Alzheimer's diseas; white matter changes; leukoaraiosis; behavioral and psychological symptoms of dementia Objective: The frontal lobe may be involved in circuits associated with depression, apathy, aggression, and other psychiatric symptoms. Although white matter changes (WMC) are related to the severity of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), it is unclear which part of the WMC may play the most important role in BPSD. This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients. Methods: Among patients diagnosed with Alzheimer's disease between 2009 and 2014, 387 patients were retrospectively reviewed after those with pre-existing organic brain syndrome, psychiatric diseases, or toxic-metabolic encephalopathy were excluded. Patients' demographic and laboratory data, WMC measured with brain computed tomography and scored using the age-related white matter changes (ARWMC) scale, and neuropsychological tests, including the cognitive abilities screening instrument (CASI), the Mini-Mental State Examination (MMSE), the clinical dementia rating scale with sum-box (CDR-SB), and the neuropsychiatric inventory (NPI) were analyzed. Results: There was no significant difference in the NPI between patients with and without a history of stroke, hypertension, and diabetes. No significant difference in the NPI was identified between different sexes or different Apolipoprotein E (APOE) alleles. The NPI score was significantly correlated with the duration of education (r = -0.4515, P = 0.0172), CASI (r = -0.2915, P < 0.0001), MMSE (r = -0.8476, P < 0.0001), and CDR-SB (r = 2.2839, P < 0.0001). WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC (P = 0.0255). After adjusting for age, duration of education, and CASI, WMC in the right frontal lobe remained significantly associated with the NPI score (β = 3.8934, P = 0.042). Conclusions: WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis. Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.

KEYWORDSAlzheimer's diseas; white matter changes; leukoaraiosis; behavioral and psychological symptoms of dementia Objective:The frontal lobe may be involved in circuits associated with depression, apathy, aggression, and other psychiatric symptoms. Although white matter changes (WMC) are related to the severity of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), it is unclear which part of the WMC may play the most important role in BPSD. This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients. Methods: Among patients diagnosed with Alzheimer's disease between 2009 and 2014, 387 patients were retrospectively reviewed after those with pre-existing organic brain syndrome, psychiatric diseases, or toxic-metabolic encephalopathy were excluded. Patients' demographic and laboratory data, WMC measured with brain computed tomography and scored using the age-related white matter changes (ARWMC) scale, and neuropsychological tests, including the cognitive abilities screening instrument (CASI), the Mini-Mental State Examination (MMSE), the clinical dementia rating scale with sum-box (CDR-SB), and the neuropsychiatric inventory (NPI) were analyzed. Results: There was no significant difference in the NPI between patients with and without a history of stroke, hypertension, and diabetes. No significant difference in the NPI was identified between different sexes or different Apolipoprotein E (APOE) alleles. The NPI score was significantly correlated with the duration of education (r = -0.4515, P = 0.0172), CASI (r = -0.2915, P < 0.0001), MMSE (r = -0.8476, P < 0.0001), and CDR-SB (r = 2.2839, P < 0.0001). WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC (P = 0.0255). After adjusting for age, duration of education, and CASI, WMC in the right frontal lobe remained significantly associated with the NPI score (β = 3.8934, P = 0.042). Conclusions: WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis. Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.Citation Lin TC, Lin YH, Kao LL, Kao YH, Yang YH, Chou PS, Wu MN. An association between the location of white matter changes and the behavioral and psychological symptoms of dementia in Alzheimer's disease patients.