–450.
20.
QuerbesOAubryFParienteJ, et al.Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve. Brain2009; 132: 2036–2047.
21.
MortamaisMPortetFBrickmanAM, et al.Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia. Am J Geriatr Psychiatry2014; 22: 1336–1345.
22.
BehfarQRichterNKuralM, et al.Improved connectivity and cognition due to cognitive stimulation in Alzheimer's disease. Front Aging Neurosci2023; 15: 1140975.
23.
WoodsBRaiHKElliottE, et al.Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database Syst Rev2012; 2: CD005562.
24.
SommerladAKivimakiMLarsonEB, et al.Social participation and risk of developing dementia. Nat Aging2023; 3: 532–545.
