Summary: A combination of patient-reported subjective cognitive decline and measurable clinical markers—such as elevated beta-amyloid levels in cerebrospinal fluid—may improve early detection of Alzheimer’s disease.
Source: DZNE
Subjective memory complaints together with clearly abnormal levels of beta-amyloid in the cerebrospinal fluid strongly indicate a developing Alzheimer’s disease. This conclusion comes from a DZNE study involving nearly 1,000 older adults.
A team led by dementia researcher Frank Jessen reports these results in the journal Alzheimer’s & Dementia.
The findings may help refine approaches for earlier diagnosis and intervention in Alzheimer’s disease.
When people perceive a decline in memory or other cognitive abilities but standard objective tests do not detect impairment, clinicians describe this as “subjective cognitive decline” (SCD). This phenomenon has been the focus of research for several years.
“Affected individuals report cognitive problems that cause them real concern but are not measurable with current testing,” explains Prof. Frank Jessen, a DZNE scientist and director of the Department of Psychiatry at the University of Cologne. Research has shown that SCD is a risk factor for dementia, but it is not by itself a definitive predictor.
“Many people with SCD do not experience progressive cognitive decline. To estimate an individual’s risk more reliably, additional measures must be considered,” Jessen says. “Our study clarifies that when SCD occurs together with evidence of certain protein accumulations in the brain—specifically beta-amyloid—this combination is a strong sign of early Alzheimer’s disease.”
A nationwide study
These conclusions are drawn from the DELCODE study, a long-term, multicenter DZNE project conducted across ten study sites in Germany, involving several university hospitals. Within DELCODE, nearly 1,000 older men and women have undergone annual cognitive assessments for several years.
Participants were evaluated using established neuropsychological tests. Many also underwent cerebrospinal fluid (CSF) analysis to measure biomarkers and magnetic resonance imaging (MRI) to determine brain volume.
Jessen and colleagues analyzed longitudinal data sets for each participant covering up to five years. The mean age of participants was approximately 70. They were recruited through memory clinics at participating hospitals and via advertisements.
The cohort comprised over 400 individuals who had SCD at baseline, around 300 people with measurable cognitive impairments (ranging up to Alzheimer’s-related dementia), and more than 200 cognitively normal adults without SCD who served as a control group. Taken together, this makes DELCODE one of the most comprehensive SCD studies to date.
Biomarkers in the cerebrospinal fluid
A central focus of the study was the protein beta-amyloid, which accumulates in the brain during the course of Alzheimer’s disease.
Beta-amyloid accumulation in the brain can be inferred indirectly by measuring its concentration in cerebrospinal fluid: levels below a defined threshold are taken as evidence of beta-amyloid deposition in the brain, a status commonly described as “amyloid-positive.” In this cohort, 83 participants with SCD and 25 of the control participants were classified as amyloid-positive.
“Like SCD, beta-amyloid deposition is a risk factor for Alzheimer’s disease; neither marker alone is a definitive indicator. Our study shows that considering these markers together over time gives a much clearer picture of who is likely on an Alzheimer’s disease trajectory,” Jessen notes.
Development over time
Over the course of the study, some individuals from both the SCD and control groups progressed to measurable cognitive impairment. This progression was particularly pronounced among participants who were amyloid-positive and reported SCD at baseline.
In contrast, amyloid-positive individuals in the control group—who did not report SCD—showed, on average, considerably less cognitive decline. MRI analyses supported these differences.
The hippocampus, a paired brain structure crucial for memory, tended to be smaller in amyloid-positive participants with SCD than in amyloid-positive participants from the control group, suggesting greater hippocampal atrophy and loss of brain tissue in the SCD–A+ subgroup.
Stage 2 of Alzheimer’s disease
“Putting together all findings, including data from participants who already displayed measurable cognitive deficits at baseline, we interpret the combination of SCD and amyloid-positive status as a strong indicator of early-stage Alzheimer’s disease,” Jessen says.
“When Alzheimer’s is categorized into six stages, with stage 6 representing severe dementia, we consider the combination of SCD and amyloid-positivity to correspond to stage 2. This stage precedes the point at which objective cognitive deficits first become measurable and is often referred to as the preclinical phase before mild cognitive impairment.”
An approach for early detection
Currently, no fully effective cure exists for Alzheimer’s disease. Most experts agree that therapeutic interventions will be more effective the earlier they are initiated.
“By the time clear clinical symptoms are present, significant and often irreversible brain damage has typically occurred, limiting the potential for lasting treatment benefit,” Jessen explains.
“The key challenge is identifying apparently healthy individuals who nonetheless harbor Alzheimer’s pathology and are at high risk of future decline. We believe the combination of subjective cognitive decline and amyloid-positive CSF status is a promising criterion that warrants further investigation in future studies and could help target early interventions and monitoring.”
About this Alzheimer’s disease research news
Author: Press Office
Source: DZNE
Contact: Press Office – DZNE
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Original Research: Open access. “Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers” by Frank Jessen et al. Alzheimer’s & Dementia
Abstract
Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers
Introduction
It remains uncertain whether subjective cognitive decline (SCD) among help-seeking individuals reliably identifies the earliest symptomatic stage (stage 2) of the Alzheimer’s disease continuum.
Methods
Cross-sectional and longitudinal data were analyzed from the multicenter, memory clinic–based DELCODE study.
Results
The SCD group displayed slightly worse cognitive performance and more subtle functional and behavioral symptoms than the control group (CO). SCD–A+ cases (39.3% of all SCD participants) showed greater hippocampal atrophy, lower cognitive and functional scores, and more behavioral symptoms than CO–A+ participants. Amyloid concentration in CSF had a stronger effect on longitudinal cognitive decline in the SCD group than in the control group.
Discussion
Our data suggest that SCD helps identify stage 2 of the Alzheimer’s disease continuum and that stage 2, operationalized as SCD–A+, is associated with a subtle but broader impact of AD pathology in terms of neurodegeneration, symptoms, and clinical progression.