- Email: [email protected]
Reduced cortical thickness in patients with subjective cognitive decline is related to clinical progression
Podium Presentations: Thursday, July 23, 2015
neuropsychiatric symptoms were coded as present if present at one or more visits and absent if never reported by the caregiver. Mean standard uptake volume ratios (SUVR) using the whole cerebellum as the reference were calculated. Brain amyloidosis was defined as mean SUVR1.27. We used Chi-square statistics to compare neuropsychiatric symptom prevalence between the amyloid positive and amyloid negative groups. Next we examined the association between amyloid status and neuropsychiatric symptoms using logistic regression with fixed effects for baseline diagnosis, amyloid status, their interaction and cognitive decline (defined as transition from NC to MCI or dementia and transition to MCI to dementia in follow up). Results: There were no significant differences in baseline diagnosis, age, sex, education, follow-up duration or time to PET scan between the amyloid positive and amyloid negative groups. Amyloid positive individuals had significantly higher rates of pre-existing anxiety (46 vs. 10%, p¼0.0009) and apathy (42 vs. 20%, p¼0.05) relative to amyloid negative subjects. Presence of anxiety remained significantly associated with brain amyloidosis after adjusting for baseline diagnosis and longitudinal decline (b¼2.5, p¼0.05). NC who tested amyloid positive in follow-up were 12 times more likely to develop anxiety compared to amyloid negative NC. MCI who tested amyloid positive in follow-up were 4 times more likely to develop anxiety compared to amyloid negative MCI. Conclusions: We found a strong association between amyloid pathology and pre-existing anxiety in both our cognitively normal and MCI subjects. Our analyses suggest that NC subjects develop anxiety at a minimum at the time of but potentially even prior to reaching the threshold for amyloid positivity and suggest that anxiety might be one of the first clinical correlates of brain amyloidosis.
O5-02-03
REDUCED CORTICAL THICKNESS IN PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE IS RELATED TO CLINICAL PROGRESSION
Sander Verfaillie1,2, Betty M. Tijms1,2, Adriaan Versteeg1, Femke Bouwman3, Philip Scheltens1,2, Frederik Barkhof1,2, Hugo Vrenken1, Wiesje M. van der Flier1,2, 1VU University Medical Center, Amsterdam, Netherlands; 2Neuroscience Campus Amsterdam, Amsterdam, Netherlands; 3VU Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: It has been suggested that specific regional atrophy, i.e. a cortical Alzheimer’s Disease (AD) signature, occurs up to 10 years before onset of dementia. We aimed to investigate if cortical thinning of AD signature areas, was related to future clinical progression in patients with subjective cognitive decline (SCD). Methods: We included 305 patients with SCD and available MRI and clinical follow-up (1 year) from the Amsterdam Dementia Cohort. At baseline all patients underwent 3DT1 MRI 1 or 3 Tesla scans (n¼184 and n¼121 respectively). Cortical thickness was estimated using Freesurfer (v5.3). The following bilateral global, composite and regional measures (Killiany/Desikan atlas based) were used: mean thickness, AD signature region, consisting of nine areas: angular, precuneus, supramarginal, superior frontal, superior parietal, temporal pole, inferior temporal, medial temporal and inferior frontal cortex. Outcome measure was clinical progression to MCI or dementia. Cox proportional hazard models were used to evaluate cortical thickness in relation to clinical progression over time. All analyses were corrected for age, gender and scanner type. Results: Forty-six percent of the SCD patients
P317
was female (age: 62610, MMSE: 2862). Fifty out of 305 (16.4%) patients showed clinical progression after an average follow-up of 363 years. Loss of mean cortical thickness and average thickness of the AD cortical signature was associated with respectively 5.44 (CI¼1.53-19.34) and 3.14 (CI¼1.04-9.01) increased risk for clinical progression over time. Subsequent forward stepwise Cox regression analyses of the separate AD signature components showed that medial temporal thinning (HR¼3.30, CI¼1.51-7.20) was most strongly associated with clinical progression. Conclusions: Our findings suggest that thinning of the cortical mantle, AD signature region, and specifically localized thinning of the medial temporal cortex are associated with clinical progression in the earliest stages of AD. O5-02-04
MIDDLE-AGED ADULTS WITH SUBJECTIVE MEMORY COMPLAINTS: CLINICAL AND BRAIN STRUCTURAL FEATURES
Elena Rolandi1, Enrica Cavedo1,2,3,4,5, Giovanni Battista Frisoni6,7, Samantha Galluzzi1, 1IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy; 2INSERM U1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France; 3CATI Multicenter Neuroimaging Platform, Paris, France; 4Institut de la Memoire et de la Maladie d’Alzheimer (IM2A), H^opital de la Pitie-Salp^etriere, AP-HP, Paris, France; 5Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; 6University Hospitals and University of Geneva, Geneva, Switzerland; 7IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. Contact e-mail: [email protected] Background: In recent years Subjective Memory Complaints (SMC) in elderly has been investigated as a potential risk factor for cognitive decline. Aim of the present study is to compare socio-demographic, clinical, neuropsychological and brain structural features of middle-aged cognitive intact individuals with and without memory complaints. Methods: 134 middle-aged cognitive intact individuals (49.265.6 years, MMSE 29.1) underwent clinical, neuropsychological evaluation and T1-weighted volumetric MRI. Subjects were considered SMC+ if they believed to have some memory disturbances (yes/no question). MRI images were pre-processed using DARTEL tool in SPM8 to perform Voxel-Based Morphometry analysis. Whole brain gray matter volumes differences between groups were computed using an analysis of variance model with age, gender, education and depressive symptoms as covariates, after correction for total intracranial volume. Comparison of clinical data between groups were performed using independent sample ttest or chi-square test when appropriate. Results: SMC+ (N¼78) compared to SMC- (N¼56) were more female (68% vs 37% p<0.001), had lower education (10.064.0 vs 12.363.9 p¼0.001) and showed more depressive symptoms at Brief Symptoms Inventory (1.0 6 0.8 vs 0.7 6 0.5 p¼0.001). No significant differences in vascular and genetic (Apolipoprotein E4 allele) risk factors and neuropsychological performance were found between groups. SMC+ show significant lower gray matter volumes than SMC- in caudate nuclei and right superior medial frontal gyrus (FWE correction, p<0.05). SMC- did not show any voxel with significantly reduced grey matter density. Conclusions: This is the first study aimed to characterize early subjective memory complainers (age between 40 and 60 years). Follow-up studies should clarify whether structural differences found between groups are normal inter-individual genetically-based features or pathological abnormalities predisposing to the development of Alzheimer’s disease.
neuropsychiatric symptoms were coded as present if present at one or more visits and absent if never reported by the caregiver. Mean standard uptake volume ratios (SUVR) using the whole cerebellum as the reference were calculated. Brain amyloidosis was defined as mean SUVR1.27. We used Chi-square statistics to compare neuropsychiatric symptom prevalence between the amyloid positive and amyloid negative groups. Next we examined the association between amyloid status and neuropsychiatric symptoms using logistic regression with fixed effects for baseline diagnosis, amyloid status, their interaction and cognitive decline (defined as transition from NC to MCI or dementia and transition to MCI to dementia in follow up). Results: There were no significant differences in baseline diagnosis, age, sex, education, follow-up duration or time to PET scan between the amyloid positive and amyloid negative groups. Amyloid positive individuals had significantly higher rates of pre-existing anxiety (46 vs. 10%, p¼0.0009) and apathy (42 vs. 20%, p¼0.05) relative to amyloid negative subjects. Presence of anxiety remained significantly associated with brain amyloidosis after adjusting for baseline diagnosis and longitudinal decline (b¼2.5, p¼0.05). NC who tested amyloid positive in follow-up were 12 times more likely to develop anxiety compared to amyloid negative NC. MCI who tested amyloid positive in follow-up were 4 times more likely to develop anxiety compared to amyloid negative MCI. Conclusions: We found a strong association between amyloid pathology and pre-existing anxiety in both our cognitively normal and MCI subjects. Our analyses suggest that NC subjects develop anxiety at a minimum at the time of but potentially even prior to reaching the threshold for amyloid positivity and suggest that anxiety might be one of the first clinical correlates of brain amyloidosis.
O5-02-03
REDUCED CORTICAL THICKNESS IN PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE IS RELATED TO CLINICAL PROGRESSION
Sander Verfaillie1,2, Betty M. Tijms1,2, Adriaan Versteeg1, Femke Bouwman3, Philip Scheltens1,2, Frederik Barkhof1,2, Hugo Vrenken1, Wiesje M. van der Flier1,2, 1VU University Medical Center, Amsterdam, Netherlands; 2Neuroscience Campus Amsterdam, Amsterdam, Netherlands; 3VU Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: It has been suggested that specific regional atrophy, i.e. a cortical Alzheimer’s Disease (AD) signature, occurs up to 10 years before onset of dementia. We aimed to investigate if cortical thinning of AD signature areas, was related to future clinical progression in patients with subjective cognitive decline (SCD). Methods: We included 305 patients with SCD and available MRI and clinical follow-up (1 year) from the Amsterdam Dementia Cohort. At baseline all patients underwent 3DT1 MRI 1 or 3 Tesla scans (n¼184 and n¼121 respectively). Cortical thickness was estimated using Freesurfer (v5.3). The following bilateral global, composite and regional measures (Killiany/Desikan atlas based) were used: mean thickness, AD signature region, consisting of nine areas: angular, precuneus, supramarginal, superior frontal, superior parietal, temporal pole, inferior temporal, medial temporal and inferior frontal cortex. Outcome measure was clinical progression to MCI or dementia. Cox proportional hazard models were used to evaluate cortical thickness in relation to clinical progression over time. All analyses were corrected for age, gender and scanner type. Results: Forty-six percent of the SCD patients
P317
was female (age: 62610, MMSE: 2862). Fifty out of 305 (16.4%) patients showed clinical progression after an average follow-up of 363 years. Loss of mean cortical thickness and average thickness of the AD cortical signature was associated with respectively 5.44 (CI¼1.53-19.34) and 3.14 (CI¼1.04-9.01) increased risk for clinical progression over time. Subsequent forward stepwise Cox regression analyses of the separate AD signature components showed that medial temporal thinning (HR¼3.30, CI¼1.51-7.20) was most strongly associated with clinical progression. Conclusions: Our findings suggest that thinning of the cortical mantle, AD signature region, and specifically localized thinning of the medial temporal cortex are associated with clinical progression in the earliest stages of AD. O5-02-04
MIDDLE-AGED ADULTS WITH SUBJECTIVE MEMORY COMPLAINTS: CLINICAL AND BRAIN STRUCTURAL FEATURES
Elena Rolandi1, Enrica Cavedo1,2,3,4,5, Giovanni Battista Frisoni6,7, Samantha Galluzzi1, 1IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy; 2INSERM U1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France; 3CATI Multicenter Neuroimaging Platform, Paris, France; 4Institut de la Memoire et de la Maladie d’Alzheimer (IM2A), H^opital de la Pitie-Salp^etriere, AP-HP, Paris, France; 5Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; 6University Hospitals and University of Geneva, Geneva, Switzerland; 7IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. Contact e-mail: [email protected] Background: In recent years Subjective Memory Complaints (SMC) in elderly has been investigated as a potential risk factor for cognitive decline. Aim of the present study is to compare socio-demographic, clinical, neuropsychological and brain structural features of middle-aged cognitive intact individuals with and without memory complaints. Methods: 134 middle-aged cognitive intact individuals (49.265.6 years, MMSE 29.1) underwent clinical, neuropsychological evaluation and T1-weighted volumetric MRI. Subjects were considered SMC+ if they believed to have some memory disturbances (yes/no question). MRI images were pre-processed using DARTEL tool in SPM8 to perform Voxel-Based Morphometry analysis. Whole brain gray matter volumes differences between groups were computed using an analysis of variance model with age, gender, education and depressive symptoms as covariates, after correction for total intracranial volume. Comparison of clinical data between groups were performed using independent sample ttest or chi-square test when appropriate. Results: SMC+ (N¼78) compared to SMC- (N¼56) were more female (68% vs 37% p<0.001), had lower education (10.064.0 vs 12.363.9 p¼0.001) and showed more depressive symptoms at Brief Symptoms Inventory (1.0 6 0.8 vs 0.7 6 0.5 p¼0.001). No significant differences in vascular and genetic (Apolipoprotein E4 allele) risk factors and neuropsychological performance were found between groups. SMC+ show significant lower gray matter volumes than SMC- in caudate nuclei and right superior medial frontal gyrus (FWE correction, p<0.05). SMC- did not show any voxel with significantly reduced grey matter density. Conclusions: This is the first study aimed to characterize early subjective memory complainers (age between 40 and 60 years). Follow-up studies should clarify whether structural differences found between groups are normal inter-individual genetically-based features or pathological abnormalities predisposing to the development of Alzheimer’s disease.