scholarly journals Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gwenn S. Smith ◽  
Clifford I. Workman ◽  
Hillary Protas ◽  
Yi Su ◽  
Alena Savonenko ◽  
...  

AbstractDepression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems. Informed by these preclinical data, the hypotheses were tested that a spatial covariance pattern of higher beta-amyloid (Aβ) and lower serotonin transporter availability (5-HTT) in frontal, temporal, and parietal cortical regions would distinguish LLD patients from healthy controls and the expression of this pattern would be associated with greater depressive symptoms. Twenty un-medicated LLD patients who met DSM-V criteria for major depression and 20 healthy controls underwent PET imaging with radiotracers for Aβ ([11C]-PiB) and 5-HTT ([11C]-DASB). A voxel-based multi-modal partial least squares (mmPLS) algorithm was applied to the parametric PET images to determine the spatial covariance pattern between the two radiotracers. A spatial covariance pattern was identified, including higher Aβ in temporal, parietal and occipital cortices associated with lower 5-HTT in putamen, thalamus, amygdala, hippocampus and raphe nuclei (dorsal, medial and pontine), which distinguished LLD patients from controls. Greater expression of this pattern, reflected in summary 5-HTT/Aβ mmPLS subject scores, was associated with higher levels of depressive symptoms. The mmPLS method is a powerful approach to evaluate the synaptic changes associated with AD pathology. This spatial covariance pattern should be evaluated further to determine whether it represents a biological marker of antidepressant treatment response and/or cognitive decline in LLD patients.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 480-480
Author(s):  
Danielle Powell ◽  
Willa Brenowitz ◽  
Kristine Yaffe ◽  
Frank Lin ◽  
Alden Gross ◽  
...  

Abstract Late-life depression is a comorbidity which may co-occur in older adults with hearing loss- each as prevalent and independent modifiable risk factors for dementia. We used data from 1,820 participants (74 ± 2.8 years, 38% Black race) from the Health Aging and Body Composition Study to test if the hearing loss-dementia/cognitive decline (Modified Mini Mental State Exam[3MS] and Digit Symbol Substitution[DSST]) relationship differed in hearing impaired participants who also had depressive symptoms. Depressive symptoms were defined as CES-D 10 ≥10) at one or more visits from years 1-5. Algorithmic incident dementia defined using medication use, hospitalizations and cognitive test scores. Audiometric hearing loss was measured at year 5 and categorized as normal/mild vs ≥moderate loss. In linear mixed models adjusted for demographic and clinical covariates, presence of both hearing loss and depressive symptoms (vs. having neither) was associated with faster rates of decline in 3MS (-0.30, 95% CI:-0.78, -0.19) and DSST (-0.35,95% CI:-0.67, -0.03) over 10 years of follow-up. Both hearing loss and depressive symptoms (vs. neither) was associated with increased risk (hazard ratio (HR):2.91, 95%CI: 1.59, 5.33) of incident dementia in multivariable-adjusted Cox proportional hazards models. Comorbid conditions among hearing impaired older adults should be considered and may aid in dementia prevention and management strategies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Ly ◽  
H. T. Karim ◽  
J. T. Becker ◽  
O. L. Lopez ◽  
S. J. Anderson ◽  
...  

AbstractLate-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.


2014 ◽  
Vol 27 (5) ◽  
pp. 707-714 ◽  
Author(s):  
Meghan Riddle ◽  
Douglas R. McQuoid ◽  
Guy G. Potter ◽  
David C. Steffens ◽  
Warren D. Taylor

ABSTRACTBackground:Depression in late life is a risk factor for cognitive decline. Depression is also associated with increased disability and social support deficits; these may precede conversion to dementia and inform risk. In this study, we examined if baseline or one-year change in disability and social support predicted later cognitive deterioration.Methods:299 cognitively intact depressed older adults were followed for an average of approximately seven years. Participants received antidepressant treatment according to a standardized algorithm. Neuropsychological testing and assessment of disability and social support were assessed annually. Cognitive diagnosis was reviewed annually at a consensus conference to determine if participants remained cognitively normal, or if they progressed to either dementia or cognitively impaired, no dementia (CIND).Results:During study participation, 167 individuals remained cognitively normal (56%), 83 progressed to CIND (28%), and 49 progressed to dementia (16%). Greater baseline instrumental activities of daily living (IADL) deficits predicted subsequent conversion to a cognitive diagnosis (CIND or dementia). However, neither baseline measures nor one-year change in basic ADLs (BADLs) and social support predicted cognitive conversion. In post hoc analyses, two IADL measures (managing finances, preparing meals) significantly increased the odds of cognitive conversion.Conclusions:Greater IADL deficits predicted increased risk of cognitive conversion. Assessment of IADL deficits may provide clues about risk of later cognitive decline.


2016 ◽  
Vol 33 (S1) ◽  
pp. S382-S382 ◽  
Author(s):  
S. Petrykiv ◽  
M. Arts ◽  
L. de Jonge

IntroductionOlder adults with adrenocortical insufficiency, including Addison's disease (AD), are at an increased risk for developing late-life depression. Treatment of AD with glucocorticoid replacement therapy may exacerbate depressive symptoms and may complicate treatment of late-life depression.ObjectivesTo present a case with algorithm of decision-making in a particular case of glucocorticoid induced depression in patient with syndrome of Addison.AimsTo report a case-study, describing treatment of Addison's disease in LLD.MethodsA case report is presented and discussed, followed by a literature review.ResultsA 77-year-old female, diagnosed with Addison's disease, was referred with persistent fatigue, weakness, weight loss, sleep disturbances, and depressive symptoms over the previous 6 months. She was taken losartan 100 mg/day, zolpidem 10 mg/day, fludrocortisone 100 μg/day, and hydrocortisone 35 mg/day. There was no personal or family history of psychiatric problems. Clinical examination was normal aside from skin hyperpigmentation. After initial minimal dose reduction of glucocorticoids, Addison's disease remained under control. One week later, her depressive symptoms disappeared without administration of antidepressants.ConclusionThe association between glucocorticoid replacement therapy and late-life depression is not well understood. The current case shows that treatment of glucocorticoid-induced depression in subjects with Addison's disease is achievable by minimal adjustments in glucocorticoid regiment. However, collaboration with endocrinology is of vital importance to prevent an Addison's crisis. Pharmacokinetic dose-finding studies are required to find optimal glucocorticoid adjustment strategy.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2021 ◽  
Vol 30 ◽  
Author(s):  
Shiyu Lu ◽  
Tianyin Liu ◽  
Gloria H. Y. Wong ◽  
Dara K. Y. Leung ◽  
Lesley C. Y. Sze ◽  
...  

Abstract Aims Late-life depression has substantial impacts on individuals, families and society. Knowledge gaps remain in estimating the economic impacts associated with late-life depression by symptom severity, which has implications for resource prioritisation and research design (such as in modelling). This study examined the incremental health and social care expenditure of depressive symptoms by severity. Methods We analysed data collected from 2707 older adults aged 60 years and over in Hong Kong. The Patient Health Questionnaire-9 (PHQ-9) and the Client Service Receipt Inventory were used, respectively, to measure depressive symptoms and service utilisation as a basis for calculating care expenditure. Two-part models were used to estimate the incremental expenditure associated with symptom severity over 1 year. Results The average PHQ-9 score was 6.3 (standard deviation, s.d. = 4.0). The percentages of respondents with mild, moderate and moderately severe symptoms and non-depressed were 51.8%, 13.5%, 3.7% and 31.0%, respectively. Overall, the moderately severe group generated the largest average incremental expenditure (US$5886; 95% CI 1126–10 647 or a 272% increase), followed by the mild group (US$3849; 95% CI 2520–5177 or a 176% increase) and the moderate group (US$1843; 95% CI 854–2831, or 85% increase). Non-psychiatric healthcare was the main cost component in a mild symptom group, after controlling for other chronic conditions and covariates. The average incremental association between PHQ-9 score and overall care expenditure peaked at PHQ-9 score of 4 (US$691; 95% CI 444–939), then gradually fell to negative between scores of 12 (US$ - 35; 95% CI - 530 to 460) and 19 (US$ -171; 95% CI - 417 to 76) and soared to positive and rebounded at the score of 23 (US$601; 95% CI -1652 to 2854). Conclusions The association between depressive symptoms and care expenditure is stronger among older adults with mild and moderately severe symptoms. Older adults with the same symptom severity have different care utilisation and expenditure patterns. Non-psychiatric healthcare is the major cost element. These findings inform ways to optimise policy efforts to improve the financial sustainability of health and long-term care systems, including the involvement of primary care physicians and other geriatric healthcare providers in preventing and treating depression among older adults and related budgeting and accounting issues across services.


2014 ◽  
Vol 26 (9) ◽  
pp. 1501-1509 ◽  
Author(s):  
Celia F. Hybels ◽  
Carl F. Pieper ◽  
Lawrence R. Landerman ◽  
Martha E. Payne ◽  
David C. Steffens

ABSTRACTBackground:The association between disability and depression is complex, with disability well established as a correlate and consequence of late life depression. Studies in community samples report that greater volumes of cerebral white matter hyperintensities (WMHs) seen on brain imaging are linked with functional impairment. These vascular changes are also associated with late life depression, but it is not known if depression is a modifier in the relationship between cerebrovascular changes and functional impairment.Methods:The study sample was 237 older adults diagnosed with major depression and 140 never depressed comparison adults, with both groups assessed at study enrollment. The dependent variable was the number of limitations in basic activities of daily living (ADL), instrumental ADLs, and mobility tasks. The independent variable was the total volume of cerebral white matter lesions or hyperintensities assessed though magnetic resonance imaging.Results:In analyses controlling for age, sex, race, high blood pressure, and cognitive status, a greater volume of WMH was positively associated with the total number of functional limitations as well as the number of mobility limitations among those older adults with late life depression but not among those never depressed, suggesting the association between WMH volume and functional status differs in the presence of late life depression.Conclusions:These findings suggest older patients with both depression and vascular risk factors may be at an increased risk for functional decline, and may benefit from management of both cerebrovascular risk factors and depression.


2006 ◽  
Vol 63 (2) ◽  
pp. 153 ◽  
Author(s):  
Mary Ganguli ◽  
Yangchun Du ◽  
Hiroko H. Dodge ◽  
Graham G. Ratcliff ◽  
Chung-Chou H. Chang

2014 ◽  
Vol 20 (5) ◽  
pp. 461-467 ◽  
Author(s):  
Aaron M. Koenig ◽  
Rishi K. Bhalla ◽  
Meryl A. Butters

AbstractThis brief report provides an introduction to the topic of cognitive functioning in late-life depression (LLD). In addition to providing a review of the literature, we present a framework for understanding the heterogeneity of cognitive outcomes in this highly prevalent disorder. In addition, we discuss the relationship between LLD and dementia, and highlight the importance of regularly assessing cognitive functioning in older adults who present with depressive symptoms. If cognitive deficits are discovered during a neuropsychological assessment, we recommend referral to a geriatric psychiatrist or cognitive neurologist, for evaluation and treatment of the patient’s symptoms. (JINS, 2014, 20, 1–7)


2016 ◽  
Vol 47 (4) ◽  
pp. 690-702 ◽  
Author(s):  
A. Brailean ◽  
M. J. Aartsen ◽  
G. Muniz-Terrera ◽  
M. Prince ◽  
A. M. Prina ◽  
...  

BackgroundCognitive impairment and depression often co-occur in older adults, but it is not clear whether depression is a risk factor for cognitive decline, a psychological reaction to cognitive decline, or whether changes in depressive symptoms correlate with changes in cognitive performance over time. The co-morbid manifestation of depression and cognitive impairment may reflect either a causal effect or a common cause, depending on the specific symptoms experienced and the cognitive functions affected.MethodThe study sample comprised 1506 community-dwelling older adults aged ⩾65 years from the Longitudinal Aging Study Amsterdam (LASA). We conducted cross-domain latent growth curve analyses to examine longitudinal associations between late-life depression dimensions (i.e. depressed affect, positive affect, and somatic symptoms) and specific domains of cognitive functioning (i.e. processing speed, inductive reasoning, immediate recall, and delayed recall).ResultsPoorer delayed recall performance at baseline predicted a steeper increase in depressed affect over time. Steeper decline in processing speed correlated with a steeper increase in somatic symptoms of depression over time.ConclusionsOur findings suggest a prospective association between memory function and depressed affect, whereby older adults may experience an increase in depressed affect in reaction to poor memory function. Somatic symptoms of depression increased concurrently with declining processing speed, which may reflect common neurodegenerative processes. Our findings do not support the hypothesis that depression symptoms may be a risk factor for cognitive decline in the general population. These findings have potential implications for the treatment of late-life depression and for the prognosis of cognitive outcomes.


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