Demographic forecasts predict a rapid growth of the aged population in western societies. With regard to this demographic development an important goal in cognitive neuroscience research is to identify modifiable factors that help maintain cognitive functioning in old age. Among these, lifestyle and health related factors have become important pillars of current research on effective mechanisms for warding off structural and functional decline in the aging brain. Age-related decline in learning and memory, often termed as age-associated memory impairment (AAMI), is a well-documented finding in healthy old adults but the neurobiological underpinnings of this decline are still under debate. A consistent pattern of AAMI is a decrement in episodic memory apparent in impaired free recall and recollection. Evidence from lesion studies in humans and animals indicate that episodic memory is critically dependent on the integrity of the medial temporal lobes (MTL) and the prefrontal cortex. However, it has also been pointed out that AAMI is also a result of age-related dysfunction in the neuromodulation of the areas mentioned (dopaminergic and cholinergic neuromodulation). The focus of this study is to investigate the influence that age-related structural changes within the regions of origin of dopaminergic and cholinergic neuromodulation exert on learning and memory in aging and how health and lifestyle related factors (eg. body-mass-index (BMI) years of education, subjective mental health, sense of coherence (SOC) and coping might influence this relationship. A cross-sectional-study with 86 healthy older adults (age-range: 65-84 years) and 24 young adults (age-range: 18-30 years) was carried out to investigate these relationships. We observed a robust positive correlation between the structural integrity of the SN/VTA (the main origin of dopaminergic projections) and verbal learning and memory performance among older adults. We found that BMI had an impact on the SN/VTA integrity: older people with high BMI showed a reduced SN/VTA integrity compared to older people with a lower BMI. Basal forebrain integrity, main origin of cholinergic neurotransmission showed a significant relationship not only with learning and memory but also with working memory span. In contrast, lifestyle factors such as job prestige, years of education, positive coping, sense of coherence showed a weak impact on cognitive variables. In a voxel-based morphometry study we investigated the relationship between the sense of coherence (SOC) and structural changes in gray matter. The SOC is a subjective assessment of the ability of future oriented planning and prediction and to learn from prediction-errors. Sub-categories of this measure showed a robust correlation with gray matter density of the posterior cingulum (PCC). This finding has implications for developing early markers of Mild Cognitive Impairment (MCI) because where the PCC is one of the regions affected in early stages. Also, the PCC is implicated in episodic and prospective memory performance. The findings of this study will be discussed within a model which combines the taking into account the role of dopamine in novelty-processing as well as in explorative behaviours. On the basis of these findings it is possible to design new screening methods, which capture specific relationships between psychosocial factors and brain structures, like SN/VTA and PCC to better predict MCI. A long-term goal is to develop new lifestyle and health based strategies for prevention.