A main challenge of current research on primary degenerative dementia is establishing a causal and temporal link between structural alterations, synaptic and circuit dysfunction, and cognitive decline. Experimental data support the view that the observable symptoms of dementia are only the tip of an iceberg, made up of neuropathological alterations which accu- mulate over time and lead to loss of synaptic connections and dysfunction of cortical circuitry [1].
In the clinical setting, current biomarkers are mainly based on the detection of amyloid deposition and neuronal injury. Increasing evidence also suggests a role for functional neuro- imaging and electrophysiological parameters, derived from functional MRI (fMRI), electroencephalography (EEG), and transcranial magnetic stimulation, as biomarkers of dysfunc- tion of neurotransmission and synaptic plasticity in specific types of primary dementia [2–6].
