Comparison Of Neuropsychological Impairment Between Patients With Early-onset And Late-onset Alzheimer’s Disease And Difference Analysis On Texture Features Of Aβ-PET Images

Part One Comparison of neuropsychological impairment between patients with early-onset and late-onset Alzheimer’s diseaseObjective: To compare the neuropsychological impairment between patients with early-onset and late-onset Alzheimer’s disease(AD).Methods: From October 2018 to February 2021,315 patients with cognitive impairment who visited the memory clinic of the Neurology Department of our hospital were tested with Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(Mo CA),Clock Drawing Test(CDT),Boston Naming Test(BNT),Activity of Daily Living Scale(ADL),Neuropsychiatric Inventory(NPI),and anxiety and depression scale.The basic clinical data of the patients were registered,including age,gender,years of education,duration of disease,family history,and long-term residence address.Among them,192 patients diagnosed with probable AD,including 84 cases with early-onset(onset age less than 65 years old)Alzheimer’s disease(EOAD),and 108 cases with late-onset(onset age over 65 years old)Alzheimer’s disease(LOAD).Demographic and neuropsychological data were compared between these two groups of patients by SPSS 23.0 software.Results:1.There were 84 patients in EOAD group,including 31 males and 53 females,with an average age of(58.32 ± 5.35)years;years of education were(8.26 ± 4.99)years;duration of disease was(2.29 ± 1.46)years;24 patients had a family history(28.57%);urban: rural = 1.47:1.In the LOAD group,there were 108 patients,48 males,and 60 females,with an average age of(74.66 ± 5.96)years;years of education were(9.02 ± 4.95)years;duration of disease was(2.03 ± 1.14)years;22 patients had a family history(20.37%);urban: rural = 1.92:1.There was a significant difference in age between the two groups(P < 0.001),and no significant difference in other aspects(P > 0.05).2.MMSE,Mo CA,CDT,BNT-30,total ADL,total NPI,and caregiver distress scores showed no significant differences between the two groups(P > 0.05).3.The EOAD group had the highest score of depression and the LOAD group had the highest score of abnormal motor behavior.The incidence of depression was the highest in both groups.The sub-scores of depression and apathy of the EOAD patients were higher than those of the LOAD patients(P = 0.013,P = 0.004),while apathy was significantly more common in the EOAD group than the LOAD group(53.57% vs.32.41%,P = 0.003).4.Stratified analysis according to the disease duration(≤1 year,1-2 years,2-3 years,and >3 years),there was no significant difference in the distribution of the disease duration between the two groups(P > 0.05).At each stage of disease duration,there was no significant difference in MMSE,CDT,BNT-30,ADL,and NPI scores between EOAD and LOAD groups(P > 0.05).5.The total NPI score of the EOAD patients was negatively correlated with MMSE,CDT,and BNT-30 scores,and was positively correlated with ADL score(P < 0.05),while that of the LOAD patients was negatively correlated with MMSE and BNT-30 scores,and was positively correlated with ADL score(P < 0.05).Caregiver distress score was positively correlated with NPI total scores in both groups(P < 0.05).Conclusion: EOAD and LOAD patients showed similar performance in cognitive assessment and overall assessment of activities of daily living.Patterns of neuropsychiatric symptoms impairment were different between the EOAD and the LOAD patients,with more serious depression and apathy and higher incidence of apathy in the EOAD patients.Moreover,the neuropsychiatric symptoms in EOAD patients were related to the impairment of various cognitive domains.Part Two Comparison of impairment in activities of daily living between early-onset and late-onset Alzheimer’s diseaseObjective:To compare the characteristics of activities of daily living(ADL)impairment between early-onset and late-onset Alzheimer’s disease(AD).Methods:From October 2018 to February 2021,192 patients diagnosed as probable AD were recruited from the Department of Neurology in our hospital,including 84 cases of early-onset AD(EOAD,onset age below 65 years old),and 108 cases of late-onset AD(LOAD,onset age above 65 years).All patients underwent neuropsychological tests such as Mini-Mental State Examination(MMSE),Clock Drawing Test(CDT),Boston Naming Test(BNT),Neuropsychiatric Inventory(NPI),Activities of Daily Living Scale(composed of Physical Self-maintenance Scale,PSMS,and Instrumental Activities of Daily Living Scale,IADL).Demographic data and ADL damage characteristics of the two groups were statistically analyzed by SPSS 23.0 software.Results:1.There were 84 cases in the EOAD group,with an average age of(58.32 ± 5.35)years.There were 108 cases in the LOAD group,with an average age of(74.66 ± 5.96)years.There was a significant difference in age between the two groups(P < 0.001).There was no significant difference in other demographic information(sex ratio,years of education,family history,and duration of disease)(P > 0.05).2.There was no significant difference in cognitive performance(MMSE,CDT and BNT)and neuropsychiatric symptoms(NPI)between EOAD and LOAD patients(P > 0.05).3.There was no significant difference between EOAD and LOAD patients in ADL total score and overall damage rate(P > 0.05).4.In PSMS assessment,there was no significant difference in the overall damage rate and severity of PSMS impairment between EOAD patients and LOAD patients.In PSMS sub-items,dressing ability was the most common and seriously damaged in EOAD patients,while bathing ability was the most common and seriously damaged in LOAD patients.The severity and damage rate of dressing ability decline in EOAD patients were significantly higher than those in LOAD patients(P = 0.008,P = 0.006).5.In IADL assessment,the overall damage rate of IADL in LOAD patients was significantly higher than that in EOAD patients(P = 0.019).For IADL sub-items analysis,the impairment of the ability to take a bus and manage personal finance was the most common and the most serious in both groups.The severity and damage rate of the ability to be at home alone in EOAD patients were significantly higher than those of LOAD patients(P = 0.029,P = 0.031).The severity of functional impairment in medication management in LOAD patients was significantly higher than that in EOAD patients(P = 0.037).6.In IADL independence analysis,the decline of the independence for taking a bus and managing personal finance was most common in two groups.The proportion of patients with EOAD who needed help in the laundry was significantly lower than that in patients with LOAD(P = 0.006).7.ADL scores were significantly associated with MMSE,CDT,and BNT scores(P < 0.001).In the correlation analysis between ADL scores and 12 sub-items of NPI,delusion,hallucination,anxiety,apathy,irritability,abnormal motor behavior,sleep disturbances/night behavior,appetite disturbances/eating disorder were related to impairment in ADL in EOAD group(P < 0.05).Delusion,euphoria,apathy,disinhibition,abnormal motor behavior,and sleep/night behavior were related to impairment in ADL in LOAD group(P < 0.05).Conclusion:Patterns of ADL impairment were different between EOAD and LOAD patients.The overall damage rate of IADL and the impaired degree of medication management ability in LOAD patients were higher than that in EOAD patients,but the impairment of ability in dressing and staying at home alone in EOAD patients was more obvious than those in LOAD patients,and the ability to do laundry independently was better preserved.The ADL dysfunction in both groups was related to cognitive impairment and neuropsychiatric symptoms.Part Three Texture analysis on amyloid PET images of early-onset and late-onset Alzheimer’s diseaseObjective: To analyze the difference of texture features between early-onset and late-onset Alzheimer’s disease(AD)on Aβ amyloid positron emission tomography(Aβ-PET)images and to evaluate the correlation between Aβ-PET image texture features and neuropsychiatric symptoms.Methods: The data of Aβ-PET(18F-AV45 PET)images of patients with probable AD in the AD neuroimaging database(ADNI)were analyzed.Eighty-seven patients with Aβ-PET-positive AD were recruited in this study,including 35 patients with early-onset AD(EOAD,younger than 65 years old)and 52 patients with late-onset AD(LOAD,older than 65 years old).The basic information and neuropsychological assessment results were sorted out.From November 2019 to July 2021,28 patients with AD had positive 18F-AV45 PET images in our hospital,including 15 cases with EOAD and 13 cases with LOAD.All patients completed a series of neuropsychological assessments.The 12 symptoms in Neuropsychiatric Inventory(NPI)were divided into three sub-domains: affective symptoms(depression,anxiety,apathy),behavioral disorders,and hyperactivity symptoms(agitation,euphoria,disinhibition,irritability,abnormal motor behavior,sleep/night behavior,appetite/eating disorder),and psychosis symptoms(delusion,hallucination).Texture analysis was adopted to process the Aβ-PET images.Orthogonal partial least squares discriminant analysis(OPLS-DA)in Simca software was employed to compare EOAD and LOAD patients’ texture parameters.Texture biomarkers were screened according to OPLS-DA S-plot.SPSS 23.0 software was used to analyze the correlation between texture features and neuropsychiatric symptoms of the two groups,and then the regression model was established and corrected.Results:1.In the ADNI database,there were 35 cases in the EOAD group,with an average age of(62.52 ± 4.05)years.There were 52 cases in the LOAD group,with an average age of(78.47 ± 2.10)years.There was a significant difference in the age of onset between the two groups(P < 0.001),and there was no significant difference in other demographic characteristics(sex ratio,years of education,left-right handedness ratio,racial composition ratio,family history,proportion of APOE ε4 positive,duration of disease)(P > 0.05).2.In the ADNI database,there was no significant difference in neuropsychological assessment between the two groups(P > 0.05).The CDR score of all patients was 0.5 or 1.They were all mild AD patients.3.In our center,there were fifteen cases in the EOAD group,with an average age of(56.67 ± 4.75)years.There were thirteen cases in the LOAD group,with an average age of(71.62 ± 4.37)years.There was a significant difference in age between the two groups(P < 0.001).There was no significant difference in other demographic information and neuropsychological assessment results(P > 0.05).The impairment in cognitive function and neuropsychiatric symptoms were more severe in patients from this center than those from ADNI.4.In the ADNI database,OPLS-DA analysis showed significant differences in EOAD and LOAD patients’ overall texture features.The texture feature parameters(higher order statistics: entropy of gray level dependence matrix)of bilateral globus pallidus and right insula were the best biomarkers to distinguish the two groups.In the EOAD group,there were multiple texture parameters from various brain regions in the temporal lobe and frontal lobe,strongly correlated with the total score of NPI and each subdomain’s symptoms.In the LOAD group,no similar strong correlation was observed.The texture features of the right fusiform gyrus and the right medial orbital gyrus were independent influencing factors of the severity of NPI in EOAD patients.5.In our research center,we found that there were also significant differences in the texture features of Aβ-PET images between the two groups.The texture feature parameters of the frontal lobe(left anterior subgenus frontal cortex)and basal ganglia area(left putamen and left globus pallidus)were the best biomarkers to distinguish the two groups.Conclusion: EOAD and LOAD patients had different texture characteristics of Aβ-PET images,and there was a significant difference in the features of Aβ deposition in the brain.The basal ganglia(globus pallidus)might provide a pathophysiological basis for the difference of clinical characteristics between EOAD and LOAD patients.With the progress of the disease,the difference of Aβ deposition characteristics in the frontal lobe could gradually appear.In the early stage of EOAD,there was a strong correlation between Aβ deposition and neuropsychiatric symptoms,which could be the evidence why neuropsychiatric symptoms were more common and severe in EOAD patients than that in LOAD patients.