One factor believed to impact brain resilience to the pathological damage of Alzheimer's disease (AD) is the so-called "cognitive reserve" (CR). A critical issue that still needs to be fully understood is the mechanism by which environmental enrichment interacts with brain plasticity to determine resilience to AD pathology. Previous work using PET suggests that increased brain connectivity might be at the origin of the compensatory mechanisms implicated in this process. This study aims to further clarify this issue using resting-state functional MRI. Resting-state functional MRI was collected for 11 patients with AD, 18 with mild cognitive impairment (MCI), and 16 healthy controls, and analyzed to isolate the default mode network (DMN). A quantitative score of CR was obtained by combining information about number of years of education and type of schools attended. Consistent with previous reports, education was found to modulate functional connectivity in the posterior cingulate cortex, whose disconnection with the temporal lobes is known to be critical for the conversion from MCI to AD. This effect was highly significant in AD patients, less so in patients with MCI, and absent in healthy subjects. These findings show the potential neural mechanisms underlying the individual's ability to cope with brain damage, although they should be treated with some caution based on small numbers.

Behavioral and psychological symptoms of dementia (BPSD) are commonly observed over the course of Alzheimer's disease (AD). However, it is unclear whether BPSD are part of AD neuropathology or rather represent a psychological reaction to cognitive disabilities. Using voxel-based-morphometry (VBM), we aimed to clarify this issue by investigating patients with AD at different clinical stages. Twenty-seven patients with AD (12 early [ADe] and 15 moderate [ADm]), 19 with amnestic mild cognitive impairment (a-MCI), and 23 healthy controls underwent MRI scanning at 3T. Assessment of BPSD was done in each patient using the Neuropsychiatric Inventory-12 (NPI-12). VBM was used to investigate changes in grey matter (GM) atrophy across groups, and associations between regional GM volumes and occurrence and severity of BPSD in patients. Mood disorders, anxiety, and agitation were present in both a-MCI and AD, while psychotic symptoms were observed mainly in AD. As expected, VBM showed only limited areas of GM atrophy in a-MCI patients, with a progressive extension in ADe and ADm patients (PFWE-corrected-values < 0.05). Disinhibition was strongly associated with GM volume in bilateral cingulate and right middle frontal gyri, while delusions were associated with GM volume in right hippocampus (PFWE-corrected-values < 0.05). This study confirms that BPSD are present since the earliest AD stages. Interesting associations were found in regions traditionally implicated by AD neuropathology. This suggests that BPSD are likely to represent clinical features of AD and should be regarded for their diagnostic and prognostic value.

IMPORTANCE Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. OBJECTIVE To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. DESIGN, SETTING, AND PARTICIPANTS We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a