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

Amyloid is a less accurate marker for measuring severity, progression of Alzheimer's

August 6, 2019

Science Daily/University of Pennsylvania School of Medicine

Researchers find fluorodeoxyglucose (FDG) PET is a better indicator of cognitive performance when compared to PET scans that detect amyloid protein.

While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimer's disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brain's glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimer's and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain. This suggests that FDG-PET is also a better means for determining the effectiveness of Alzheimer's therapies, as well as tracking patients' disease advancement, in both clinical and research settings. Results of this study are detailed in the August issue of the Journal of Alzheimer's Disease.

"Both florbetapir-PET and FDG-PET are approved diagnostic methods for Alzheimer's disease, and both appear to be effective in indicating some sort of cognitive impairment. However, we have now shown that FDG-PET is significantly more precise in clinical studies, and it is also available for routine use with modest costs," said the study's co-principal investigator Abass Alavi, MD, PhD, a professor of Radiology at Penn. "Our results support the notion that amyloid imaging does not reflect levels of brain function, and therefore it may be of limited value for assessing patients with cognitive decline."

Alzheimer's disease, the most common cause of dementia, is the sixth leading cause of death in the United States, affecting up to 5.8 million Americans currently. As clinicians aim to spot and treat the symptoms of dementia in its earliest stages, PET plays an increasingly pivotal role in diagnosing and monitoring Alzheimer's disease, as well as MCI, a condition that often precedes dementia.

Two of the most significant biomarkers found in Alzheimer's are decreased glucose uptake and the accumulation of amyloid plaques in the brain. PET scans use different radioactive drugs, called radiotracers, to measure these biomarkers within the brain tissue of patients with cognitive impairment. FDG-PET is one of the most commonly used imaging techniques to diagnose Alzheimer's. However, in recent years, several other radiotracers, such as florbetapir, have been developed to detect the deposition of amyloid plaques.

Recently, the effectiveness of amyloid imaging as a strategy for monitoring dementia symptoms has been called into question. While the presence of amyloid plaques in the brain is considered as being characteristic of Alzheimer's, some studies have shown that large amounts of amyloid plaques were present in healthy, non-demented individuals. Conversely, recent clinical trials have shown that the intended removal of amyloid from the brains of patients with Alzheimer's disease led to no change in, or even worsened, cognitive performance.

In this study, the researchers evaluated 63 individuals, including 19 with clinically diagnosed Alzheimer's disease, 23 with MCI, and 21 healthy individuals. The study participants underwent both FDG- and florbetapir-PET imaging. They were then assessed with a Mini Mental Status Examination (MMSE), a widely used diagnostic test for detecting and assessing the severity of cognitive impairment. The researchers used a novel "global quantification approach" to generate data from five different regions of the brain, which were correlated with the results from the MMSE scores.

The study revealed that both FDG- and florbetapir-PET scans are able to effectively discriminate the individuals with dementia from the healthy control group. However, when compared with the MMSE scores, the correlation between low cognitive performance and high levels of amyloid was significantly weaker than the correlation between FDG and low cognitive performance for all groups included in the study. This suggests that FDG-PET is a more sensitive indicator of cognitive decline.

"Amyloid imaging has a value in diagnosing or ruling out Alzheimer's disease, but it's a bit like all or nothing. Our study shows that it can reveal disease, but you wouldn't be able to differentiate between someone who had very mild or very severe symptoms," said co-principal investigator Andrew Newberg, MD, a professor of Radiology at Thomas Jefferson University, who added that these findings have important implications for clinical research.

"In a clinical drug trial, for example, it may be more relevant to do an FDG-PET scan, rather than using amyloid as a marker, to find out whether the therapy is working," Newberg said.

While FDG-PET may not be a perfect diagnostic tool, the study confirms that currently it is the best available method for monitoring symptoms of dementia, according to Alavi.

"Right now, FDG is king when it comes to looking at brain function, not only in Alzheimer's disease, but also diseases like vascular dementia and cancer," Alavi said.

https://www.sciencedaily.com/releases/2019/08/190806121133.htm