Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer’s Disease Pathology and Cognitive Decline

Johansson, Maurits; Stomrud, Erik; Johansson, Per; Svenningsson, Anna; Palmqvist, Sebastian; Janelidze, Shorena; Westen, Danielle van; Mattsson‐Carlgren, Niklas; Hansson, Oskar

doi:10.1016/j.biopsych.2022.01.012

Cited by 34 publications

(23 citation statements)

References 57 publications

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“…For NHWs, total GDS and Dysphoria scores were related to Aβ40, a marker of amyloid burden. Apathy which was found to be related to Aβ pathology in the early stage of Alzheimer's in a Swedish study 35 was not be related either marker of amyloid in our cohort. When the level of depression as measured by the number of GDS items endorsed is analyzed for the total sample, those defined as depressed had higher levels of Aβ40, Aβ42 and NfL.…”

Section: Discussioncontrasting

confidence: 64%

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Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression

Hall

Petersen

Johnson

et al. 2023

MRAJ

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Background: Depression is both a risk factor for and early symptom of Alzheimer’s disease. Numerous studies have investigated the relationship between AT(N) biomarkers of AD and depression; however, the majority of these have utilized CSF in Non-Hispanic White populations. Objective: To investigate the relationship between plasma total Tau, Aβ40, Aβ42, NFL and depression in Mexican-Americans and Non-Hispanic Whites. Methods: The study was a cross-sectional comparison of 645 Mexican American and 644 Non-Hispanic White older adults in a community-based study of cognitive aging who had been categorized as having unimpaired cognition using a consensus based algorithmic approach. Plasma biomarkers were assayed using Simoa technology. The Geriatric Depression Scale assessed depression. Results: Mexican Americans had significantly higher scores on the GDS. Non-Hispanic Whites had higher Aβ40, and Aβ42 and MAs had higher NFL and Tau. For Mexican Americans, linear regression analyses found NfL and Aβ42 significant predictors of GDS scores whereas for the Non-Hispanic White group none of the biomarkers was significantly related to GDS total score or any of the subscale scores. Those scoring in the depressed range had significantly higher levels of Aβ40, Aβ42, and NFL. When analyzed by ethnicity the depressed Mexican Americans had significantly higher levels of Aβ40, Aβ42, and NFL than the non-depressed. No difference between the depression levels on any of the biomarkers was found for Non-Hispanic Whites. Conclusions: Findings support the importance of evaluating the effect of ethnicity and level of depressive symptoms when assessing the relationship of AD biomarkers to depression. In cognitively unimpaired MAs depression is related to the Alzheimer’s Disease biomarkers but this is not the case for Non-Hispanic Whites. Higher levels of these biomarkers among depressed cognitively unimpaired Mexican Americans may be an indicator of increased risk for cognitive impairment but not for Non-Hispanic Whites. Longitudinal research is needed to clarify the effect of ethnicity on the biomarker-depression relationship.

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Section: Discussioncontrasting

confidence: 64%

“…A follow up study looking at additional CSF biomarkers found the depressed individuals had higher levels of Aβ42 and NFL. 14 Johansson et al 15 in a study of cognitively unimpaired older Swedes; found that CSF amyloid-β pathology predicted levels of apathy longitudinally.…”

Section: Introductionmentioning

confidence: 99%

Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression

Hall

Petersen

Johnson

et al. 2023

MRAJ

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“…There has been evidence showing that Neuropsychiatric Symptoms (NPSs), such as anxiety, apathy and irritability, are often associated with cortical damage of temporal lobe, middle frontal gyrus and limbic system in AD patients [19]. Aβ sedimentation is an important driving factor for the development of apathy and anxiety in the aged [20]. The frequency and severity of NPS may increase along with the deterioration of cognitive ability [21].…”

Section: Discussionmentioning

confidence: 99%

BI-D1870 Causes the Rats’ Learning and Memory Acquisition Ability Impairment

Zhang¹,

He²,

Li³

et al. 2023

JBM

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Aim: To observe the rats' learning and memory acquisition ability disturbance induced by BI-D1870. Methods: Male SD rats were randomly divided into control group, solvent control group and BI-D1870 group. The rats in the control group were intraperitoneally injected with saline, while those in the solvent control group were intraperitoneally injected with DMSO + sulfobutyl-β-cyclodextrin solvent, and those in the BI-D1870 group were intraperitoneally injected with BI-D1870. All the rats' appearance and behavior were daily observed, and body weight was recorded on the day 15, 30, 45, 60, 75 and 82 of BI-D1870 injected. Morris water maze was used to screen the rats' learning and memory acquisition ability on the day 22 -25, 52 -55, and 82 -85 of training by BI-D1870 treated. The successful rates of the rats' memory impairment were respectively calculated for three times screening. Results: During the whole experiment, there was no obvious difference in appearance and fur color in all rats. The rats' agitation began to appear on the day 10 th of BI-D1870 given. The agitation rats' number and rats' body weight gradually increased along with BI-D1870 treated (P < 0.05, P < 0.01). According to the latency of rats on the day 25, 55 and 85 in Morris water maze training, the rats' successful rate in the learning and memory acquisition ability impairment induced by BI-D1870 was 50.00%, 62.00% and 82.00%, respectively. Conclusion: Intraperitoneal injection of BI-D1870 can induce the rats' learning and memory acquisition ability disorder.

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“…With regard to amyloid‐PET imaging, most cross‐sectional studies reported associations between higher neuropsychiatric symptoms burden and higher amyloid load, 9–11,50,51 albeit some studies did not confirm this association 52,53 . Longitudinal studies also provided evidence of associations between neuropsychiatric symptoms, amyloid deposition, and cognitive decline, 54–56 and between abnormal amyloid deposition and higher neuropsychiatric symptoms over time 57–59 . With regard to tau‐PET imaging, one cross‐sectional study revealed significant associations between higher depressive symptoms with greater inferior temporal and entorhinal cortex tau in cognitively unimpaired older adults, 12 whereas another study showed that neuropsychiatric symptoms were associated with tau‐PET in the parietal association area, superior frontal, temporal, and medial occipital lobes 13 …”

Section: Discussionmentioning

confidence: 99%

Plasma‐derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms: A community‐based study

Krell‐Roesch,

Zaniletti,

Syrjanen

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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INTRODUCTIONWe examined associations between plasma‐derived biomarkers of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS) in community‐dwelling older adults.METHODSCross‐sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma‐derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p‐tau181], p‐tau217, total tau [t‐tau], neurofilament light [NfL]), and NPS assessment.RESULTSP‐tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41–3.00, p < 0.001), p‐tau217 (OR 1.70, 95% CI 1.10–2.61, p = 0.016), and t‐tau (OR 1.44, 95% CI 1.08–1.92, p = 0.012) were associated with appetite change. We also found that p‐tau181 and p‐tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20–3.11, p = 0.007 and OR 2.04, 95% CI 1.21–3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45–3.93, p = 0.001 and OR 2.30, 95% CI 1.33–3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS.CONCLUSIONHigher plasma‐derived p‐tau181 and p‐tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment.HIGHLIGHTS We studied 1005 community‐dwelling persons aged ≥ 50 years Higher plasma tau levels are associated with increased neuropsychiatric symptoms Aβ42/Aβ40 and NfL are not associated with neuropsychiatric symptoms Clinicians should treat neuropsychiatric symptoms in persons with high plasma‐derived tau

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Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer’s Disease Pathology and Cognitive Decline

Cited by 34 publications

References 57 publications

Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression

Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression

BI-D1870 Causes the Rats’ Learning and Memory Acquisition Ability Impairment

Plasma‐derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms: A community‐based study

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