Journal of Neurology Neurosurgery and Psychiatry - BMJ Group

Significant variations in survival times of early onset dementia by clinical subtype

Hannah Ahmed — Wed, 05 Nov 2025 10:30:39 +0000

But sex, age, family history, co-existing conditions not specific risk factors
Impact on risk of death from any cause even greater than it is in others of same age

The survival rates of people with early onset dementia—diagnosed before the age of 65—vary considerably by clinical type, but sex, age, family history and co-existing conditions aren’t specific risk factors, finds research published online in the Journal of Neurology Neurosurgery & Psychiatry.

Although the survival of those afflicted by dementia in older age is shorter, the overall impact on the risk of death from any cause is even greater in those with early onset disease than it is in others of comparable age, say the researchers.

Around 5% of dementia cases globally are categorised as early onset. But while dementia is widely recognised as a life-limiting condition among elderly people, few studies have assessed survival times and the factors associated with prognosis in those with early onset disease, explain the researchers.

To explore this further and help inform the treatment and care provision of those diagnosed with early onset dementia, the researchers reviewed and reassessed all 12,490 visits made to dementia outpatient clinics in two university hospital districts in Finland between 2010 and 2021.

Some 794 confirmed cases of early onset dementia were identified, to include Alzheimer’s disease, frontotemporal dementia, alpha-synucleinopathies (in particular, Lewy body dementia), and ‘other’ and ‘mixed’ dementia, which included vascular cognitive impairment.

The survival times of each of these cases was compared with those of 10 people without neurodegenerative disease, but matched for age, sex, and geographical region, from general population data registers (7930 people in total).

During the study period, 215 people with early onset dementia died. Their average survival time was nearly 9 years, but varied according to disease subtype.

The shortest survival time of nearly 7 years was seen among those with frontotemporal dementia or Lewy body dementia (7 years), although those with both frontotemporal dementia and motor neurone disease (ALS) lived for just over 2 years, on average.

Those with Alzheimer’s disease lived for nearly 10 years, on average, while those with vascular cognitive impairment lived the longest—over 10 years, on average.

Compared with those without neurodegenerative disease, the death rate from any cause among those with early onset dementia was more than 6.5 times higher. But when categorised by disease subtype, it was nearly 14 times as high in those with frontotemporal dementia, and more than 4 times as high among those with vascular cognitive impairment, for example.

Male sex, older age, several co-existing conditions, and lower educational attainment were all universally associated with an increased risk of death, but they weren’t specific to early onset dementia. It was the diagnosis of early onset dementia itself that was most strongly and independently associated with survival time, say the researchers.

Only diabetes, which is a known risk factor for dementia, was associated with shorter survival time among those with early onset dementia.

“Overall, although the survival time in years appears shorter in older patients, the impact of dementia diagnosis on all-cause mortality is more significant in the [early onset dementia] age group than in the late onset patients when compared with the general population,” comment the researchers.

This is an observational study, and no definitive conclusions can be drawn about cause and effect. The researchers also acknowledge various limitations to their findings, including that most of the study participants had no genetic or neuropathological confirmation of their dementia. And the numbers in each clinical subgroup were small.

“Our study provides up-to-date [early onset dementia] survival rates in a validated population-based [early onset dementia] cohort, and highlights the substantial effect caused by [its] diagnosis on patients’ mortality,” conclude the researchers.

“Accurate up-to-date data on the survival and mortality rates of [early onset dementia] are crucial in designing healthcare structures, comprehensive patient care, and clinical trials,” they add.

04/11/2025

Notes for editors
Research: Survival and mortality rates in early onset dementia Doi: 10.1136/jnnp-2025-336805
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: Jane and Aatos Erkko Foundation; Wihuri Research Institute; Uulo Arhio Memorial Foundation; Päivikki and Sakari Sohlberg Foundation; Research Council of Finland; Roche; Sigrid Jusélius Foundation; Finnish Brain Foundation; Finnish Cultural Foundation; Finnish Medical Foundation; Finnish Parkinson Foundation

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

About the journal
The Journal of Neurology Neurosurgery & Psychiatry is one of 70 journals published by BMJ Group.
https://jnnp.bmj.com

Externally peer reviewed? Yes
Evidence type: Observational
Subjects: People

The post Significant variations in survival times of early onset dementia by clinical subtype first appeared on BMJ Group.

Driving global consensus on Alzheimer’s disease imaging

shelley — Wed, 30 Jul 2025 13:34:01 +0000

A collaboration of expertise

Neurologists ensured imaging advances align with clinical needs and disease understanding

Radiologists identified the most accurate imaging methods for diagnosis and monitoring

MRI physicists optimised protocols for sensitive and reliable detection of brain changes

Public health experts addressed system feasibility and ethical access to therapies

Clinical trial investigators shared practical insights from Phase 3 DMT studies for safe monitoring

Policymakers and guideline developers translated consensus into standardised, actionable protocols

Low LDL cholesterol levels linked to reduced risk of dementia

Hannah Ahmed — Wed, 02 Apr 2025 12:57:42 +0000

Use of statins lowered risk of dementia even further in people with low LDL levels

People with low levels of low-density lipoprotein cholesterol (LDL-C) in their blood have a lower risk of dementia, including lower risk of Alzheimer’s disease related dementia, shows a study published online today in the Journal of Neurology Neurosurgery & Psychiatry.

Use of statins conveyed an additional protective effect for people with low LDL-C, specifically those with blood levels less than 1.8 mmol/L (<70 mg/dL), reducing their risk of dementia even further.

However, reducing LDL-C to very low levels below 0.8 mmol/L (<30mg/dL) did not reduce dementia risk further.

The benefits of low LDL-C levels to protect against cardiovascular events is well recognised, but the relationship between LDL-C levels and dementia has been less clear, particularly the cut-off for LDL-C below which there is no further benefit for reducing risk of cognitive decline.

To address this, the authors accessed data collected by 11 university hospitals on adult outpatients with no previous diagnosis of dementia followed for at least 180 days after LDL-C testing. They identified 192,213 people with LDL-C levels less than 1.8 mmol/L (<70mg/dL) and 379,006 patients with LDL-C levels more than 3.4 mmol/L (>130mg/dL), and matched individuals in each group into 108,980 matched pairs.

Analysis of subsequent diagnoses of dementia showed that LDL-C levels below 1.8 mmol/L (<70mg/dL) were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of Alzheimer’s disease related dementia, compared with LDL-C levels above 3.4 mmol/L (>130mg/dL).

The protective effect against cognitive decline lessened at lower LDL-C levels and eventually disappeared entirely. At LDL-C levels below 1.4 mmol/L (<55mg/dL), there was an 18% risk reduction for both all cause dementia and Alzheimer’s disease related dementia compared with LDL-C levels above 3.4 mmol/L (>130mg/dL), and when LDL-C levels fell below 0.8 mmol/L (<30mg/dL) the risk reductions disappeared.

Statin use conferred additional protection against dementia in the presence of low LDL-C levels. Among people with LDL-C levels below 1.8 mmol/L (<70mg/dL), statin use was associated with a 13% reduction in all cause dementia risk and a 12% decrease in risk of Alzheimer’s disease related dementia compared with non-users.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. The authors also acknowledge that the study has some limitations including the potential for unmeasured confounding factors because of its retrospective design, possible underreporting of dementia cases due to variations in diagnostic accuracy between hospitals, and the focus on baseline LDL-C levels when lipid profiles could change over time.

Nevertheless, the authors conclude: “Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including Alzheimer’s disease related dementia, with statin therapy providing additional protective effects.”

They add: “These findings underscore the crucial role of managing LDL-C in lowering dementia risk.”

02/04/2025

Notes for editors
Research: Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models doi:10.1136/jnnp-2024-334708
Journal: Journal of Neurology Neurosurgery & Psychiatry

Funding: National Research Foundation of Korea and the Korean Neurological Association

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Observational
Subjects: People

The post Low LDL cholesterol levels linked to reduced risk of dementia first appeared on BMJ Group.

High dietary fish intake may slow disability progression in MS

Hannah Ahmed — Wed, 26 Feb 2025 10:11:32 +0000

Anti-inflammatory, neuroprotective properties of nutrients found in fish may be key
Findings underscore potential importance of diet in managing MS, say researchers

A high dietary intake of lean and oily fish may slow the progression of disability in people with multiple sclerosis (MS), suggests a comparative population based study, published online in the Journal of Neurology Neurosurgery & Psychiatry.

The anti-inflammatory and neuroprotective properties of the nutrients found in fish may be key, say the researchers, who add that their findings underscore the potential importance of diet in managing the disease.

Emerging evidence indicates that diet may have a role in the development of inflammatory diseases, including MS, explain the researchers.

While previously published research has linked fish consumption with lower levels of disability among those with MS, few studies have looked at whether it might slow or lessen the progression of disability, they point out.

To explore this further, they drew on 2719 newly diagnosed participants (average age 38) in The Epidemiologic Investigation of Multiple Sclerosis (EIMS) study, a Swedish nationwide population based case-control study, all of whom were recruited between April 2005 and June 2015.

On entry to EIMS, all participants provided information on environmental exposures and lifestyle habits, including their consumption of lean and oily fish, which was categorised as: never or seldom; 1 to 3 times a month; and weekly, and scored from 2 to 6, depending on whether they ate lean or oily fish, or both.

Their disease progression, measured using the Expanded Disability Status Scale (EDSS), was tracked for up to 15 years through the Swedish MS Registry.

Confirmed disability worsening was defined as an increase in the EDSS score of at least 1 point from baseline, sustained between two further check-ups, at least 6 months apart.

The highest fish consumption at diagnosis was associated with a 44% lower risk of confirmed disability worsening as well as a 45% lower risk of progressing to EDSS 3 and and a 43% lower risk of progressing to EDSS 4 compared with those who ate none or very little.

And the more lean and oily fish that was consumed, the lower was the risk of confirmed disability worsening and progression to EDSS 3 and 4, trends analysis indicated.

In 2021, 1719 participants completed an online follow-up questionnaire which assessed changes in fish intake over time. Some 412 (24%) had altered their fish consumption: 288 had increased it; 124 had decreased it.

Those who increased their score from 2–3 to a score of 5–6 within 5 years after diagnosis (133) had a 20% lower risk of confirmed disability worsening, compared with those who continued to eat little or no fish (400).

Only 16 participants increased their fish consumption from a baseline score of 2 to a score of 5–6, but they had a 59% lower risk of confirmed disability worsening, compared with those who remained at the lowest level of consumption (101).

The findings held true even when the potentially influential factors of physical activity, weight (BMI), smoking, alcohol intake, and sun exposure were accounted for. They also remained similar when further adjustment was made for vitamin D level.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And further research to validate the findings and investigate the underlying biological mechanisms is required, say the researchers.

But they suggest: “While omega-3 fatty acids, predominantly found in oily fish, may contribute to reduced disability progression, the beneficial effects observed from lean fish consumption suggest that other factors may also play a significant role. One such factor is taurine, an amino acid found in significant amounts in fish and seafood.”

They explain: “Taurine is the most abundant free amino acid in the brain and, although there are endogenous mechanisms for its production, an exogenous supply is necessary to meet physiological needs.”

They add: “Taurine has diverse cellular functions, including cytoprotective actions through antioxidative and anti-inflammatory effects, making it a potential therapeutic agent for neurological disorders.”

And they conclude: “The results underscore the potential role of diet, particularly fish consumption, as a modifiable factor that could complement existing therapeutic strategies for MS.”

Notes for editors
Research: Impact of fish consumption on disability progression in multiple sclerosis Doi: 10.1136/jnnp-2024-353200
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Swedish Brain Foundation; Swedish Medical Research Council; Margaretha af Ugglas Foundation; Swedish Foundation for MS Research; NEURO Sweden

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Observational case-control study
Subjects: People

The post High dietary fish intake may slow disability progression in MS first appeared on BMJ Group.

Cutting early life exposure to parental smoking may lower MS risk in genetically prone

Hannah Ahmed — Wed, 11 Dec 2024 11:09:21 +0000

Interplay of genes + environment alter key aspects of brain structure at young age, boosting susceptibility

Cutting early life exposure to parental smoking may lower the risk of developing MS (multiple sclerosis) in those who are genetically predisposed to the disease, finds research published online in the Journal of Neurology Neurosurgery & Psychiatry.

The interplay of genes and environmental factors, including smoking, alter key aspects of brain structure in early childhood, likely facilitating development of the disease and suggesting that there may be a window of opportunity to stave this off, conclude the researchers.

MS is an autoimmune disease that is typically diagnosed between the ages of 20 and 40. But it’s not clear if it stems from early inflammatory brain damage or a latent neurodegenerative process overlaid with inflammation, explain the researchers.

Exactly when the disease process begins isn’t known either. But brain volume loss and poorer cognitive performance before clinical signs and symptoms appear suggests that these precede diagnosis.

Studies on migration show that early life environmental factors have a key role, but exactly how these interact isn’t yet known, they add.

To shed more light on how and when the interplay of environmental and genetic risk factors might affect brain volume, and so facilitate future MS development, the researchers used data from the population based Dutch Generation R study.

Participants in this study had good quality data on genotype and/or the known environmental risk factors of Epstein Barr virus infection, vitamin D levels, weight (BMI), parental tobacco exposure, and outdoor activity at the age of 5, plus high quality brain scan images at the ages of 9 and 13.

In all, the researchers drew on imaging data showing brain volume for 5350 participants and brain microstructure for 5649 participants, none of whom had been diagnosed with MS.

Polygenic risk scores, derived from DNA samples, were used to assess genetic risk of developing MS, with the genetic variant rs10191329, used as a marker of future MS severity.

In all, 642 children tested positive for Epstein Barr virus infection and 405 had been exposed to household parental smoking.

The final analysis was based on genetic data from 2817 participants and brain volume and microstructure imaging data from 2970 participants.

This showed an interplay between genetic and environmental risk factors for MS that was associated with certain aspects of brain structure during childhood and the early teens.

Specifically, higher genetic risk for MS was associated with a strong immune response to Epstein-Barr virus infection, and it was also associated with increased susceptibility to the negative effects of household parental smoking on brain development.

Higher MS genetic risk and household parental smoking interacted and were associated with lower total brain volume and grey matter volume, including thalamic volume.

No associations were observed for carriers of the rs10191229 genetic valiant.

This is an observational study, and as such, no firm conclusions about cause and effect can be drawn.

By way of explanations for the findings, the researchers point out that higher Epstein-Barr virus antibodies may be caused by defective immune system control of this virus due to genetic risk for MS, possibly facilitating development of the disease later in life.

And the prevailing theory is that tobacco smoke produces chronic inflammation of the respiratory tract, thereby increasing the inflammatory activity of the immune system, they add.

“Our results importantly add another potential mechanism of tobacco smoke exposure in individuals with higher polygenic MS risk. The increased brain vulnerability to the effects of parental smoking may increase exposure of [central nervous system] antigens to the developing immune system, increasing the risk of a brain specific autoimmune disease,” they suggest.

“How this increased vulnerability influences other MS risk factors may open a window for prevention of MS by limiting childhood exposure to household smoking or other toxic exposures associated with MS (ie, household chemicals), and should be a focus for further studies,” they conclude.

11/12/2024

Notes for editors
Research: Environmental multiple sclerosis (MS) risk factors, genetic MS risk, and brain development in a general paediatric population Doi: 10.1136/jnnp-2024-335053
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: Dutch MS Research Foundation

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Observational
Subjects: People

The post Cutting early life exposure to parental smoking may lower MS risk in genetically prone first appeared on BMJ Group.

Men at high risk of cardiovascular disease face brain health decline 10 years earlier than women

Hannah Ahmed — Wed, 27 Nov 2024 12:54:46 +0000

Most vulnerable regions those involved in aural, visual + emotional processing, and memory
Findings observed both in those who did and didn’t carry high risk APOE ε4 gene

Men with cardiovascular disease risk factors, including obesity, face brain health decline a decade earlier—from their mid 50s to mid 70s—than similarly affected women who are most susceptible from their mid 60s to mid 70s, suggest the findings of a long term study, published online in the Journal of Neurology Neurosurgery & Psychiatry.

The most vulnerable regions of the brain are those involved in processing auditory information, aspects of visual perception, emotional processing and memory, with the damaging effects just as evident in those who didn’t carry the high risk APOE ε4 gene as those who did, the findings show.

It’s clear that cardiovascular disease risk factors, such as type 2 diabetes, obesity, high blood pressure, and smoking are associated with a heightened risk of developing dementia.

But when might be the best time to intervene with appropriate treatment to stave off the associated neurodegeneration, and whether this timing might differ between the sexes, isn’t clear, say the researchers.

To explore this further, they drew on 34,425 participants of the UK Biobank all of whom had had both abdominal and brain scans. Their average age was 63, but ranged from 45 to 82.

Cardiovascular disease risk was assessed using the Framingham Risk Score, which is based on: age; blood fats; systolic blood pressure—the maximum arterial pressure exerted when the heart contracts and pumps blood, and represented by the first higher number in a reading—blood pressure medication; smoking; and diabetes.

Additionally, changes in brain structure and volume were recorded using a neuroimaging technique called Voxel-based morphometry (VBM) to identify the influence of cardiovascular risk, abdominal fat, and the fat that surrounds body organs (visceral adipose tissue) on brain neurodegeneration.

Analysis of the data showed that higher levels of abdominal fat and visceral adipose tissue were associated with lower brain grey matter volume in both men and women.

The strongest influence of cardiovascular risk and obesity on brain neurodegeneration occurred a decade earlier in men than in women and was sustained over two decades, the data revealed. The effects were also stronger in men than they were in women.

Men were most susceptible to the damaging effects between the ages of 55 and 74, while women were most susceptible between the ages of 65 and 74.

High cardiovascular risk and obesity predisposed to gradual loss of brain volume over several decades, occurring in a bell-shaped curve over time, with susceptibility lower at younger (under 55) and older ages (75+), although there were relatively few participants of either sex in these age groups, note the researchers.

Importantly, the associations remained, irrespective of whether or not those affected were carriers of the high risk APOE ε4 gene.

The most vulnerable regions of the brain were the temporal lobes, located in the cerebral cortex, the brain’s outer surface. These regions are involved in aural, visual, and emotional information processing, and memory—regions affected early on in the development of dementia.

“The detrimental impact of cardiovascular risk was widespread throughout cortical regions, highlighting how cardiovascular risk can impair a range of cognitive functions,” note the researchers.

“Therefore, modifiable cardiovascular risk factors, including obesity, deserve special attention in the treatment/prevention of neurodegenerative diseases, including Alzheimer’s disease,” they add.

“This highlights the importance of aggressively targeting cardiovascular risk factors before the age of 55 years to prevent neurodegeneration and Alzheimer’s disease, in addition to the benefit of preventing other cardiovascular events, such as myocardial infarction [heart attack] and stroke,” they emphasise.

“One such possibility may be in the repurposing of agents used for obesity and type 2 diabetes mellitus for the treatment of Alzheimer’s disease,” they suggest, adding that other drugs used for the treatment of cardiovascular disease have also shown promise.

This is an observational study, so no firm conclusions can be drawn about cause and effect. And the researchers acknowledge various limitations to their findings, including that the UK Biobank didn’t record specific biomarkers for Alzheimer’s disease.

Atrophy of frontal, parietal, and temporal brain regions is also typical of normal ageing, making it difficult to precisely differentiate between the impact of cardiovascular risk on general ageing processes and the risk of specific neurodegenerative conditions, they add.

But there are plausible biological explanations for the observed neuronal damage, they explain. These include inflammation, central leptin and insulin resistance, as well as the breakdown of the blood-brain barrier.

And they conclude: “Targeting cardiovascular risk and obesity a decade earlier in males than females may be imperative for potential candidates to achieve a therapeutic benefit in preventing neurodegeneration and cognitive decline.”

27/11/2024

Notes for editors
Research: Cardiovascular risk and obesity impact loss of grey matter volume earlier in males than females Doi: 10.1136/jnnp-2024-333675
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: None declared

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Observational
Subjects: People

The post Men at high risk of cardiovascular disease face brain health decline 10 years earlier than women first appeared on BMJ Group.

No major concerns about risks to offspring for would-be dads taking epilepsy meds

Hannah Ahmed — Wed, 18 Sep 2024 11:10:23 +0000

Evidence on antiseizure drugs is inconsistent; but most studies show no heightened risk
Findings cast doubt cast on stance taken by UK drugs regulator, say authors

Would-be dads taking drugs to stop their epilepsy seizures—and valproate in particular—should be largely reassured that the available evidence on the developmental risks to their offspring doesn’t justify any major concerns, concludes a systematic review of relevant studies published online in the Journal of Neurology Neurosurgery & Psychiatry.

The available evidence is scarce and inconsistent, but most studies indicate no heightened risk, the findings show, casting doubt on the stance taken by the UK drugs regulator, the MHRA, in particular, say the authors.

The use of valproate during pregnancy is already restricted because of strong evidence showing that it’s harmful to the developing fetus. And experimental animal studies have linked antiseizure drugs to male infertility and congenital and behavioural abnormalities in their offspring, sparking concerns that these findings might also apply to men.

To explore this further, the authors trawled research databases for studies published in English that reported on neurodevelopmental disorders, major congenital abnormalities, low birthweight or smaller than expected size at birth, among the babies of fathers taking antiseizure drugs when the child was conceived.

Out of an initial haul of 923 articles, 26 underwent full-text review for eligibility, yielding 10 for inclusion in the final review.

This showed that although the data were limited, there was no clear evidence of a detrimental impact of these drugs on the studied outcomes in men taking them. A few isolated harmful side effects weren’t replicated in other investigations.

Several methodological limitations prevented pooled data analysis of the individual study results, including the failure to report outcomes separately for each drug, wide variations in measurement and outcome reporting, and the small numbers of men taking just one drug.

The European drugs regulator, the EMA, commissioned a retrospective observational study drawing on Scandinavian registry data. Yet to be peer reviewed, this suggests that there may be an estimated 5% increased risk of neurodevelopmental disorders in children born to men taking valproate in the 3 months before conception compared with around 3% for two other antiseizure drugs—lamotrigine and levetiracetam.

The EMA, however, concluded that it wasn’t possible to establish whether the increased risks were due to valproate, because of various important methodological limitations.

And in January 2024 it recommended that valproate could be prescribed for men with epilepsy, bipolar disorder, or migraine, provided treatment is supervised and patients are advised of the possible risks and use contraception. And it recommended regular reviews to assess the suitability of the treatment when planning to father a child.

But the UK drugs regulator, the MHRA, took a more restrictive stance, prohibiting starting anyone under the age of 55 on valproate unless there was no other effective and well tolerated alternative or where there was absolutely no possibility of new parenthood.

And this month, the MHRA updated its safety guidance for men, advising that they should be aware of the potentially increased risk and should use contraception while taking the drug and for 3 months after stopping treatment.

“The wisdom of the UK regulatory changes has been questioned,” point out the review authors, adding that not prescribing valproate “is likely to lead to an increased risk of morbidity and mortality, including an increased risk of sudden unexpected death in epilepsy (SUDEP).”

They acknowledge that the quality of the studies included in their review was variable and that the potential reproductive implications of taking antiseizure drugs in men have not been sufficiently studied. This clearly needs to be addressed, they emphasise.

But they suggest: “In view of the findings of this systematic review, particularly the reassuring results from the recent large population-based study from Denmark, the MHRA restrictions regarding the use of valproate in men should be reappraised and potentially revised.”

In a linked editorial, Professor Torbjörn Tomson, of the Karolinska Institutet, agrees. “These peer-reviewed data, highlighted in the current systematic review, contradict the observations reported from the EMA-initiated study, with its limitations, and call for a reconsideration of, in particular, the MHRA restrictions,” he says.

“It is questionable to refer to the restriction as a precautionary measure when they place male patients with generalised epilepsies at risk of inadequate seizure control with potentially fatal consequences,” he continues.

“Potential risks with paternal exposure will remain a hot topic, but it is difficult to see how more conclusive evidence regarding valproate could be generated within the next few years.” he concludes.

18/09/2024

Notes for editors
Systematic review: Paternal exposure to antiseizure medications and offspring outcomes: a systematic review Doi: 10.1136/jnnp-2024-334077
Editorial: Paternal exposure to antiseizure medications and offspring outcomes Doi 10.1136/jnnp-2024-334474

Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: None declared

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes (research); No (editorial)
Evidence type: Systematic Review (research); Opinion (editorial)
Subjects: Men

The post No major concerns about risks to offspring for would-be dads taking epilepsy meds first appeared on BMJ Group.

Lack of purpose and personal growth may precede mild cognitive impairment

Hannah Ahmed — Wed, 14 Aug 2024 17:00:56 +0000

These aspects of psychological wellbeing noticeably decline before diagnosis

Feeling that your life lacks purpose and that there are few opportunities for personal growth in older age may precede the development of mild cognitive impairment (MCI), a frequent precursor of dementia, suggests research published online in the Journal of Neurology Neurosurgery & Psychiatry.

These aspects of psychological wellbeing noticeably decline 2 to 6 years before MCI is diagnosed, even in the absence of evident signs, and irrespective of whether those affected go on to develop dementia, the findings indicate.

Mounting evidence links psychological wellbeing to brain ageing, including the development of dementia. But much of the published research focuses on a sense of purpose, excluding the other aspects of wellbeing, explain the researchers.

These include self-acceptance, autonomy, feeling capable of managing one’s immediate environment, having meaningful connections with others, and personal growth.

To strengthen the evidence base, the researchers explored changes over time in psychological wellbeing before and after diagnoses of MCI and dementia among 910 cognitively intact older adults (average age 79) participating in the Rush Memory and Aging Project.

This Project is an ongoing long term study that began in 1997. It includes older adults from senior and subsidised housing, continuous care retirement communities, social service agencies, church groups, and individual homes in northeastern Illinois, USA.

Study participants have annual check-ups that include neurological examinations, cognitive tests, medical history, and assessment of psychological wellbeing, which from 2008 onwards included all 6 components.

During an average monitoring period of 14 years, 265 (29%) developed MCI, 89 (34%) of whom went on to develop dementia. The final analysis is based on 229 participants with complete before and after data, including 73 who developed dementia.

Compared with participants who remained cognitively intact, those who developed MCI were more likely to be older, weigh less, and have lower levels of depressive symptoms and psychological wellbeing.

Similarly, compared with those who didn’t develop dementia, those who did were more likely to be older, female, to carry the gene linked to dementia (APOE ε4), and to have a lower level of psychological wellbeing.

After accounting for potentially influential factors, such as age, vascular disease and its risk factors, lifestyle, social activities and feelings of loneliness, those who developed MCI experienced a faster decline in psychological wellbeing, leading to a lower level of it 2 years before diagnosis, than those who remained cognitively intact.

In particular, these people had lower levels of purpose in life and personal growth, beginning 3 and 6 years, respectively, before their diagnosis.

The speed of psychological wellbeing decline was similar before and after their diagnosis for each component except for meaningful connections with others, which declined faster afterwards.

Wellbeing trajectories were similar for all participants with MCI regardless of whether they subsequently developed dementia, prompting the researchers to suggest that their findings “indicate that reduced psychological wellbeing even without apparent cognitive impairment may be a predictor of subsequent dementing disorders.”

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. The study participants were well educated, which may introduce selection bias because of the ‘healthy volunteer’ effect, and most of them were White and female, which may limit the generalisability of the findings, acknowledge the researchers.

And the mechanisms underlying the association between wellbeing and cognitive function aren’t well understood, they add.

The two might be bi-directional: in other words, poorer cognition might influence psychological wellbeing as well as the other way round; greater wellbeing and better cognitive function may also share certain protective factors, they suggest.

And the discrepancies across the various wellbeing components may lie in differences in the level of cognitive processing required, they say.

“Our findings indicate that personal growth and purpose in life may be more cognitively demanding than other components of wellbeing, and therefore may serve as more sensitive indicators of cognitive ageing,” they write.

“Moreover, we found that positive relations with others declined rapidly after MCI diagnosis. People with impaired cognitive function may be less likely to engage in social and leisure activities than they were previously, which can cause further deterioration in their relationships with friends or others,” they add.

Psychological support should be planned for people diagnosed with dementing disorders, they advocate.

14/08/2024

Notes for editors
Research: Psychological well-being trajectories preceding incident mild cognitive impairment and dementia Doi: 10.1136/jnnp-2024-333837
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: National Institutes of Health; Swedish Research Council; Lindhés Advokatbyrå AB

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Observational
Subjects: People

The post Lack of purpose and personal growth may precede mild cognitive impairment first appeared on BMJ Group.

Few UK people likely to be suitable for new Alzheimer’s drugs when they come on stream

Hannah Ahmed — Fri, 12 Jul 2024 17:30:41 +0000

But many people with memory loss nevertheless likely to be referred for these treatments

Few people in the UK with early stage Alzheimer’s disease are likely to be suitable for the latest drugs which aim to halt progress of the condition, yet many are nevertheless likely to be referred for these treatments, finds research published online in the Journal of Neurology Neurosurgery & Psychiatry.

The disease-modifying drugs, lecanemab and donanemab, slow cognitive decline in people with early stage Alzheimer’s disease. And they have been granted ‘breakthrough therapy’ status in the UK because of their ability to remove beta amyloid protein in the brain, build-up of which is thought to have a key role in the development of the disease.

Already licensed for the treatment of Alzheimer’s disease in the US in 2023, regulatory approval of these drugs for use in the UK is expected shortly. But to maximise their effectiveness, a raft of clinical staff and diagnostic and monitoring tests and scans will be required, point out the researchers.

To gauge the potential level of healthcare demand, the researchers retrospectively evaluated patients attending 5 community memory services across North and East London and a national specialist cognitive disorders service between January and June in 2022.

They wanted to find out the proportion of patients who would likely be referred for triaging from the memory services for these new drugs as well as those from the specialist service who would potentially be suitable for treatment with them.

In all, the anonymised case files of 1017 patients were included, 517 of whom were seen in community memory services and 500 in specialist clinics.

Just over 40% of the memory service patients were men; their average age was 79, with just 14% (72) under the age of 70. After exclusions due to incomplete data and factors, such as symptom severity, frailty, and other coexisting conditions, nearly 1 in 3 (163; 31.5%) were potentially eligible for treatment with the new drugs.

Of these,161 had undergone neuroimaging; but fluid biomarker tests were carried out in only 2 patients. This is equivalent to less than 1% of the memory clinic patients included in the study, “making this an urgent area of need for service development to enable identification of suitable patients,” emphasise the researchers.

Based on these figures, they suggest: “With an average memory clinic caseload of 815 and 80 nationally accredited memory clinics in England and Northern Ireland, potentially over 20,000 people per year will need access to such confirmatory investigations.”

More of the specialist clinic patients were men (53%) and they tended to be younger. Their average age was 66, but well over half (58%; 290) were under the age of 70. Alzheimer’s disease was the most common diagnosis (177;35.5%), followed by frontotemporal dementia (72;14.5%).

Most of them (492) had been given diagnostic scans: computed tomography or magnetic resonance imaging. And fluid biomarker tests were performed in nearly two thirds (62%;109/177) of those with Alzheimer’s disease.

But after exclusions due to frailty and contraindications for treatment, etc, only 40% (70) of the Alzheimer’s disease patients were potentially eligible for treatment with the new drugs, equivalent to just 14% of all the cases reviewed at the specialist cognitive clinics.

“Systems need to be set up to deal with this potential large mismatch between referral and ultimate eligibility in order to avoid overwhelming services,” highlight the researchers.

They add: “A significant issue is that due to the lack of biomarker testing in community memory clinics, the clinical suspicion of [Alzheimer’s disease] is likely to be incorrect in at least 30% of cases.”

Accurate diagnosis would reduce the number of patients ultimately eligible for the new therapies. But that would only be possible with confirmatory fluid biomarkers or brain (PET) scans, which aren’t usually available to memory services in the UK, they point out.

“While there are limitations on the accuracy of our estimates, given current barriers to early clinical presentations and referral, our study provides predicted numbers based on real-world community cohorts,” they write.

Demand for diagnostic services among those with early cognitive concerns is only likely to grow once the new drugs have been licensed and formally appraised by the National Institute for Health and Care Excellence, “placing further demands on already overstretched services,” they warn.

“While a sizeable proportion of patients attending memory clinics may be referred for triaging for [disease modifying drugs for Alzheimer’s disease], only a minority are likely to be suitable for these, as demonstrated in patients seen in specialist cognitive services. This will need to be considered when designing pathways for delivery [of these drugs],” they conclude.

In a linked editorial, Dr Benjamin Underwood, of Fulbourn Hospital, Cambridge, highlights the study limitations. “It is retrospective and several ‘unknowns’ remain, including how many people would choose to have treatment if eligible, how many would meet criteria for ‘amyloid positivity,’ and whether the advent of treatment might encourage more people to present,” he writes.

“Nevertheless, if these treatments are approved for use, the work presented here will help plan services. It also provides a reminder that only a minority of people will be appropriate to receive these treatments. It is essential that services retain focus on the majority of people who will need other forms of treatment and care,” he concludes.

12/07/2024

Notes for editors
Research: Eligibility for anti amyloid treatment: preparing for disease-modifying therapies for Alzheimer’s disease Doi: 10.1136/jnnp-2024-333468
Editorial: Predicting how many people might receive treatment with new therapies for Alzheimer’s disease Doi: 10.1136/jnnp-2024-333941
Journal: Journal of Neurology Neurosurgery & Psychiatry

External funding: None declared

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes (research); No (editorial)
Evidence type: Observational; Opinion
Subjects: People

The post Few UK people likely to be suitable for new Alzheimer’s drugs when they come on stream first appeared on BMJ Group.

Few UK people likely to be suitable for new Alzheimer’s drugs when they come on stream

Ruth Staunton — Tue, 18 Jun 2024 13:51:57 +0000

But many people with memory loss nevertheless likely to be referred for these treatments

In all, the anonymised case files of 1017 patients were included, 517 of whom were seen in community memory services and 500 in specialist clinics.

“Systems need to be set up to deal with this potential large mismatch between referral and ultimate eligibility in order to avoid overwhelming services,” highlight the researchers.

11/06/2024

External funding: None declared

Link to Academy of Medical Sciences Press Release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes (research); No (editorial)
Evidence type: Observational; Opinion
Subjects: People

The post Few UK people likely to be suitable for new Alzheimer’s drugs when they come on stream first appeared on BMJ Group.