Health

The common blood test that predicts how fast Alzheimer’s hits

Insulin resistance detected by routine triglyceride-glucose (TyG) index can flag people with early Alzheimer's who are four times more likely to present rapid cognitive decline, according to new research presented at the European Academy of Neurology (EAN) Congress 2025.¹

Neurologists at the University of Brescia reviewed records for 315 non-diabetic patients with cognitive deficits, including 200 with biologically confirmed Alzheimer's disease. All subjects underwent an assessment of insulin resistance using the TyG index and a clinical follow-up of 3 years. When patients were divided according to TyG index, those in the highest third of the Mild Cognitive Impairment AD subgroup deteriorated far more quickly than their lower-TyG peers, losing >2.5 points on the Mini Mental State Examination per year (hazard ratio 4.08, 95% CI 1.06-15.73). No such link appeared in the non-AD cohort.

"Once mild cognitive impairment is diagnosed, families always ask how fast it will progress," said lead investigator Dr. Bianca Gumina. "Our data show that a simple metabolic marker available in every hospital laboratory can help identify more vulnerable subjects who may be suitable candidates for targeted therapy or specific intervention strategies."

While insulin resistance has been linked to the onset of Alzheimer's disease, its role in how quickly the condition progresses has received less attention. This study aimed to fill that gap by focusing on its impact during the prodromal mild cognitive impairment (MCI) stage, when patients follow highly variable trajectories. The researchers used the TyG index, which offers a low-cost, routinely available surrogate for insulin resistance, to explore whether metabolic dysfunction could help predict the pace of cognitive decline after diagnosis.

In AD specifically, insulin resistance is believed to impair neuronal glucose uptake, promote amyloid accumulation, disrupt the blood-brain barrier, and fuel inflammation - pathways that are less relevant or differently regulated in other neurodegenerative diseases.

"We were surprised to see the effect only in the Alzheimer's spectrum and not in other neurodegenerative diseases," Dr. Gumina noted. "It suggests a disease-specific vulnerability to metabolic stress during the prodromal window, when interventions may still change the trajectory."

The researchers at University of Brescia, led by Professor Padovani and Professor Pilotto, found that high TyG was also associated with blood-brain barrier disruption and cardiovascular risk factors, yet it showed no interaction with the APOE ε4 genotype, indicating that metabolic and genetic risks may act through distinct pathways.²

Identifying high-TyG patients could refine enrolment for anti-amyloid or anti-tau trials and prompt earlier lifestyle or pharmacological measures to improve insulin sensitivity. The researchers are currently investigating whether TyG levels also track with neuroimaging biomarkers to aid earlier detection and stratification.

"If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs," concluded Dr. Gumina.

References:

Gumina B., Galli A., Tolassi C. et al. The Triglyceride-Glucose Index as Predictor of Cognitive Decline in Alzheimer's Spectrum Disorders. Presented at the European Academy of Neurology (EAN) Congress 2025; 23 June 2025; Helsinki, Finland.
Padovani A., Galli A., Bazzoli E., et al. (2025). The role of insulin resistance and APOE genotype on blood-brain barrier integrity in Alzheimer's disease. Alzheimer's & Dementia. Advance online publication. https://doi.org/10.1002/alz.14556 ^[1]

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HIV is surging in over-50s—But campaigns still target the young

Prevention and treatment campaigns are not adequately targeting the particular needs of the 50+ years age group.

Indeed, between 2000 and 2016, the number of adults aged 50 years and older living with HIV in sub-Saharan Africa doubled. At present, their HIV prevalence is exceeding that of younger adults.

By 2040, one-quarter of people living with HIV in Africa will be aged 50 years and older; tailored awareness and treatment campaigns are pressing.

Dr Luicer Olubayo, a researcher at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at Wits University and the first author of a study published in The Lancet Healthy Longevity journal, which investigated HIV in older people in Kenya and South Africa, noted that perceptions on who acquires HIV are limited. "We often think of HIV as a disease of younger people. It doesn't help that intervention campaigns are mainly targeted at the youth."

Moreover, older adults are less likely to believe that they can get HIV. This misconception is pervasive and has consequences for reaching global targets to achieve UNAIDS' 95-95-95 targets by 2030 (95% of people living with HIV know their status, 95% of people who know their status are on treatment, and 95% have a suppressed viral load).

"While HIV prevalence among individuals over 50 years of age is similar to or even exceeds that of younger adults, HIV surveys focus on younger individuals, leaving considerable gaps in understanding HIV prevalence, incidence and treatment outcomes in older populations," says Associate Professor F. Xavier Gómez-Olivé, at the MRC/Wits-Agincourt Research Unit.

Stigma remains a barrier to treatment

The uptake of HIV testing among older adults is poor, which delays diagnosis and limits access to care. This is, indeed, one of the signifiers of the pervasiveness of stigma surrounding the disease.

"We know that there is significant social stigma related to HIV infection. This is why understanding HIV-related stigma in older adults remains crucial as a way to inform interventions to support older people's mental health and overall well-being," says Olubayo.

Interventions could focus on repeated testing, the use of pre-exposure prophylaxis (PrEP), and campaigns to increase awareness and reduce infections among the elderly.

"HIV can be managed alongside other chronic conditions, too, since HIV is managed as a long-term illness," says Gómez-Olivé.

Non-communicable diseases, such as hypertension, diabetes, and obesity, have dramatically increased in sub-Saharan Africa, particularly among older people. HIV treatment and intervention can be included in the healthcare ecosystem of long-term illnesses.

Apart from stigma, a complex interplay of factors shapes HIV risk

The study shows that age, education, gender, and where people live all affect their risk of HIV. Even though more people now have access to HIV treatment, older adults -- especially in rural areas -- still face significant challenges in preventing HIV, such as low education levels and gender inequality.

Widowed women had the highest HIV rate (30.8%). This may be due to losing a partner to HIV, stigma, and a greater risk of unsafe behaviours like transactional sex and limited power to negotiate condom use. People without formal education and those with low income also had higher rates of HIV infection.

The benefit of longitudinal data to make decisions

An important added value of this study is the provision of longitudinal insights into the HIV epidemic among older adults in sub-Saharan Africa. "Our study is beneficial in that older populations are under-represented, and not much is known about them over time. What changes are occurring? We have to answer these kinds of questions. With longitudinal data, we can look at the effectiveness of antiretroviral therapy coverage in older people," says Gómez-Olivé.

The study used data collected in urban Kenya and in urban and rural sites across South Africa during two data collection waves: 2013-2016 and 2019-2022.

Throughout a decade of research, the team has been gaining a deeper understanding of this ageing HIV epidemic. Numerous important insights about HIV in older populations have been achieved, and research gaps are being covered.

Data for the study were drawn from the Africa Wits-INDEPTH Partnership for Genomic Research (AWI-Gen) from adults aged 40 years and older. AWI-Gen is a multicentre, longitudinal cohort study conducted at six research centres in four sub-Saharan African countries (South Africa, Kenya, Burkina Faso, and Ghana) to investigate various health determinants.

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