Aging and cognitive Performance

Do cognitive and psychosocial factors
lead contribute to neurobiological
changes of during aging?

Head

Prof. Dr. med. Emrah Düzel

Staff

Collaborations

National and international Collaborations are an important part of the age-research in Magdeburg. The important collaborations are listed below.

1) With the University College London (Prof. Neil Burgess): A behavioural paradigm of topographic memory developed by Prof. Burgess was used in our aging study

2) With the Max-Planck-Institute for Human Development in Berlin and the Karolinska Institute in Stockholm (Prof. Ulman Lindenberger and Prof. Lars Bäckmann): A joint project on prefrontal plasticity and cognitive training.

3) With the University of California Davis (Prof. Yonelinas): Structural and functional age-related brain-characteristics leading to a decline of semantic and episodic encoding.

The Magdeburg Aging study

Memory loss and cognitive slowing tend to decline across the adult lifespan. Compared to young adults, More than 40 percent of the healthy aged adults show a decreased ability to remember personal events and episodes. Adults age 65 years and older are the fastest growing segment of our population. This demographic change, which is especially prevalent within the working population, is compelling researchers public health agencies to find ways to improve the mental and cognitive health of older adults. Because of its pervasive social impact, numerous investigations have been initiated worldwide to understand causes and consequences of age related changes in cognitive function, and the development of strategies to maintain or enhance cognitive function in later life has become an important public health goal.

Recent structural and functional imaging studies e.g. magnetic resonance imaging (MRI) show that the memory and cognitive in the elderly are associated with structural and functional changes in the aging brain. It has been hypothesized that psychosocial factors - such as job-related tensions and cognitive stress, individual behavior patterns for coping and recovering from stress, and differences in the availability of social and organizational resources - can affect the changes in cognitive performance that occur over the lifespan. Stress research studies, for instance, have provided strong evidence that special psychosocial and salutogentic factors can affect age related neurobiological changes. Although the study of the aging brain is becoming a popular field of inquiry, only a few studies have attempted to combine the psychosocial and neurobiological approaches to aging to comprehensively investigate the links between those factors.

The Magdeburg Aging Study is a multidisciplinary study being carried out by the Clinical Research Group “Cognitive Control of Memory Functions” (). For additional details see subprojects 1 and 3. The present subject pool is comprised of a population of 85 healthy older people, aged 54-85 years, with 25 young adults serving as a control group. The study is intended to investigate normal, healthy aging, so individuals with metabolic diseases like diabetes mellitus, untreated hypertension, neurological or psychiatric conditions have been excluded. All subjects have normal or corrected to normal visual acuity are right-handed by self-report, and report no serious hearing problems.

A comprehensive dataset has been acquired from each participant. In addition to neuropsychological variables, standardized psychosocial and salotogenetic parameters were obtained Specified structural and functional MR diagnostics and neuropsychological tests were applied to gather structural and functional data about age-related cognitive performance and neurobiological changes. Additionally, blood samples were taken from each participant to characterize specific genetic polymorphisms. This multidisciplinary dataset thus combines neurobiological, psychosocial, salutogenetic, cognitive and genetic data on the aging brain.

The relatively large number of elderly participants has enabled us to subdivide the study sample into groups based on specific structural parameters (e.g. high/low Grey Matter distinctions, MT ratio, Anisotrophy, Polymorphisms). The following figure provides a structural overview of the Magdeburg Aging Study and the data being acquired.

Fig. 1:

Structural MTR

A neuro-optimized 1.5-T GE Signa Horizon LX scanner with the standard quadrature head coil (GE,Milwaukee,WI) and a 3T Siemens Magnetom Trio with a 8-channel headcoil were used for MR scanning at the Department of Neurology in Magdeburg. An anatomical whole-brain image was acquired from each participant using the different scans listed below:

• High resolution anatomical scans.

• Protondensity scans

• Diffusion Tensor Imaging.

• Magnetization Transfer Imaging.

• Spektroskopy.

Neuropsychological assessment of cognitive sub-functions

All participants underwent neuropsychological assessment to test their attention, cognitive processing speed, concentration, figural and verbal memory. Specific tests are listed below.

• Mini Mental Status Test (MMST),

• Geriatric Depression Scale (GDS),

• Multiple choice vocabulary-intelligence Test (Mehrfachwahl- Wortschatz-Intelligenztest, MWT-B),

• California Verbal Learning Test (CVLT),

• “Diagnosticum für Cerebralschädigung” (DCS), a non Verbal Learning Test,

• Digit Span assessment [Harting, 2000 #3327],

• The Controlled Oral Word Association Test (COWAT), a word fluency assessment (adapted German version).

• Trail Making Test part A and B ,

• D2 test of attention

Fig. 2:

Psychosocial assessment

Animal studies and human investigations have shown that the age-related declines in function are associated with environmental and personal lifestyle factors. Specific individual traits, social interactions and physical exercise are just some of the factors which influence age-related memory processing. An active physical and mental life can prevent age-related cognitive decline, as can objective lifestyle-factors and resources, such as an interesting and varied job history, and ongoing cognitive challenges. Furthermore, individual traits, like stress-coping abilities, , and distinctive sense of coherence, are related to the preservation and development of various physical and psychological functions over an individuals lifespan. The ability to cope with changes and losses during aging seems to be an important cognitive resource. Identifying the mechanism responsible for the structural and functional decline in old-age, and determining the factors that are correlated with preserved cognition, are important research goals of our aging study.

The following psychosocial parameters were assessed.

• Job-history (Qualification, learning and qualifying options, participation, social support within the work environment)

• Inventory of life events and stresses (LEBI) (critical life events, psychosocial strains, life goals)

• Sense of coherence questionnaire (SOC 78)

• Stress coping questionnaire (SV 70) Freiburger list of medical conditions

• Review of the individual's state of health

• Questionnaire about the person's economic state and health related behaviours

Fig. 3:

Additionally weight, height, blood-pressure, pulse, ultrasound of the extra and intracranial arteries, a finger tapping test and blood samples were acquired from each participant.

Functional studies

Functional imaging studies measured neural activation with a high degree of anatomical or temporal precision. They can be used to probe the activity of brain structures believed to be necessary for instance for the encoding or the retrieval of memories. They are therefore, an important complement to our structural studies. We use Magnetoencephalography and functional Magnetic Resonance Tomography to measure brain activity. We are particularly interested how brain regions known to release important memory related neurotransmitters such as dopamine and acetylcholine (midbrain and basal forebrain) and their target regions (hippocampus, prefrontal cortex). Since we obtain these functional parameters from the same adults who have also contributed to the structural data set, we are able to establish structure-function relationships. To give an example, we could recently show that the structural integrity of dopaminergic midbrain regions affects the how much the hippocampus is activated by novelty (Bunzeck et al., 2007).

Ausgewählte Publikationen/References

Szentkuti, A, Guderian, S., Schiltz, K., Kaufmann, J., Münte, T.F., Heinze, H.J., Düzel, E., (2004). Quantitative MR analyses of the hippocampus: Unspecific metabolic changes in aging. J Neurology. 251, 1345-1353.

Schiltz, K., A. Szentkuti, et al. (2006). Relationship between hippocampal structure and memory function in elderly humans. J Cogn Neurosci 18(6): 990-1003.

Bunzeck, N., Schütze, H., Stallforth, S., Kaufmann, J., Duzel, S., Heinze, H.J., Duzel, E.(accepted pending revision). Mesolimbic novelty processing in elderly. Cerebral Cortex.

Bunzeck, N. and E. Duzel (2006). Absolute stimulus-novelty is coded by the human substantia nigra/VTA. Neuron 3: 369-79.

Schott, B.H., Niehaus, L., Wittmann, B.C., Schütze, H., Seidenbecher, C.I., Heinze, H.J., Düzel, E. Aging and early-stage Parkinson’s disease affect separable neural mechanisms of mesolimbic reward processing. Submitted.

Duzel, S., Stallforth, S., Schütze, H., Kaufmann, J., Heinze, H.J., Duzel, E. A relatively specific effect of substantia nigra integrity on verbal memory in healthy aging. In preparation.