By Ganesh M. Babulal, PhD
Accompanying hallmark cognitive impairments of symptomatic Alzheimer's disease (AD), mood disorders like depression, apathy, or anxiety are common comorbid conditions. Additionally, mood disorders in symptomatic AD are associated with poorer cognitive functioning, higher functional impairment, and faster physical decline, which may require placement into assisted care for AD patients. Preclinical AD is the long period preceding symptomatic AD and is defined as cognitive normality with positive biomarker evidence that the disease process has started—this area has received much attention and emphasis in recent years. Furthermore, research focus is shifting to examine noncognitive outcomes like mood to better understand the pathophysiological progression of the disease and related outcomes. The preclinical AD and mood literature has a proclivity to examine singular, negative mood states like depression or anxiety.
In a recent study published in the American Journal of Geriatric Psychiatry, Babulal and colleagues examined the relationship between global measures of mood disturbances (positive and negative states), cognitive function, and AD biomarkers. Mood was assessed across three different measures: the Profile of Mood States—Short Form (POMS-SF), the Geriatric Depression Scale short form (GDS), and the Neuropsychiatric Inventory Questionnaire (NPI-Q). The study sample was a subset of the Knight Alzheimer’s Disease Research Center (ADRC) cohort enrolled in an affiliated study assessing preclinical AD and driving performance. All participants had to be cognitively normal as determined by a 0 on the Clinical Dementia Rating Scale and took part in PET amyloid imaging using Pittsburgh Compound B (PiB) tracer and a lumbar puncture for collection of cerebrospinal fluid (CSF). Six AD biomarkers were analyzed: β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42, and the mean cortical binding potential [MCBP] for PET-PiB. The study examined the relationship between mood and the biomarkers at baseline and follow-up at 1 year, while controlling for age, gender, and years of education.
At baseline, there were no relationships between the different measures of mood and the six biomarkers. However, in the longitudinal follow up, participants with higher values of CSF ratio biomarker tau/Aβ42 had greater change in their total mood disturbance score on the POMS-SF compared to those with lower biomarker values. The tau/Aβ42 ratio also predicted greater change in negative emotions of depression, anxiety, and confusion. Furthermore, there was greater change in anger, depression (GDS), and neuropsychiatric symptoms (NPI-Q) for persons with higher biomarker levels as reflected by MCBP for PET-PiB values. Most importantly, there was no change in cognitive functioning as measured by both dementia screenings and neuropsychological memory tasks from baseline to follow up. Further, there was no correlation between the mood measures and the neuropsychological tasks or dementia screens.
The findings of this study highlight that CSF and PET-PiB biomarkers predict mood changes in cognitively normal older adults. Variables reflecting combinations of biomarkers (CSF tau/Aβ42) may be better predictors of decline in noncognitive outcomes such as mood, compared to individual biomarkers. Negative mood changes seem to occur earlier preceding changes in cognitive function in participants who have positive biomarker evidence. Finally, these findings support the utility of AD biomarkers in examining changes in noncognitive outcomes like mood.
Funding Acknowledgment
Dr. Babulal kindly acknowledges research support from the NIH’s National Institute on Aging (NIA) (R01AG043434; R01AG043434-03S1) and a University Research Strategic Alliance grant from Washington University in St. Louis (URSA #2016).
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Mood Changes in Cognitively Normal Older Adults Are Linked to Alzheimer's Disease Biomarker Levels
About the Author
Ganesh M. Babulal is a post-doctoral research associate in the Department of Neurology and Knight Alzheimer’s Disease Research Center at Washington University School of Medicine in St. Louis. His research interests lie in investigating the relationship between cognition and mental health and its impact on instrumental activities of daily living in populations with chronic neurological diseases. Dr. Babulal is currently working on two NIH/NIA-funded studies: (1) evaluating the relationship between biomarkers of preclinical Alzheimer’s disease and driving performance and (2) development of a naturalistic driving methodology to examine daily driving behavior outcomes in cognitively normal older adults.
