Nonmotor symptoms (NMS) in Parkinson's disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty-one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time-spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2-year premotor period. Those reported more frequently in the 2- to 10-year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream-enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms-constipation, cognition-related, mood-related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition-related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls.

Early-onset and late-onset Alzheimer's disease (EOAD and LOAD) are two forms of the disease with the same characteristic neuropathological hallmarks. However, higher burdens of neuritic plaques and neurofibrillary tangles in frontal and parietal lobes have been found in EOAD than in LOAD patients. Thus, the EOAD subjects may have a differentiated clinical presentation compared to the LOAD ones. Some authors have found less hippocampal memory presentations and more focal cortical abnormalities (such as visuoconstructive or executive dysfunction) in EOAD than LOAD patients. The aim of the present study was to determine which initial clinical profiles differ between EOAD and LOAD; and to analyze whether another age cut-off could discriminate better between EOAD and LOAD clinical presentations than the conventional limit of 65. All patients fulfilling NINCDS-ADRDA criteria for probable Alzheimer's disease who referred to our Hospital between October 2007 and December 2012 were included in the study. The conventional age limit of 65 was established to distinguish between EOAD and LOAD. Baseline neuropsychological scores, adjusted for age and education, were compared between both groups. A total of 181 patients (38 EOAD, 143 LOAD) entered in the analysis. Sex distribution and time of evolution of symptoms did not differ between groups. The EOAD patients performed worse than LOAD in attentional, imitation praxis and verbal learning tests. In addition, the age cut-off of 70 was found to differentiate between early- and late-onset groups better than the standard cut-off of 65 years old. Our results support a differentiated neuropsychological impairment pattern in EOAD compared to LOAD.