The review was led by Xiaoxia Wei of the Chinese Academy of Medical Sciences and Peking Union Medical College, working with Ruitai Shao, Yves Rolland, Bruno Vellas and Philipe de Souto Barreto, a team anchored at IHU HealthAge in Toulouse, France. The authors conducted a structured PubMed search with a final cutoff of December 31, 2025, and formally appraised study quality using the Newcastle-Ottawa Scale and the Joanna Briggs Institute checklist, finding acceptable methodological quality for most of the included research. Their conclusion is striking in its breadth: Alzheimer’s-related pathology and neurodegeneration appear to have functional correlates beyond cognition, with the pattern of associations varying by biomarker type, by the capacity domain examined and by study design.

To understand why this matters, it helps to unpack the two pillars of the analysis. Intrinsic capacity, a concept championed by the WHO in its 2015 world report on ageing and health, describes the sum total of an individual’s locomotion, cognition, vitality, psychological well-being, hearing and vision. It is increasingly measured as a composite score that predicts disability, hospital admission and mortality. Alzheimer’s biomarkers, meanwhile, now span a well-validated arsenal: amyloid-beta and tau proteins measured in cerebrospinal fluid or blood, neurofilament light chain as a marker of neuronal injury, glial fibrillary acidic protein as a gauge of astrocytic activation, structural MRI to quantify atrophy, and fluorodeoxyglucose positron emission tomography to map the brain’s faltering glucose metabolism. The 2024 revised diagnostic criteria from the Alzheimer’s Association have pushed the field toward defining the disease biologically, which makes the question of what those biology markers do to everyday function increasingly urgent.

The evidence on composite intrinsic capacity scores remains thin, with only two studies addressing it directly, but the longitudinal signals are provocative. Lower intrinsic capacity was associated with elevated plasma p-tau181, a phosphorylated form of tau protein that has become one of the most reliable blood indicators of Alzheimer’s pathology. Higher baseline neurofilament light chain predicted steeper subsequent decline in intrinsic capacity over follow-up, suggesting that ongoing neuronal injury may be a harbinger of global functional deterioration. Notably, the ratio of plasma amyloid-beta 42 to amyloid-beta 40 showed no clear association with composite capacity, hinting that amyloid burden alone may be a weaker predictor of whole-person function than tau and neurodegeneration markers, a hierarchy that mirrors what the field has learned about cognition itself.

Locomotion emerged as one of the most consistently mapped domains, examined in 30 of the included studies. Higher cerebral amyloid-beta deposition was associated with poorer locomotion, especially slower gait speed, more consistently than any other biomarker modality. This finding aligns with a growing body of work showing that gait slowing can precede cognitive decline by several years and that amyloid burden predicts lower extremity performance decline even in cognitively unimpaired older adults. Studies from cohorts including the Atherosclerosis Risk in Communities study and memory clinic populations in Norway linked cerebrospinal fluid amyloid and tau to mobility measures, while imaging work connected regional brain amyloid to gait speed in elderly individuals without dementia. The mechanistic picture is still forming, but the convergence of PET imaging, fluid biomarkers and performance-based measures paints amyloid as a quiet saboteur of movement.

Handgrip strength and vitality, the domain encompassing energy, nutrition and muscle function, told a complementary story. Higher levels of tau biomarkers and neurofilament light chain were more often associated with lower or declining handgrip strength across the reviewed literature. A 12-year cohort study published in The Lancet Healthy Longevity traced blood biomarkers of Alzheimer’s disease against long-term muscle strength trajectories in community-dwelling older adults, and separate analyses found neurofilament light chain elevated in patients with severe sarcopenia and associated with muscle mass and strength in middle-aged and older adults. Neurofilament light chain, which leaks into blood when axons are damaged, appears to function as a shared signal of nervous system wear that registers in the grip of a hand as much as in a memory test.

Depressive symptoms were the most intensively studied non-cognitive domain, appearing in 49 of the 119 studies, and they produced some of the review’s most consistent longitudinal findings. Lower fluid amyloid-beta 42, greater cerebral amyloid deposition and subsequent brain atrophy were all linked to depressive symptoms over time. The relationship runs in both directions conceptually: some studies found that amyloid burden predicted incident depressive symptoms in cognitively normal older adults, while others documented that depressive symptom trajectories tracked with amyloid and cerebral glucose metabolism. Work from the Framingham Heart Study connected midlife depressive symptoms with regional amyloid and tau decades later, and a 2025 study found depressive symptoms correlating with tau accumulation rates in amyloid-positive adults. The authors caution that disentangling depression as prodrome, consequence or comorbidity of Alzheimer’s biology remains one of the field’s thorniest challenges, but the longitudinal consistency of the amyloid and atrophy signals suggests the association is not merely reverse causation or shared vascular risk.

Hearing impairment, examined in 29 studies, was linked mainly to higher tau and neurofilament light chain, reduced glucose metabolism on FDG-PET, and brain atrophy. Longitudinal work showed that age-related hearing loss accelerated cerebrospinal fluid tau levels and brain volume loss, and large imaging analyses associated hearing impairment with smaller total brain volume, temporal lobe volume loss and hippocampal shrinkage. Yet the amyloid story for hearing is muddled: several studies found no link between hearing loss and cerebrospinal fluid amyloid-beta or p-tau181, and at least one reported no influence of hearing loss on brain amyloid at all. This modality-specific divergence matters, because it suggests that different sensory and functional declines may index different arms of the Alzheimer’s pathophysiological cascade, with hearing tracking neurodegeneration more tightly than amyloidosis. Evidence for vision impairment was almost totally absent, with a single study addressing it, a gap the authors flag as a priority for future research.

The review’s implications cut in two directions. Clinically, if biomarkers of Alzheimer’s biology predict declines in gait, grip, mood and hearing, then blood tests that are rapidly entering routine practice could eventually help identify older adults at risk of losing functional independence, not just those at risk of memory loss, and interventions targeting intrinsic capacity could be timed against measurable pathology. Scientifically, the findings reinforce a view of Alzheimer’s as a whole-body, whole-life process rather than a purely cognitive one, echoing the Lancet Commission’s emphasis on dementia prevention across the life course. The authors are careful about limitations: the evidence is largely observational, heterogeneous in design, and heavily weighted toward cross-sectional analyses, with longitudinal data scarce for several domains. Still, with reference centiles for intrinsic capacity now available for monitoring health outcomes in primary care, the prospect of pairing a simple capacity assessment with a blood draw to catch functional decline early is moving from speculative to plausible, and this synthesis provides the evidentiary map for getting there.

Subject of Research: Associations between Alzheimer's disease biomarkers and non-cognitive domains of intrinsic capacity in older adults

Article Title: Alzheimer’s disease biomarkers in relation to non-cognitive domains within the intrinsic capacity framework: a narrative review

Article References: Wei, X., Shao, R., Rolland, Y., Vellas, B., & de Souto Barreto, P. (2026). Alzheimer’s disease biomarkers in relation to non-cognitive domains within the intrinsic capacity framework: a narrative review. GeroScience. https://doi.org/10.1007/s11357-026-02544-w

Image Credits: AI Generated

DOI: 10.1007/s11357-026-02544-w

Keywords: Alzheimer's disease, biomarkers, intrinsic capacity, amyloid-beta, tau protein, neurofilament light chain, GFAP, depressive symptoms, gait speed, hearing impairment, handgrip strength, healthy aging

Intrinsic capacity is a concept that has steadily gained traction in gerontology since the World Health Organization’s Decade of Healthy Ageing placed it at the center of its global strategy. Rather than viewing aging through the narrow lens of disease, intrinsic capacity assembles all of a person’s physical and mental capacities into a single multidimensional construct. In this study, the researchers operationalized it across five distinct domains: mobility, cognition, psychological well-being, sensory function, and vitality. Each domain captures a facet of what an older adult can actually do in daily life, from walking and gripping to remembering, seeing, hearing, maintaining nutrition, and sustaining emotional equilibrium. The central question was deceptively simple: which of these domains matter most when it comes to how older Europeans evaluate their own quality of life, and do those relationships hold equally for men and women, and across the continent’s north-south and east-west divides?

To answer it, the team analyzed longitudinal data from 11,493 adults aged 50 and older who participated in SHARE Waves 5 and 6, covering the years 2013 to 2015. Quality of life was measured using the CASP-12 scale, a validated instrument that assesses four core dimensions of self-reported well-being in later life: control, autonomy, self-realization, and pleasure. The researchers first employed exploratory factor analysis to confirm that the five intrinsic capacity domains genuinely cluster together as a coherent multidimensional construct rather than behaving as isolated traits. They then turned to network analysis, a statistical technique that maps the web of interconnections among variables, to examine how the domains relate to one another and to quality of life, before stratifying results by sex and region to expose hidden disparities.

The statistical architecture of the study is worth appreciating because it reflects a broader shift in how aging research is conducted. Factor analysis served as a gatekeeper, validating that the underlying structure of intrinsic capacity behaved as theorized. Network analysis then went beyond traditional regression by revealing the direct edges between individual indicators and the CASP-12 score, allowing the team to see, for example, that depressive symptoms measured by the European Depression Scale correlated negatively with quality of life at a coefficient of −0.284, while fatigue correlated at −0.324, both highly significant at p below 0.001. These two indicators, nested within the psychological and vitality domains respectively, emerged as the strongest negative correlates of quality of life in the entire network. Cognitive performance and mobility showed weaker but still significant associations, while sensory function played a comparatively modest role.

Over the two-year window between survey waves, the researchers observed a pattern that is both sobering and unsurprising: modest declines in intrinsic capacity paralleled measurable changes in quality of life. The trajectory is important precisely because it is longitudinal. Cross-sectional studies can only show that capacity and well-being travel together at a single moment, leaving open the question of direction. By tracking the same individuals across time, this analysis strengthens the case that deterioration in intrinsic capacity contributes to declining quality of life, and conversely, that preserving capacity may buffer well-being against the inevitable erosion of age. For geriatricians and public health planners, that temporal link is the difference between a correlation worth noting and a lever worth pulling.

Perhaps the most consequential findings concern who bears the greatest burden. Women in the sample exhibited greater deficits in intrinsic capacity and lower quality of life than men, a result consistent with a substantial body of literature documenting the compounding disadvantages that accrue to women over the life course, from higher rates of chronic disease and disability to steeper trajectories of depressive symptoms in old age. Just as striking were the regional patterns. Older adults living in Southern and Eastern Europe showed greater capacity deficits and lower quality of life than their counterparts elsewhere on the continent. The study did not disentangle the full causal web behind these geographic gradients, but the authors frame them within the broader literature on social determinants of health, pointing to differences in income security, health care access, social protection systems, and living arrangements that vary systematically across European welfare regimes.

The regional divide deserves particular scrutiny because it transforms a psychological finding into a political one. If fatigue and depressive symptoms are the strongest correlates of poor quality of life, and if those symptoms cluster disproportionately in regions with weaker social safety nets, then the implication is that mood and energy in old age are not merely private experiences but barometers of policy environments. Pension adequacy, access to mental health services for older adults, community-based support structures, and the availability of preventive care all shape the daily conditions under which intrinsic capacity is maintained or lost. The authors argue explicitly that addressing sex and regional disparities in intrinsic capacity could improve well-being and reduce inequalities across aging populations, an argument that lands with force as European demographics tilt steadily older. Across the continent, the share of people over 65 continues to climb, and the sustainability of health systems will depend increasingly on keeping older adults capable and engaged rather than merely alive.

From an intervention standpoint, the identification of psychological well-being and mobility as priority domains is a call to sharpen existing tools. Depression in later life is chronically underdiagnosed and undertreated, partly because its presentation is often mistaken for a normal feature of aging or masked by physical complaints. The study’s finding that depressive symptoms carry one of the strongest negative associations with quality of life suggests that screening for mood disorders in primary care settings serving older adults, and integrating psychological support into standard geriatric assessment, could yield benefits disproportionate to their cost. Similarly, mobility interventions, from structured physical activity programs to environmental modifications that reduce fall risk and preserve independence, align directly with the second key domain. Fatigue, the single strongest negative correlate at −0.324, is more elusive, but it frequently flags underlying nutritional deficits, anemia, sleep disturbance, or sedentary deconditioning, all of which are modifiable when detected early.

The study is not without limitations, and the authors are careful about the scope of their claims. The data derive from self-reported instruments and span a comparatively short two-year period, and the analysis of secondary data precludes the experimental control needed to establish definitive causation. Yet the sheer scale and geographic breadth of SHARE, together with the methodological rigor of combining factor analysis, network analysis, and stratified comparisons, gives the findings a weight that smaller, single-country studies cannot match. What emerges is a clear and actionable picture of aging in Europe: intrinsic capacity functions as an integrated system whose psychological and mobility components anchor its connection to quality of life, women and residents of Southern and Eastern Europe face systematic disadvantages that demand targeted policy attention, and even modest preservation of capacity over short horizons tracks with better lived experience. As the World Health Organization’s Decade of Healthy Ageing presses toward 2030, this research supplies precisely the kind of evidence needed to move the healthy aging agenda from aspiration to measurement, and from measurement to intervention.

The choice of SHARE as the data backbone of the study merits a brief note for readers unfamiliar with the infrastructure behind such findings. SHARE is a panel survey that interviews the same households repeatedly, harmonizing questions across participating countries so that measures of health, cognition, and economic circumstances remain comparable from Sweden to Spain. That harmonization is what makes a stratified comparison of Northern and Southern Europe statistically meaningful rather than anecdotal, and it explains why the dataset has become a standard resource for cross-national aging research since its first wave in 2004.

The CASP-12 instrument also deserves attention, because it shapes what the study can and cannot say about well-being. Unlike satisfaction measures that ask people to evaluate their lives against a standard, CASP-12 probes whether respondents feel they control their own lives, can act autonomously, pursue self-realization, and experience pleasure. This orientation means the scale is sensitive to the everyday capacities that intrinsic capacity frameworks aim to capture, which may partly explain why psychological and mobility indicators register such clear associations with the score.

The network-analytic approach used by the authors reflects a methodological trend worth understanding. Rather than treating latent constructs as causes of observed symptoms, network models depict symptoms and capacities as mutually reinforcing elements of a system. In such a view, fatigue can erode activity, reduced activity can deepen low mood, and low mood can further drain energy, creating feedback loops that a single regression coefficient would obscure. The correlations reported here, such as the negative links between depressive symptoms and quality of life, are best read as edges in that system rather than isolated effects.

Finally, the two-year horizon of the analysis is both a strength and a boundary on interpretation. Short intervals capture change before cohort effects and survivorship distort the sample, yet they cannot speak to how capacity and quality of life co-evolve over decades. Longer panel follow-up will be needed to test whether early deficits in psychological well-being foreshadow steeper declines later in life.

Subject of Research: The relationship between intrinsic capacity domains and two-year changes in quality of life among older Europeans, including sex and regional differences, analyzed using SHARE data

Article Title: Intrinsic capacity and changes in quality of life among older Europeans by sex and region using SHARE data

Article References: Llorens-Ortega, R., Bertran-Noguer, C., Juvinyà-Canal, D., Garre-Olmo, J., & Bosch-Farré, C. (2026). Intrinsic capacity and changes in quality of life among older Europeans by sex and region using SHARE data. Discover Social Science and Health. https://doi.org/10.1007/s44155-026-00484-6

Image Credits: AI Generated

DOI: 10.1007/s44155-026-00484-6

Keywords: intrinsic capacity, quality of life, aging, older adults, SHARE, sex differences, regional disparities, depressive symptoms, mobility, CASP-12, healthy aging, Europe