Differential Risk of Incident Alzheimer’s Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline

Wolfsgruber, Steffen; Kleineidam, Luca; Wagner, Michael; Mösch, Edelgard; Bickel, Horst; Lühmann, Dagmar; Ernst, Andrej; Wiese, Birgitt; Steinmann, Susanne; König, Hans‐Helmut; Brettschneider, Christian; Luck, Tobias; Stein, Janine; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Ângela; Maier, Wolfgang; Scherer, Martin; Riedel‐Heller, Steffi G.; Jessen, Frank

doi:10.3233/jad-160407

Cited by 73 publications

(73 citation statements)

References 41 publications

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“…The findings are consistent with recent literature on the relevance of longitudinal assessment of SCD in identifying individuals at high risk of neurocognitive disorders. In particular, the presence of Persistent SCD over time has consistently been highlighted in recent literature as a key predictor of incident neurocognitive disorders [ 44 – 46 ]. This finding is understandable, given that neurocognitive disorders are conceptualized as progressive neurodegenerative diseases, and hence in the face of progressive neuropathological processes, individuals are more likely to experience persistent rather than transient symptoms of SCD [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia

Liew

2020

Alz Res Therapy

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Background In cognitively normal individuals, subjective cognitive decline (SCD) has been reported to predict MCI and dementia (MCI/dementia). However, prior studies mostly captured SCD at single time-points without considering the longitudinal course of SCD. This study examined whether the trajectories of SCD provide any added information—beyond one-time assessments of SCD—on the risk of MCI/dementia. Methods This cohort study included 5661 participants from the Alzheimer’s Disease Centers across the USA, who were ≥ 50 years and had normal cognition in the first-four annual visits (year 1 to year 4). The participants were evaluated for SCD in the first-four annual visits (year 1 to year 4), and followed-up almost annually (year 4 up to year 14) for incident MCI/dementia. SCD trajectories (as identified from latent-class-growth-curve-analysis) were included in Cox regression to estimate their risks of MCI/dementia, with analyses further stratified by age (< 75 years versus ≥ 75 years; based on median-split). Results Compared to those without SCD (in the first-four annual visits), Intermittent SCD (i.e., reported in 1–2 of the first-four annual visits) predicted a higher risk (HR 1.4) and Persistent SCD (i.e., reported in 3–4 of the first-four annual visits) predicted the highest risk (HR 2.2), with the results remaining significant even after adjusting for baseline SCD. Age-stratified analysis revealed that the risk associated with Intermittent SCD was only present in older individuals, while risk related to Persistent SCD was consistently present across the younger and older age groups. Age compounded the effects of the trajectories, whereby older individuals with Persistent SCD had > 75% probability of developing MCI/dementia by 10 years, in contrast to < 25% probability by 10 years in younger individuals with No SCD. Conclusions The findings demonstrate the utility of SCD trajectories—especially when used in combination with age strata—in identifying high-risk populations for preventive interventions and trials. They also suggest a potential modification in the current SCD criteria, with the inclusion of “persistent SCD over several years” as a feature of SCD plus.

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Section: Discussionmentioning

confidence: 99%

Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia

Liew

2020

Alz Res Therapy

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“…[201][202][203] One study showed those who over time consistently reported subjective cognitive decline that they found worrisome were at higher risk for developing Alzheimer's dementia. 204 The Behavioral Risk Factor Surveillance System survey, which includes questions on subjective cognitive decline, found that in the United States, 11% of Americans age 45 and older reported subjective cognitive decline, but 54% of those who reported it had not consulted a health care professional. 205 Individuals concerned about declines in memory and other cognitive abilities should consult a health care professional.…”

Section: Prevalence Of Subjective Cognitive Declinementioning

confidence: 99%

2020 Alzheimer's disease facts and figures

2020

Alzheimer's & Dementia

1,880

638

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This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the future challenges of meeting care demands for the growing number of people living with Alzheimer's dementia in the United States with a particular emphasis on primary care. By mid‐century, the number of Americans age 65 and older with Alzheimer's dementia may grow to 13.8 million. This represents a steep increase from the estimated 5.8 million Americans age 65 and older who have Alzheimer's dementia today. Official death certificates recorded 122,019 deaths from AD in 2018, the latest year for which data are available, making Alzheimer's the sixth leading cause of death in the United States and the fifth leading cause of death among Americans age 65 and older. Between 2000 and 2018, deaths resulting from stroke, HIV and heart disease decreased, whereas reported deaths from Alzheimer's increased 146.2%. In 2019, more than 16 million family members and other unpaid caregivers provided an estimated 18.6 billion hours of care to people with Alzheimer's or other dementias. This care is valued at nearly $244 billion, but its costs extend to family caregivers’ increased risk for emotional distress and negative mental and physical health outcomes. Average per‐person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2020 for health care, long‐term care and hospice services for people age 65 and older with dementia are estimated to be $305 billion. As the population of Americans living with Alzheimer's dementia increases, the burden of caring for that population also increases. These challenges are exacerbated by a shortage of dementia care specialists, which places an increasing burden on primary care physicians (PCPs) to provide care for people living with dementia. Many PCPs feel underprepared and inadequately trained to handle dementia care responsibilities effectively. This report includes recommendations for maximizing quality care in the face of the shortage of specialists and training challenges in primary care.

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“…For the definition of our SCD group, we followed the recently developed framework proposed by Jessen et al [35]. Future studies could investigate the predictive value of enriching information about this group by reporting longitudinal stability [101] or including genetic data or biomarker evidence, which is of particular importance as individuals with SCD are twice as likely to develop AD as older individuals without complaints [102].…”

Section: Disrupted Functional Coupling Of Prefrontal and Parietal Dmnmentioning

confidence: 99%

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

Dillen¹,

Jacobs

Kukolja

et al. 2017

JAD

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Abstract. Neurodegenerative brain changes can affect the functional connectivity strength between nodes of the default-mode network (DMN), which may underlie changes in cognitive performance. It remains unclear how the functional connectivity strength of DMN nodes differs from healthy to pathological aging and whether these changes are cognitively relevant. We used resting-state functional magnetic resonance imaging to investigate the functional connectivity strength across five DMN nodes in 25 healthy controls (HC), 28 subjective cognitive decline (SCD) participants, and 25 prodromal Alzheimer's disease (AD) patients. After identifying the ventral medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), retrosplenial cortex (RSC), inferior parietal lobule, and the hippocampus we investigated the functional strength between DMN nodes using temporal network modeling. Functional coupling of the vmPFC and PCC in prodromal AD patients was disrupted. This vmPFC-PCC coupling correlated positively with memory performance in prodromal AD. Furthermore, the hippocampus decoupled from posterior DMN nodes in SCD and prodromal AD patients. There was no coupling between the hippocampus and the anterior DMN. Additional mediation analyses indicated that the RSC enables communication between the hippocampus and DMN regions in HC but none of the other two groups. These results suggest an anterior-posterior disconnection and a hippocampal de-coupling from posterior DMN nodes with disease progression. Hippocampal de-coupling already occurring in SCD may provide valuable information for the development of a functional biomarker.

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Differential Risk of Incident Alzheimer’s Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline

Abstract: These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Cited by 73 publications

References 41 publications

Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia

Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia

2020 Alzheimer's disease facts and figures

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

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