Apathy not depression helps to predict dementia

July 13, 2020

Science Daily/University of Cambridge

Apathy offers an important early warning sign of dementia in individuals with cerebrovascular disease, but depression does not, new research led by the University of Cambridge suggests.

Depression is often thought to be a risk factor for dementia but this may be because some depression scales used by clinicians and researchers partially assess apathy, say scientists from the universities of Cambridge, King's College London, Radboud and Oxford.

The study, published on 11 July in the Journal of Neurology, Neurosurgery & Psychiatry is the first to examine the relationships between apathy, depression, and dementia in individuals with cerebral small vessel disease (SVD). SVD may occur in one out of three elderly individuals, causes about a quarter of all strokes, and is the most common cause of vascular dementia.

The team studied two independent cohorts of SVD patients, one from the UK and the other from the Netherlands.* Across both cohorts, they found that individuals with higher baseline apathy, as well as those with increasing apathy over time, had a greater risk of dementia. In contrast, neither baseline depression nor change in depression had any detectable influence on dementia risk.

These findings were consistent despite variation in the severity of participants' symptoms, suggesting that they could be generalised across a broad spectrum of SVD cases. The relationship between apathy and dementia remained after controlling for other well-established risk factors for dementia including age, education, and cognition.

Lead author, Jonathan Tay, from Cambridge's Department of Clinical Neurosciences said: "There has been a lot of conflicting research on the association between late-life depression and dementia. Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy."

Apathy, defined as a reduction in 'goal-directed behaviour', is a common neuropsychiatric symptom in SVD, and is distinct from depression, which is another symptom in SVD. Although there is some symptomatic overlap between the two, previous MRI research linked apathy, but not depression, with white matter network damage in SVD.

Jonathan Tay said: "Continued monitoring of apathy may be used to assess changes in dementia risk and inform diagnosis. Individuals identified as having high apathy, or increasing apathy over time, could be sent for more detailed clinical examinations, or be recommended for treatment."

Over 450 participants -- all with MRI-confirmed SVD -- recruited from three hospitals in South London and Radboud University's Neurology Department in the Netherlands, were assessed for apathy, depression and dementia over several years.

In the UK cohort, nearly 20% of participants developed dementia, while 11% in the Netherlands cohort did, likely due to the more severe burden of SVD in the UK cohort. In both datasets, patients who later developed dementia showed higher apathy, but similar levels of depression at baseline, compared to patients who did not.

The study provides the basis for further research, including the mechanisms that link apathy, vascular cognitive impairment, and dementia. Recent MRI work suggests that similar white matter networks underlie motivation and cognitive function in SVD. Cerebrovascular disease, which can be caused by hypertension and diabetes, can lead to network damage, resulting in an early form of dementia, presenting with apathy and cognitive deficits. Over time, SVD-related pathology increases, which is paralleled by increasing cognitive and motivational impairment, eventually becoming severe enough to meet criteria for a dementia state.

Jonathan Tay says: "This implies that apathy is not a risk factor for dementia per se, but rather an early symptom of white matter network damage. Understanding these relationships better could have major implications for the diagnosis and treatment of patients in the future."

https://www.sciencedaily.com/releases/2020/07/200713120022.htm

New findings reveal the interplay between epilepsy and aging

December 7, 2015

Science Daily/American Epilepsy Society

The largest and fastest-growing segment of people with epilepsy are those age 60 and older. People with epilepsy face a number of related health challenges, including cognitive, physical and psychological disorders. But new research suggests other, less expected consequences on the aging process. Four studies presented at the American Epilepsy Society's (AES) 69th Annual Meeting explore the effects of epilepsy on the brain, providing insights that shed light on the long-term implications of life with epilepsy.

People with epilepsy that is unresponsive to medication have brains that appear older than would be expected for their age, according to a study by researchers from New York University Langone Medical Center and Imperial College (abstract 1.146). The authors used structural MRI scans to predict the ages of participants with epilepsy and their healthy peers. A machine learning algorithm was used to predict age, based on data from healthy patients that had been gathered from large, publicly available imaging databases.

The difference between predicted brain age and chronological age was on average 8.8 years older for patients with uncontrolled epilepsy than healthy participants.

"The absence of similar changes in patients with new-onset epilepsy suggests that ongoing seizures may underlie the brain aging phenomenon observed in this study. This technique could potentially be used to identify individuals with intractable epilepsy early in the course of their disease, and may also be useful for other applications like measuring the protective effect of antiepileptic medication." said Heath Pardoe, Ph.D., an assistant professor of neurology at New York University Langone Medical Center.

A second study, led by researchers at the University of Turku, reveals the fate of children with epilepsy 50 years later. The researchers followed 179 individuals with childhood-onset epilepsy from childhood to old age using neuropsychological assessments and multimodality imaging techniques to gain insights into the aging process. An analysis of the participants' survival, seizure outcomes, social integration and reproductive activity seems promising: Most of the participants achieved 10-year remission without medications, and most of those without comorbid illnesses graduated from school, obtained driver's licenses and achieved a socioeconomic status comparable with healthy controls. Although the researchers note that fewer participants with epilepsy live in partnership and have children compared with healthy participants, both groups appear to enjoy a high quality of life.

"Despite having excellent seizure outcomes, the subjects proved to have abnormal neurologic signs, including markers of cerebrovascular disease. This is an excellent opportunity to show, in further follow-up investigations, whether or not the markers of cerebrovascular diseases predict future stroke and cognitive impairment," said author Matti Sillanpää, M.D., Ph.D., a professor and senior research scientist at the University of Turku, Finland.

The third study, conducted at the University of Eastern Finland, is the first of its kind to link traumatic brain injury (TBI) with post-traumatic epilepsy (PTE) in the aging population, particularly in elderly people carrying risk genes for Alzheimer's disease (AD).

In a study in mice, researchers explored whether TBI increases risk for the development of epilepsy, called epileptogenesis, in those genetically at risk for Alzheimer's. They found that the combination of TBI and genetic risk for Alzheimer's not only resulted in epileptogenesis, but also some somatomotor and cognitive impairments. The study is the first of its kind to provide comprehensive evidence that TBI in those with a genetic risk for familial AD can result in exacerbated epileptogenesis and its molecular mechanisms.

"This study will help improve the quality of life of the elderly community by being able to identify risk factors associated with TBI and AD," said Asla Pitkänen, M.D., Ph.D., D.Sc., director of the department of neurobiology at the University of Eastern Finland. "By arming family members, caregivers and retirement communities with this information before a fall, we hope to put them on alert so preventative measures can be taken to prevent injury and post-traumatic epilepsy."

The fourth and final study, conducted by researchers at Dalhousie University in Halifax, compared patients who had their first seizure in their sixth decade with patients who had seizures in their seventh decade or later to determine if the widely used term "epilepsy in the elderly" (EE) is an oversimplification. Seizure dynamics, MRI lesions, EEG findings and treatment course in elderly and middle-aged (MAE) patients were studied in both groups. EE and MAE patients showed similar variability with regard to imaging findings such as microangiopathy, infarcts, atrophy, tumors, vascular malformations and other pathologies. In addition, there was no significant difference between seizure dynamics, EEG findings and overall excellent treatment prognosis in both groups.

"We had postulated that 'epilepsy in the elderly' was conceptually irrelevant and would need to be replaced by a cause-driven sophisticated classification system in the aging brain," said Bernd Pohlmann-Eden M.D. Ph.D., a professor in the division of neurology, department of pharmacology and department of psychology and neuroscience at Dalhousie University. "However, our small group data comparison trial confirms that our understanding in which way individually documented MRI findings in the aging brain predispose to seizure recurrence is currently entirely speculative."

https://www.sciencedaily.com/releases/2015/12/151207145859.htm