In this study, we have shown that the CRN patients who have received conformal radiation for NPC generally have manifestations in cognitive impairment and neuropsychiatric symptoms, and also found some typical characteristics that have not been reported previously.

We found that the CRN patients had significant change of cognitive function, mainly reflects in short term memory, delayed recall, language, attention, orientation, visuospatial and executive function. The results of our study are similar to those of Cheung [17, 18] and Hsiao [19] despite methodological differences. In these studies, RT had deleterious effects on cognitive function in NPC patients. For example, Cheung examined a group of NPC patients who had completed their radiotherapy previously, and found memory, language, motor ability, as well as executive functions were significantly impaired for those patients who developed temporal lobe necrosis after RT. Lesion volume was correlated significantly with the severity of cognitive deficits. Hsiao found that the cognitive functioning scores had significantly declined in the domains of short-term memory, language abilities, and list-generating fluency to patients at least 1year after completion of RT.

We also found a relatively high rate of general intelligence impairment among CRN patients, with 22.5% by the MMSE and 75% by the MoCA so affected. This result was inconsistent with Cheung`s study of remaining relatively intact general intelligence by the MMSE in CRN patients [18]. It is possibly related to a longer post-RT interval of mean 4.3years and bigger total RT dosage of mean 70.7 Gy in our cohort, compared with about 1 year and 58.4 Gy in the former. It has been confirmed that post-RT interval and total RT dosage are correlated with more severe CRN as well as cognitive defect respectively [20].

Compared to the MMSE, the MoCA provided more information in identification of cognitive impairment in a cohort of CRN patients, and cost only about 8 minutes to complete. It can be explained by the inclusion of subtests that measure more demanding assessment of executive function, visuospatial function, new learning, attention, and information processing speed. This is one of the few studies to assess the MoCA in NPC survivors with CRN. Because the MoCA was so well tolerated and disagreed with the MMSE in such a significant proportion of subjects, we believe that the MoCA is a more sensitive CRN-related cognitive screen suitable for clinical practice [21]. However, this study is limited by the lack of gold standard neuropsychological assessment, and a validation study further testing this preliminary hypothesis is warranted.

Another notable finding here is that CRN subjects have relatively more neuropsychiatric symptoms than those of their cerebral normal counterparts. The most frequent symptoms among subjects with CRN are irritability (87.5%), anxiety (72.5%) and depression (62.5%), with about 1 in 3 displaying agitation and apathy. Irritability, anxiety, depression, agitation, apathy and night-time behavior disturbances are significantly more frequent among subjects with CRN than those with normal MR image. Only subjects with CRN had psychotic symptoms including hallucinations and delusions.

The association between neuropsychiatric impairment and CRN has been recognized for some time, although lack of exact quantitative investigation. Nishimura reported clinical findings such as mental deterioration and motor abnormality in 12 NPC survivors with CRN [22]. Armstrong reported depression appears to increase years after RT, possibly first peaking somewhere between 4 and 6 years posttreatment [23]. Recently Tang examined a group of CRN patients with Self-Rating Anxiety Scale and Self-Rating Depression Scale, and found the patients with CRN got higher scores in both scales [24]. This result was consistent with our study of negative emotions in CRN patients.

The temporal lobes that easily involved in CRN are responsible for cognitive, emotional and psychological function. Radiation-induced damage to progenitor populations responsible for maintenance of white matter integrity and adult hippocampal neurogenesis has been suggested to play a major role in the neurocognitive impairment many cancer survivors experience [25]. The behavioral and psychological manifestations may, in part, be related to cerebral organic pathological changes (e.g., temporal lobe, limbic system, hippocampus) [26–28], and also social psychological attack (including RT adverse reaction, tumor deterioration) as well as cognitive dysfunction [29]. Post-RT patients, especially CRN victims, exhibit characteristic irritability. Though the specific cause is yet to be verified, attention should be paid to this syndrome in the long term survivors to improve their quality of life.

CRN patients who have received conformal radiation for NPC generally manifest cognitive neuropsychiatric symptoms with typical characteristics. However the study was limited by the relatively small sample size, and the lack of statistical differences found between groups (i.e. abstraction, delusion, hallucination, and aberrant motor activity) may not be a function of lack of differences, so that the results should be confirmed in some larger sample size and better match studies. Meanwhile, MoCA may be a feasible instrument for routine cognitive screening, but the sensitivity and specialty are not yet confirmed due to lack of gold standard in the study.