Background/Aims: Accurate diagnosis of sporadic early-onset Alzheimer's disease (EOAD) can be challenging, and cerebrospinal fluid (CSF) biomarkers may assist in this process. We compared CSF indices between three EOAD subtypes: amnestic, logopenic progressive aphasia (LPA), and posterior cortical atrophy (PCA). Methods: We identified 21 amnestic EOAD, 20 LPA, and 12 PCA patients with CSF data, which included amyloid β_1-42 (Aβ42), total tau (t-tau), phospho-tau₁₈₁ (p-tau), and Aβ42/t-tau index (ATI) levels. Results: Aβ42 and ATI levels were similar across groups, but t-tau and p-tau levels were significantly lower in PCA patients. Conclusions: The Aβ42 and ATI data confirm the commonality of the Aβ pathology in EOAD. The lower tau indices in PCA patients may reflect differences in the distribution of neurofibrillary tangles or rates of neurodegeneration.

Semantic dementia impairs semantic autobiographical memory, but tends to spare its episodic components that are critical for the sense of self. Investigators have recently discovered disturbances in the “future self” in semantic dementia. We report a 63-year-old man with semantic dementia who was hospitalized after suicide attempts that he attributed to his loss of a sense of future self. He complained of a decreased sense of being human, because he could not imagine doing things in the future that he had done in the past. Suicidal thinking and inability to place himself in future tasks persisted despite resolution of depression. Clinical assessment revealed a crossmodal loss of semantic knowledge, and neuroimaging showed bilateral anterior temporal atrophy and hypometabolism. On specific tests of autobiographical memory, identity, attribute knowledge, and future projection, the patient could return to the past and visualize himself in familiar scenarios, but he could not visualize himself even passively in these scenarios in the future. His future self was impaired not from seeing himself disabled; it was from an absence of semantic details of potential experiences, associated with impaired semantic autobiographical memory. His self-representations were concrete and specific rather than abstract and generalizable. This patient and recent publications indicate that semantic dementia impairs the ability to imagine oneself as capable in the future, leading some patients to suicidal behavior. We discuss possible mechanisms for these findings, including the potential role of abstract construals for future thinking.

Background: Previous cross-sectional studies suggest that assessments of instrumental activities of daily living (IADLs) may be useful for operationalizing the differences in functional deficits seen in mild cognitive impairment (MCI) and dementia. However, their utility for longitudinal changes in IADLs in the transition between MCI and dementia remains unclear. Methods: We analyzed longitudinal IADL data with the Functional Activities Questionnaire (FAQ) in stable (MCI-S; n = 1,318) or progressive (MCI-P; n = 1,108) MCI patients. Results: Larger increases in FAQ scores were seen in the MCI-P group across a 14.5-month interval, but overlapping distributions in the two groups yielded poorer discriminatory power than prior cross-sectional reports. Conclusion: Our findings emphasize the difficulties in operationalizing the criterion of ‘essentially intact' IADLs in MCI, which may complicate the interpretation of disease progression in MCI treatment trials. © 2014 S. Karger AG, Basel

Patients with SD are at special risk of committing suicide, particularly if they have depression and preserved insight. Possible mechanisms include an impaired sense of semantic competence with increased impulsivity.