**9. Conclusions**

iNPH remains a complex and underestimated disease. As far cognitive impairment, this has commonly been described as fronto-subcortical dementia, but on the basis of the data of the literature we can assume that this term is reductive as it does not fully describe the different clinical pictures observed with an involvement of many other cognitive domains. Even after many years we still agree with the remarks of Iddon et al. in 1999 [50] "There may not be one single form of dementia syndrome in NPH but rather, there are varying degrees of cognitive change pre-shunt, according to the amount of permanent brain damage that has already taken place, compounded by comorbidity factors such as hypertensive cerebral small vessel disease". Undoubtedly, many other variables differently modulate and interfere with the disease expression. Moreover, an overlap with other neurodegenerative diseases can exist; this may be a complex and prognostic issue and could partly explain both the progression of cognitive decline and the absence of amelioration after successful CSF shunt procedures. With regard to the possible overlap with AD in particular, the weight of Alzheimer pathology in iNPH patients is not clear; studies investigating possible biological markers in fact have failed to obtain conclusive results.

The great variability of clinical pictures in iNPH has to be interpreted also taking into account the role of the "cognitive reserve" phenomenon [100]; even partially, this aspect can also contribute to the differences of the response to shunt surgery.

Clinical and neuroimaging data are crucial for the diagnosis and the literature has provided guidelines and precise neuroradiological diagnostic criteria. However, there is no general agreement about the neuropsychological measures to employ in assessing the condition, as the studies reported in the literature used different cognitive tests; this aspect is obviously relevant to the post-shunt follow-up, too. The neuropsychological assessment has to include sensitive and exhaustive measures investigating the different cognitive domains; also patients' quality of life and caregivers' point of view have to be investigated in particular after shunt surgery in order to obtain a more global and sensitive evaluation.

Another important issue is represented by the difficulty to establish with precision the different stages in the disease. The studies reported in the literature have been conducted in patients with different disease durations and therefore with different degrees of disease severity; this makes it difficult to compare the different results and obviously the results after shunt placement may well be negatively affected in patients with more severe or longer lasting disease. In particular as regards the shunt procedure, reliable indices predictive of a good response to surgery are still lacking; in the studies analyzed different outcome measures were employed in different follow-up periods.

We can conclude that there is a need for further studies with a better standardization; longer follow-ups and closer interaction among the different professionals involved are also requested.
