Usually, the effects of cognitive decline are not noted before the age of 70 years, which involve the intellectual capacities, the attention, the processes of elaboration and the memory. The studies on the cognitive disturbances of the elderly are numerous, and document the progressive increase of cerebral deterioration with advancing age. However, only a few studies refer to the significance of the cognitive disturbances in the clinical conditions and autonomy of the long living subjects. For this reason, we studied the cerebral deterioration of an adequate number of centenarians in correlation with their clinical conditions and autonomy. Our centenarian sample derived from the Italian multi-center study on centenarians (IMUSCE), which was an epidemiological study which identified 1173 centenarians (202 males, 971 females) in the age range of 100-109 years. From this sample, we analyzed 346 subjects as far as the cognitive functions and the degree of autonomy by using the psychometric tests of the mini-mental state examination (MMSE) and the instrumental activities of daily living (IADL) for the functional evaluations. In addition, we evaluated the clinical conditions of the subjects dividing them in three groups: Group A (those in good clinical conditions), Group B (those in discrete clinical conditions), and Group C (those in deteriorated clinical conditions). These analyses revealed that 187 (54.1%) of the 346 examined centenarians have shown an MMSE score in the normal range (score ratio from 1.0 to 0.63). The cognitive disorders are present in the centenarians in a clearly higher frequency (13.1%), than found in the common elderly (5.1%). The severe cognitive disorders do not allow a total autonomy or even a slight dependency. Only six subjects (1.7%) of the total sample were totally independent. These subjects had no cognitive disorders, and were in good clinical conditions. The results show that having an MMSE score in the normal range, and being in good clinical conditions are necessary but not sufficient prerequisites for a total autonomy in the IADL scores.