BACKGROUND Neurocognitive symptoms have a high prevalence in cancer patients, resulting in a significant impact on daily life and tolerance to therapy. It's estimated that about 30% of cancer patients present a cognitive impairment before treatment, about 75% present this cognitive impairment during the treatment, and about 35% continue to present cognitive difficulties in the following months/years.

There is growing evidence that cognitive symptoms have a biological mechanism linked to the activation of immunological cytokines that exert important effects on the brain functions. For example, interferon α is known to increase the levels of IL-1, IL-6 and TNF-α, and this increase is associated with memory deficits, executive function and mood alterations.

A neurotoxic action induced by cytokines has been demonstrated both in the early stages of the tumor and after chemotherapy.

Several imaging studies suggest that the cognitive impairment pattern in cancer patients, during the treatment and in remission, is related to structural and functional brain changes.

Longitudinal studies in women with breast cancer treated with chemoterapy have shown a reduction in the volume of cerebral gray matter, mainly in the bilateral frontal cortex and hippocampus. In parallel, diffusion tensor imaging studies have shown an alteration of the integrity of the frontal, parietal and occipital cerebral white matter, demyelination and axonal degeneration processes. Finally, functional magnetic resonance studies in cancer patients have shown alterations in the connectivity of the default mode network compared to control subjects.

Studies carried out to date, show a prevalent impairment of executive functions and working memory. Cognitive impairment has been studied mainly as a possible adverse effect in women treated with chemotherapy for breast cancer, while there are few studies in the literature on patients with haematological malignancies.

STUDY DESIGN The study is targeted to patients ages ≥ 70 years, whith haematological malignancy, who need to start a treatment within 3 months.

Once the eligibility criteria have been assessed, the hematologist proposes the enrollment in the study. Once the patient's informed consent has been acquired, a neurological examination is carried out, functional tests required by the protocol are administered. The patient begins, as per clinical practice, the treatment provided for his/her haematological malignancy. Test's evaluation is repeated at 6 months and 12 months after the enrollment. In conjunction with neurological tests, will be performed a venipuncture as per clinical practice, and a blood sample is taken to measure the cytokines involved in inflammatory processes. It is expected that a patient can perform up to a maximum of 3 blood samples for the biological study.

STATISTICAL ANALYSIS This is a non-pharmacological, prospective, uncontrolled, open-label single-center interventional pilot study, aimed to describ the progress of cognitive function under treatment for haematological disease.

Due to the pilot and exploratory nature of the study and the substantial absence of a specific literature relating to the elderly onco-haematological patient, it is not believed that the conditions exist to be able to formally define the size of the sample. The sample size is arbitrarily fixed at 60 patients. The observation time will be 12 months from enrollment.

Inclusion Criteria:

• Ages ≥ 70 years;
• Signed Informed Consent Form;
• Haematological malignancy diagnosis that requires whithin three months a treatment.

Exclusion Criteria:

• Inability (ex. severe visual and/or hearing impairments, lack of caregivers) to carry out the tests required by the study;
• Comorbidity or condition that, in the investigator's opinion, may compromise the safe execution of the tests.