Disentangling the relationship of subjective cognitive decline and depressive symptoms in the development of cognitive decline and dementia

Kleineidam, Luca; Wagner, Michael; Guski, Jannis; Wolfsgruber, Steffen; Miebach, Lisa; Bickel, Horst; König, Hans‐Helmut; Weyerer, Siegfried; Lühmann, Dagmar; Kaduszkiewicz, Hanna; Luppa, Melanie; Röhr, Susanne; Pentzek, Michael; Wiese, Birgitt; Maier, Wolfgang; Scherer, Martin; Kornhuber, Johannes; Peters, Oliver; Frölich, Lutz; Wiltfang, Jens; Lewczuk, Piotr; Hüll, Michael; Ramı́rez, Alfredo; Jessen, Frank; Riedel‐Heller, Steffi G.; Heser, Kathrin

doi:10.1002/alz.12785

Cited by 11 publications

(8 citation statements)

References 62 publications

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“…Kleineidam et al. ( 35 ) reported that subjective cognitive decline precedes depressive symptoms in the development of dementia.…”

Section: Discussionmentioning

confidence: 99%

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study

Luppa,

Pabst,

Löbner

et al. 2024

Front. Psychiatry

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PurposeThe present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups.MethodsData were derived from a prospective multicenter cohort study conducted in primary care – the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up. To assess depressive symptoms, the short version of the Geriatric Depression Scale (GDS-15, cutoff score 6) was used. Age-specific competing risk regressions were performed to analyze risk factors for incident depressive symptoms in different age groups (75 to 79, 80 to 84, 85+ years), taking into account the accumulated mortality.ResultsThe age-specific incidence rate of depression was 33 (95% CI 29-38), 46 (95% CI 40-52) and 63 (95% CI 45-87) per 1,000 person years for the initial age groups 75 to 79, 80 to 84 and 85+ years, respectively. In competing risk regression models, female sex, mobility as well as vision impairment, and subjective cognitive decline (SCD) were found to be risk factors for incident depression for age group 75 to 79, female sex, single/separated marital status, mobility as well as hearing impairment, and SCD for age group 80 to 84, and mobility impairment for age group 85+.ConclusionDepressive symptoms in latest life are common and the incidence increases with increasing age. Modifiable and differing risk factors across the highest age groups open up the possibility of specifically tailored prevention concepts.

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“…Kleineidam et al. ( 35 ) reported that subjective cognitive decline precedes depressive symptoms in the development of dementia.…”

Section: Discussionmentioning

confidence: 99%

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study

Luppa,

Pabst,

Löbner

et al. 2024

Front. Psychiatry

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“…However, our data now raise the possibility that the combination of an assessment of SCD with cognitive testing could offer a suitable approach to identify high-risk groups for clinical progression. Research on the combination of SCD and MNPD with the assessment of depressive symptoms 34 or broader neuropsychiatric concepts, such as mild behavioral impairment, 35 may further promote the identification of clinical phenotypes of AD that precede the onset of MCI.…”

Section: Discussionmentioning

confidence: 99%

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Stark,

Wolfsgruber,

Kleineidam

et al. 2023

Neurology

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Background and Objectives:To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer’s disease (AD) biomarkers, cognitive decline and clinical progression to mild cognitive impairment (MCI).Methods:This study included clinical SCD patients and SCD free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observationalDZNE Longitudinal Cognitive Impairment and Dementia(DELCODE) study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from theConsortium to Establish a Registry for Alzheimer’s DiseaseNeuropsychological Assessment Battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181),total tau and Aβ42/p-tau181levels, longitudinal cognitive composite trajectories and risk of clinical progression to incident MCI (follow-upM±SD: 40.6±23.7 months). Additionally, we explored group differences between SCD and HC in those without MNPD.Results:In our sample (N = 672, mean age: 70.7±5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline and a higher risk of progression to incident MCI (HR: 4.07, 95%CI: 2.46-6.74) compared to SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95%CI: 38.5-75.4) and a negative predictive value of 86.0% (95%CI: 81.9-90.1) for the progression of SCD to MCI within three years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared to HC participants without MNPD (n = 215; HR: 4.09, 95%CI: 2.07-8.09), while AD biomarker levels did not differ significantly between these groups.Discussion:Our results suggest that MNPD are a risk factor for AD related clinical progression in cognitively normal patients seeking medical counseling due to SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD.

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“…In this study, using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), several NPS profiles exhibited different ratios of conversion to dementia but no association with the CSF AD-core biomarker status. However, a recent cross-sectional study [ 20 ] using a large sample of community-dwelling individuals reported that CSF Aβ42, T-tau/Aβ42 and p-tau/Aβ42 levels were associated with depression, and a prospective study including subjective cognitive decline (SCD) participants of the German Dementia Competence Network (DCN) study, CSF Aβ42 was found associated with an increment in depression severity over time [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment

Marquié

García‐Gutiérrez

Orellana

et al. 2023

IJMS

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Few studies have addressed the impact of the association between Alzheimer´s disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

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Disentangling the relationship of subjective cognitive decline and depressive symptoms in the development of cognitive decline and dementia

Cited by 11 publications

References 62 publications

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment

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