Combination of ‘feelings’ and measurements suggest early-stage Alzheimer’s

Summary: A combination of patient-reported subjective cognitive impairment and measurable clinical signs, such as accumulation of amyloid beta in the cerebrospinal fluid, may aid in the early diagnosis of Alzheimer’s disease.

Source: DZNE

Subjective memory impairments coupled with marked levels of beta-amyloid proteins in the cerebrospinal fluid are a strong indicator of developing Alzheimer’s disease. This is the conclusion of a DZNE study of approximately 1,000 older adults.

A team led by dementia researcher Frank Jessen reports on these findings in the journal Alzheimer’s & Dementia

The research results may contribute to the early detection and treatment of Alzheimer’s disease.

When people feel that their memory or other mental abilities are declining, but objective tests reveal no deterioration, it is referred to in medicine as “subjective cognitive impairment,” or SCD for short. The phenomenon has been the subject of research for years.

“The affected individuals report cognitive problems that are of serious concern to them, but which are not measurable with current techniques,” explains Prof. Frank Jessen, a DZNE scientist and director of the Department of Psychiatry at the University of Cologne. It has since been shown that SCZ is a risk factor, but not a conclusive warning sign of impending dementia.

“In many people with SCD, there is no progressive loss of cognitive performance. In order to estimate individual risk more accurately, other factors need to be taken into account,” says the researcher. “We have now been able to specify those. There are also indications that certain proteins accumulate in the brain, which together is a strong sign of developing Alzheimer’s disease.”

A national study

This assessment is based on a long-term DZNE study called DELCODE, which includes ten study centers across Germany and involves several teaching hospitals. In this context, the cognitive performance of nearly 1,000 older women and men has been registered annually for several years now.

This is done through established neuropsychological testing procedures. In addition, the cerebrospinal fluid of many study participants is analyzed and the brain volume determined by means of magnetic resonance imaging (MRI).

Jessen and his colleagues now evaluated measurement series of the individual subjects, with each data set covering a period of up to five years. The mean age of the study participants was approximately 70 years and they were originally recruited through memory clinics in the participating teaching hospitals and through newspaper advertisements.

The cohort included more than 400 people with SCD at baseline and about 300 people with measurable cognitive impairment, up to symptoms of dementia due to Alzheimer’s disease.

In addition, the cohort consisted of more than 200 adults whose cognitive performance was within the normal range and who did not show SCD at baseline: these “healthy” individuals served as a control group. Overall, this is one of the most comprehensive studies of SCD to date.

Cerebrospinal fluid biomarkers

The protein beta-amyloid, which accumulates in the brain during Alzheimer’s disease, played an important role in the studies.

Accumulation in the brain can be assessed indirectly – based on the level of the protein in the cerebrospinal fluid: if the reading exceeds a threshold, it is considered evidence that beta-amyloid is concentrating in the brain. These individuals are then considered “amyloid positive”. 83 study participants with SCD and 25 volunteers from the control group had this status.

“Deposition of beta-amyloid, such as SCD, is a risk factor for Alzheimer’s disease. By itself, however, neither phenomenon is a clear indicator of disease. But the picture becomes sharper, as our study shows, when these phenomena are considered together and over a longer period of time,” says Jessen.

Development over time

During the study period, some subjects from the SCD group and also some from the control group developed measurable cognitive deficits. This was especially evident in amyloid-positive subjects with SCD at baseline.

In comparison, cognitive decline was, on average, much lower in amyloid-positive control subjects. Brain MRI data also showed differences:

The “hippocampus”, a brain region divided into both hemispheres and considered the “control center” of memory, was tended to be smaller in amyloid-positive subjects with SCD than in amyloid-positive subjects of the control group: an indication of atrophy, i.e. loss of brain mass.

Stage 2 of Alzheimer’s disease

“When you add up all the findings, including data from the subjects who already had measurable cognitive impairment at baseline, we see the combination of SCD and amyloid-positive status as a strong indicator of early-stage Alzheimer’s disease,” says Jesse.

The protein beta-amyloid, which accumulates in the brain during Alzheimer’s disease, played an important role in the studies. Image is in the public domain

“If you classify Alzheimer’s disease into six stages according to common practice, where stage 6 represents severe dementia, then in our opinion the combination of SCD and amyloid positive status corresponds to stage 2. This occurs before the stage where measurable symptoms appear for the first time. and which is also referred to as mild cognitive impairment.”

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An approach to early detection

To date, there is no effective treatment for Alzheimer’s disease. However, it is generally believed that therapy should begin as early as possible.

“If there are measurable clinical symptoms, then the brain is already badly damaged. From a contemporary perspective, treatment then has little chance of lasting success,” says Jessen.

“The question is therefore how to identify apparently healthy individuals who actually have Alzheimer’s disease and are at high risk of developing dementia. I consider the combination of SCZ and amyloid-positive status to be a promising criterion to be further explored and tested in future studies.”

About this research news on Alzheimer’s disease

Writer: press office
Source: DZNE
Contact: Press agency – DZNE
Image: The image is in the public domain

Original research: Open access.
“Subjective cognitive decline and stage 2 Alzheimer’s disease in patients from memory centers” by Frank Jessen et al. Alzheimer’s & Dementia


Subjective cognitive decline and stage 2 Alzheimer’s disease in patients from memory centers


It is uncertain whether subjective cognitive decline (SCD) in individuals seeking medical attention serves to identify the initial symptomatic stage 2 of the Alzheimer’s disease (AD) continuum.


Cross-sectional and longitudinal data from the multicenter, memory clinic-based DELCODE study.


The SCD group showed slightly worse cognition and more subtle functional and behavioral symptoms than the control group (CO). SCD-A+ cases (39.3% of all SCD) showed more hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO-A+. CSF amyloid concentration had a greater effect on longitudinal cognitive decline in SCD than in the CO group.


Our data suggest that SCD serves to identify stage 2 of the AD continuum and that stage 2, operationalized as SCD-A+, is associated with subtle, yet extensive impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression.

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