summary: A combination of patient self-reported cognitive impairment and measurable clinical symptoms, such as amyloid-beta buildup in cerebrospinal fluid, may aid in the early diagnosis of Alzheimer’s disease.
Subjective memory disturbances along with conspicuous levels of beta-amyloid proteins in the cerebrospinal fluid are a strong predictor of Alzheimer’s disease. This is the conclusion of the DZNE study of nearly 1,000 older adults.
A team led by dementia researcher Frank Jessen reported these findings in the journal Alzheimer’s disease and dementia.
The study findings could contribute to the early detection and treatment of Alzheimer’s disease.
When people feel that their memory or other mental abilities are deteriorating, but objective tests do not reveal any deterioration, this is referred to in medicine as “self-perceived impairment”, or coccomycosis for short. This phenomenon has been the subject of research for several years.
“Individuals affected have reported cognitive problems that cause them serious anxiety, but which cannot be measured with current techniques,” explains Professor Frank Jessen, DZNE scientist and director of the Department of Psychiatry at the University of Cologne. It is now clear that sickle cell disease is a risk factor, but it is not a definitive warning sign of upcoming dementia.
“In many individuals with sickle cell anemia, there is no progressive loss of cognitive performance. To assess individual risk more accurately, other factors must be taken into account,” says the researcher. “We have now been able to identify these. If, in addition to sickle cell disease, there is evidence of a build-up of certain proteins in the brain, bringing them together is a strong marker of Alzheimer’s disease.”
This assessment is based on a long-term DZNE study called DELCODE, which includes ten study centers across Germany and includes several university hospitals. Within this framework, the cognitive performance of approximately 1,000 elderly women and men annually has been recorded for several years.
This is done by established neuropsychological testing procedures. In addition, the cerebrospinal fluid of several study participants is analyzed and brain volume determined by magnetic resonance imaging (MRI).
Jessen and colleagues have now evaluated the measurement series of individuals, each data set covering a period of up to five years. The average age of the study participants was about 70 years old, and they were originally recruited through memory clinics at participating university hospitals and through advertisements in newspapers.
The group included more than 400 people with sickle cell anemia at baseline and about 300 individuals with measurable cognitive impairments – even symptoms of dementia due to Alzheimer’s disease.
In addition, the group included more than 200 adults whose cognitive functioning was within the normal range and who did not show sickle cell disease at baseline: these “healthy” subjects served as a control group. Overall, this represents one of the most comprehensive studies to date on social psychoanalysis.
Biomarkers of cerebrospinal fluid
The protein beta-amyloid, which accumulates in the brain during Alzheimer’s disease, has played an important role in the investigations.
Accumulation in the brain can be assessed indirectly – on the basis of the level of protein in the cerebrospinal fluid: if the reading exceeds the threshold value, this is considered evidence that beta-amyloid is concentrated in the brain. These individuals are then considered ‘amyloid positive’. 83 study participants with sickle cell disease and 25 volunteers from the control group had the condition.
“Beta-amyloid deposition, like sickle cell disease, is a risk factor for Alzheimer’s disease. However, neither phenomenon is a clear predictor of disease. But the picture is sharper, as evidenced by our study, when these phenomena are considered together and over a period of time. Longer lead times, says Jason.
Evolution over time
During the study period, some people from the SCD group and some from the control group developed measurable cognitive deficits. This was particularly evident in amyloid-positive subjects with sickle cell anemia at baseline.
In comparison, cognitive decline was significantly lower on average in amyloid-positive individuals than in the control group. Brain MRI data also showed differences:
The “hippocampus”, an area of the brain divided into two cerebral hemispheres and considered the “control center” of memory, tends to be smaller in people with amyloidosis with SCD than in individuals in the control group, and is an indication of atrophy, i.e. loss of brain block.
The second stage of Alzheimer’s disease
“When you combine all the results, including data from those people who already have measurable cognitive deficits at baseline, we see a combination of SCD and positive amyloid status as a strong predictor of early-stage Alzheimer’s,” Jessen says.
“If you classify Alzheimer’s into six stages according to common practice, with stage 6 representing severe dementia, then, in our opinion, the combination of SCD and amyloid-positive status corresponds to stage 2. This occurs before the stage in which measurable symptoms first appear that Also referred to as mild cognitive impairment.”
approach to early detection
To date, there is no effective treatment for Alzheimer’s disease. However, it is generally believed that treatment should begin as soon as possible.
“If there are measurable clinical symptoms, it means that the brain has already been significantly damaged. From today’s perspective, then treatment has little chance of lasting success,” says Jessen.
Thus, the question is how to identify apparently healthy individuals who already have Alzheimer’s disease and are very likely to develop dementia. I consider the combination of sickle cell disease and amyloid positivity status to be a promising criterion that should be further investigated and tested in future studies.”
About this research on Alzheimer’s disease news
original search: open access.
“Subjective cognitive decline and stage II Alzheimer’s disease in memory center patientsWritten by Frank Jessen et al. Alzheimer’s disease and dementia
Subjective cognitive decline and stage II Alzheimer’s disease in memory center patients
It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves to identify the initial symptomatic stage 2 of Alzheimer’s disease (AD).
Cross-sectional and longitudinal data from the memory clinic-based multicenter DELCODE study.
The sickle cell disease group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). Cases of SCD-A+ (39.3% of all patients with sickle cell disease) showed greater hippocampal atrophy, lower cognitive and functional symptoms, and more behavioral symptoms than CO-A+. The concentration of amyloid in cerebrospinal fluid had a greater effect on longitudinal cognitive decline in SCD than the CO group.
Our data indicate that SCD serves to define stage 2 of AD continuity and that stage 2, which is triggered as SCD-A+, is associated with a subtle but extended impact of Alzheimer’s pathology in terms of neurodegeneration, symptoms and clinical progression.