Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.
BACKGROUND
Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI).


METHODS
Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD.


RESULTS
Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD.


CONCLUSIONS
This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Mario
M
Torso
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Laura
L
Serra
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Giovanni
G
Giulietti
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Barbara
B
Spanò
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Elisa
E
Tuzzi
Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, IRCCS, Rome, Italy; Department of Neuroscience, University of Rome 'Tor Vergata', Rome, Italy.
Giacomo
G
Koch
Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, IRCCS, Rome, Italy; Department of Neuroscience, University of Rome 'Tor Vergata', Rome, Italy.
Carlo
C
Caltagirone
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy; CISC, Brighton & Sussex Medical School, Brighton, United Kingdom.
Mara
M
Cercignani
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
Marco
M
Bozzali
D000368:Aged; D000544:Alzheimer Disease / Q000523:psychology*; D057565:Apathy; D001284:Atrophy / Q000473:pathology; D001519:Behavior; D001931:Brain Mapping; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000523:psychology; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D013788:Thalamus / Q000473:pathology*; D066127:White Matter / Q000473:pathology