Neuroplasticity and Immunology in Mild Cognitive Im-pairment and Alzheimer’s Disease


Cognitive decline in aging has previously been seen as an inevitable consequence of aging. However, recent results from research on neuroplasticity suggest that cognitive decline in aging can be prevented and may even be reversed through behavioral trainings based on principles of neuroplasticity. Thus, methods that allow for an early diagnosis of pathological aging and beginning dementia, in combination with secondary preventive trainings, are of high societal importance.

In this collaborative project, partners from the field of Neuropsychology, Analytical Chemistry and Clinical Neurology/Medicine work together to evaluate the validity of new biomarkers in blood serum and cerebrospinal fluid for the early diagnosis of beginning Alzheimer's disease. Another main focus of the project is the investigation of the relationship between biomarkers and neuroplastic changes in the brain by using functional brain imaging techniques. Finally, the efficacy of a neuroplasticity-based behavioral training to prevent cognitive decline in elderly persons with beginning Alzheimer's disease will be evaluated. Immunoanalytical methods, mass spectrometry and functional brain imaging techniques will be used to investigate functional changes in the brain in the course of the training.

  • Department of Chemistry
  • Department of Psychology
  • Zukunftskolleg
  Thurm, Franka (2012): Aging and dementia : Clinical relevance of early markers and late interventions

Aging and dementia : Clinical relevance of early markers and late interventions


The human life expectancy is steadily rising worldwide. Currently, the maximum life span is 122 years. This remarkably old age was reached by Jeanne Calment. She was born on 21 February 1875 in France and died on 4 August 1997. She became 122 years and 164 days old and was cognitively fit throughout. According to the Gerontology Research Group (, altogether 70 so-called supercentenarians (among those 65 women) aged 110-115 years exist at present (last updated on 4 April 2012). Supercentenarians seem to evade or at least postpone the negative influence of age-associated morbidity including as vascular diseases and diabetes (Schoenhofen et al., 2006). More than 80% of the over-90-year-olds live independently (Perls, 2002). What is their secret? A healthy lifestyle concerning diet, physical exercise and health behavior is associated with up to ten years longer life expectancies (Fraser & Shavlik, 2001). Genetics play a moderate role, having a 20-30% influence on survival (e.g., Herskind et al., 1996; Perls, 2002). Longevity (i.e., > 90 years of age) reoccurs more often in siblings who have at least one very old family member (e.g., Perls et al., 2007). However, exceptional longevity (i.e., > 110 years of age) is still very rare. It is further unclear how genetic and environmental factors contribute to healthy survival beyond the 11th decade (Leslie, 2008; Sebastiani et al., 2012).
In Germany, 200,000 older adults develop Alzheimer’s disease (AD) per year. After the diagnosis it takes approximately seven years until death. However, the pathological, neuronal changes already start decades before Alzheimer-associated memory and behavioral problems become obvious ( Hence, the main goals of aging and dementia research focus on the detection of possible biomarkers to allow early diagnosis of pathological cognitive decline and AD as well as on the development of efficient intervention approaches for patients already affected by dementia.
For this thesis, four studies have been carried out to investigate potential biomarker candidates for AD and a late intervention approach for dementia patients with comorbid physical restraints. Study 1 focused on the establishment of a new ELISA (enzyme-linked immunosorbent assay) method for the determination of physiological, naturally occurring beta-Amyloid autoantibody complexes (Aβ-IgG immune complexes) in serum of 47 healthy adults aged 18-89 years. Results showed no association of the Aβ-IgG immune complexes with age or cognitive test scores of the participants, indicating that healthy aging is not necessarily associated with an altered production of Aβ-autoantibodies or with a decreased Aβ cleaving in the periphery.

In study 2, this new ELISA method was also applied for the determination of Aβ-IgG immune complexes in serum and cerebrospinal fluid (CSF) of 58 Alzheimer patients compared to 54 non-demented control subjects. AD patients showed significantly higher levels of Aβ-IgG immune complexes in serum and CSF than controls. Sensitivity and specificity were not sufficient for the application as a self-standing biomarker of AD in clinical routine. However, Aβ-IgG immune complexes in serum, which can be obtained minimally invasive, could provide supplemental information for early diagnosis of AD and for therapy monitoring in the future.

Study 3 investigated the error-related negativity (ERN) and the correct-related negativity (CRN) by means of electroencephalography (EEG) in 14 older adults with mild cognitive impairment (MCI), 16 younger and 16 older adult control subjects. MCI refers to a gray zone between healthy and pathological aging or AD. Results showed a significant alteration in MCI patients compared to both control groups. In contrast, healthy older adult controls showed no difference compared to the younger adult control subjects. Event-related potentials (ERPs) could therefore provide additional information for early diagnosis of MCI and AD, although the biomarker criteria are not yet fulfilled.

Finally, study 4 investigated the efficiency of a multimodal physical training in a small sample of institutionalized and physically very frail nursing home residents with dementia. Cognitive performance of the training group stabilized and partially improved after ten weeks of training compared to control subjects who showed further cognitive deterioration. This result indicates that physical training is applicable and effective even in cases with progressing dementia and physical restraints.

Origin (projects)

Funding sources
Name Finanzierungstyp Kategorie Project no.
Heidelberger Akademie third-party funds research funding program 874/08
Further information
Period: 01.07.2007 – 30.06.2012