Vitality, Medicine & Engineering Journal

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Mathieu Maltais


Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, 37 allée Jules Guesdes, 31000 Toulouse, France ;
Corresponding Author: Mathieu Maltais, PhD, Gérontopôle de Toulouse, Institut du Vieillissement, Bâtiment B, 37 Allée Jules Guesde, 31000, Toulouse France, +33 6 74 70 63 71, E-mail :

Care Weekly 2019;
Published online April  9, 2019,



Frailty is a multidimensional condition that makes older adults more vulnerable to adverse health events such as disability, hospitalizations and death (1, 2). The multidimensional (1) aspect of frailty makes it difficult to pinpoint its origins, but somehow cross-sectional studies have found that brain health is more deteriorated in frail individuals (3, 4). Research is now focused in finding biomarkers that are related to adverse events in older adults (5), thus raising the importance that brain health biomarkers, such as amyloid load and white matter lesions, could be associated with frailty severity.
Up to now, only cross-sectional studies have found that different markers of cerebral damage were found to be associated with frailty: 1) frail individuals were found to have higher amyloid load compared to non-frail individuals (4) and 2) frail older adults had more white matter lesions (3). Accordingly, two studies that used ancillary data from the Multidomain Alzheimer’s Preventive Trial (MAPT) (6) study have found interesting results regarding the prospective associations between brain health and frailty. The first study which used the magnetic resonance imaging (MRI) data for the detection of white matter lesion has found that older adults with higher white matter lesions had a 6% likelihood of increasing their frailty phenotype score by 1 point after 3 years (7). White matter lesions can affect motor function and gait speed, thus increasing frailty severity risks.
In line with this, another study using positron emission tomography (PET) scans for the acquisition of brain amyloid load have found prospective and positive associations with a 19-item frailty index that used only items that were not directly linked to cognition. More specifically, this study found that brain regions, such as the putamen regions (anterior and posterior) and the precuneus regions were all associated with increased frailty after 3 years (8).
Higher amyloid load in specific regions such as the putamen and the precuneus play a role in coordination and motor function (9, 10). Finally, these studies point to the fact that the development of frailty can be promoted if the speed of accumulation of amyloid load and white matter lesions is accelerating. As such, during this stage, prevention strategies should be implemented to prevent the precocious appearance of frailty and maintain dependence in this population. Interestingly, a recent study from Buchman and colleagues (11) have shown that high levels of physical activity is associated with better function and cognition, independently of other brain pathologies. Thus, slowing down frailty could slow down Alzheimer’s Disease (AD) pathology.
These studies add to the body of literature that frailty and AD pathology are both tightly associated and that one condition probably does not go without the other (12). In line with this, a recent and interesting study from Wallace et al (13) found that frailty status can modify the association with Alzheimer’s Disease, increasing the potential influence of frailty in cognitive disorders. Finally, the recent contributions from our group (7, 8) and others (11, 13) are important contributions in this field, but future studies are needed to try and tease out the direction of the association between brain health and frailty. An observational study using a longer follow-up with many time-point measurements of brain imaging could be of importance by improving the precision of the trajectory for both outcomes.



1.    Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. PubMed PMID: 23395245; PubMed Central PMCID: PMCPMC4098658.
2.    Rockwood K, Howlett SE, MacKnight C, et al. Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Gerontol A Biol Sci Med Sci. 2004 Dec;59(12):1310-7. PubMed PMID: 15699531.
3.    Avila-Funes JA, Pelletier A, Meillon C, et al. Vascular Cerebral Damage in Frail Older Adults: The AMImage Study. J Gerontol A Biol Sci Med Sci. 2017 Jul 1;72(7):971-977. doi: 10.1093/gerona/glw347. PubMed PMID: 28329104; eng.
4.    Yoon DH, Lee JY, Shin SA, et al. Physical Frailty and Amyloid-beta Deposits in the Brains of Older Adults with Cognitive Frailty. Journal of clinical medicine. 2018 Jul 9;7(7). doi: 10.3390/jcm7070169. PubMed PMID: 29987248; PubMed Central PMCID: PMCPMC6068928. eng.
5.    Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature. 2018 2018/09/01;561(7721):45-56. doi: 10.1038/s41586-018-0457-8.
6.    Vellas B, Carrie I, Gillette-Guyonnet S, et al. Mapt Study: A Multidomain Approach for Preventing Alzheimer’s Disease: Design and Baseline Data. J Prev Alzheimers Dis. 2014 Jun;1(1):13-22. PubMed PMID: 26594639; PubMed Central PMCID: PMCPMC4652787.
7.    Maltais M, de Souto Barreto P, Moon SY, et al. Prospective association of white matter hyperintensity volume and frailty in older adults. Exp Gerontol. 2019 Jan 10;118:51-54. doi: 10.1016/j.exger.2019.01.007. PubMed PMID: 30639444.
8.    Maltais M, de Souto Barreto P, Hooper C, et al. Association between brain -amyloid and frailty in older adults. J Gerontol A Biol Sci Med Sci. 2019 Jan 9. doi: 10.1093/gerona/glz009. PubMed PMID: 30629123.
9.    Cham R, Perera S, Studenski SA, et al. Striatal dopamine denervation and sensory integration for balance in middle-aged and older adults. Gait & posture. 2007 Oct;26(4):516-25. doi: 10.1016/j.gaitpost.2006.11.204. PubMed PMID: 17196819; eng.
10.    Margulies DS, Vincent JL, Kelly C, et al. Precuneus shares intrinsic functional architecture in humans and monkeys. Proceedings of the National Academy of Sciences of the United States of America. 2009 Nov 24;106(47):20069-74. doi: 10.1073/pnas.0905314106. PubMed PMID: 19903877; PubMed Central PMCID: PMCPMC2775700. eng.
11.    Buchman AS, Yu L, Wilson RS, et al. Physical activity, common brain pathologies, and cognition in community-dwelling older adults. Neurology. 2019 Jan 16. doi: 10.1212/wnl.0000000000006954. PubMed PMID: 30651386; eng.
12.    Buchman AS, Schneider JA, Leurgans S, et al. Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology. 2008;71(7):499-504. doi: 10.1212/01.wnl.0000324864.81179.6a.
13.    Wallace LM, Theou O, Godin J, et al. Investigation of frailty as a moderator of the relationship between neuropathology and dementia in Alzheimer’s disease: a cross-sectional analysis of data from the Rush Memory and Aging Project. The Lancet Neurology. 2019;18(2):177-184.