Concurrent physical frailty and depression likely boost the risk of dementia in older people, with the interaction of these two factors alone contributing around 17 per cent of the overall risk, suggest the findings of a large international study.

Globally, some 57 million people are living with dementia – a figure that is expected to triple by 2050, the researchers noted.

Previously published research has primarily focused on the individual associations between physical frailty or depression and dementia risk, despite the fact that both have physiological and pathological factors in common, the researchers said.

The researchers wrote: “These results underscore the complex relationship between frailty, depression, and cognitive function.”

To explore the potential interaction between these factors on dementia risk in older adults,  the researchers tracked the diagnosis of any type of dementia in 220,947 participants (average age: 64; 53 per cent women) from three large study groups.

These were the UK Biobank, the English Longitudinal Study of Ageing (ELSA), and the Health and Retirement Study.

Physical frailty was assessed using modified versions of the Fried frailty criteria, in which a person is considered to be frail if they have three or more of the following indicators: unintentional weight loss; self-reported exhaustion; low physical activity; slow walking speed; and weak grip strength.

Depression was evaluated through responses to mental health questionnaires or combined with hospital admission records.

Compared with those in good physical health, frail participants across all three groups were older, more likely to be female, weigh more, have more long term conditions and lower educational attainment.

During an average tracking period of nearly 13 years, 9088 people (7605 in the UK Biobank, 1207 in the Health Retirement Study and 276 in the ELSA) were diagnosed with dementia of any type.

Analysis of the data revealed that compared with those in good physical health, those who were frail were more than 2.5 times as likely to be diagnosed with dementia, while depression was associated with a 59 per cent heightened risk.

And participants who were both physically frail and depressed were more than 3 times as likely to be diagnosed with dementia as those in good physical and mental health.

What’s more, a significant additional interaction between physical frailty and depression was observed, with around 17 per cent of the overall dementia risk attributable to these two factors combined.

The researchers wrote: “Lower levels of frailty may allow the health system to partially offset the cognitive burden of depression and, similarly, lower levels of depression may enable the system to mitigate the burden of frailty.”

They added: “Given that physical frailty and depression are modifiable, concurrent interventions targeting these conditions could significantly reduce dementia risk.”

A decline in personal confidence or concentration during midlife could signal an elevated risk of developing dementia later in life, new research suggests.

Researchers identified six specific symptoms in middle age that may serve as early markers of underlying neurodegenerative processes, meaning gradual damage to brain cells.

The findings stem from an analysis of data from 5,811 participants in the UK Whitehall II study, who provided detailed information on their health, including mental wellbeing.

During a follow-up period of an average of 23 years, 586 people developed dementia.

Lead author Dr Philipp Frank, from the UCL division of psychiatry, said: “Our findings show that dementia risk is linked to a handful of depressive symptoms rather than depression as a whole.

“This symptom-level approach gives us a much clearer picture of who may be more vulnerable decades before dementia develops.”

Everyday symptoms that many people experience in midlife appear to carry important information about long-term brain health.”

“Paying attention to these patterns could open new opportunities for early prevention.”

Academics at University College London identified six depressive symptoms that emerged as robust midlife indicators of increased dementia risk: losing confidence in oneself; not being able to face up to problems; not feeling warmth and affection for others; feeling nervous and strung up all the time; not being satisfied with the way tasks are carried out; and difficulties concentrating.

Those who reported that they had lost confidence in themselves in midlife appeared to carry a 51 per cent increased risk of dementia in later life.

People who said they were not able to face up to their problems had a 49 per cent increased risk.

Reporting not feeling warmth and affection for others carried a 44 per cent raised risk, while feeling nervous and strung up held a 34 per cent rise in risk of dementia later in life.

Those who were not satisfied with the way tasks are carried out had a 33 per cent increased risk of dementia more than 20 years later, while those who reported difficulties concentrating had a 29 per cent elevated risk.

Professor Mika Kivimaki, from the UCL faculty of brain sciences, who leads the Whitehall II study and co-authored the paper, said: “Depression doesn’t have a single shape — symptoms vary widely and often overlap with anxiety.”

“We found that these nuanced patterns can reveal who is at higher risk of developing neurological disorders.”

Dr Richard Oakley, associate director of research and innovation at Alzheimer’s Society, added: “The connection between dementia and depression is complicated.

“It’s encouraging to see this new observational study begin to unpick how dementia and depression are interlinked.

“However, more research is needed to confirm whether these six symptoms also apply to women and ethnic minorities.

“It’s important to note that not everyone who has depression will go on to develop dementia, and people with dementia won’t necessarily develop depression.”

South Korea’s ADEL has signed a US$1.04bn Alzheimer’s partnership with Sanofi to develop and sell an experimental antibody now in early US trials.

Under the agreement, ADEL receives an upfront US$80m, plus milestones tied to development and commercial progress, and royalties on future sales.

Sanofi also signed a separate deal with private biotech Dren Bio worth up to US$1.7bn on the same day to develop autoimmune therapies.

The drug candidate, ADEL-Y01, is an antibody that targets tau acetylation. Tau is a brain protein that helps stabilise nerve cells; acetylation is a chemical tag linked to harmful build-up seen in Alzheimer’s.

“ADEL’s innovative approach to targeting tau acetylation offers a promising and differentiated mechanism for addressing the underlying causes of Alzheimer’s disease.” said Erik Wallstroem, global head, multiple sclerosis, neurology and gene therapy development at Sanofi.