Correlation of frontal atrophy and CSF tau levels with neuropsychiatric symptoms in patients with cognitive impairment: a memory clinic experience

Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful 21 condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and 22 the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) 23 tau and brain atrophy. 24 Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s 25 disease; Lewy-body disease, LBD; frontotemporal dementia; vascular dementia) underwent a 26 complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed 27 with MTA, PA and GCA-F scales. BPSD were rated using Neuropsychiatric Inventory (NPI), and 28 BPSD clusters were defined according to the European Alzheimer Disease Consortium. 29 Results: Delusions, hallucinations and psychosis cluster were differently distributed among the 30 diagnostic groups (p<0.05, p<0.001, and p<0.05), with LBD patients showing higher scores for 31 hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In 32 primary dementias, we found a negative trend between NPI total score and tau levels (p=0.08), while 33 a positive relationship was observed in MCI (p=0.60). Higher GCA-F scores were associated to 34 delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: 35 p<0.05). GCA-F scores were positively correlated with delusions and psychosis cluster (right: 36 p<0.05), and agitation/aggression (left: p<0.05). Conversely, nighttime disturbances were positively 37 correlated with both GCA-F and MTA scores (left: p<0.01; right: p<0.05). 38 Conclusion: Our results suggest that psychotic symptoms are significantly more represented in LBD 39 patients and that CSF tau and frontal atrophy could be useful indicators of the occurrence and 40 severity of BPSD in clinical practice.