Frontotemporal lobe dementias (FTLD) represent a constellation of disorders that may be overlooked or misdiagnosed, despite being a fairly common presenile neurodegenerative diseases. Although the cognitive disorder can be difficult to document, particularly early in the dementia course, neuropsychological evaluation can assist in the diagnosis. Neuropsychologists are in an excellent position to draw from related disciplines like personality theory and social psychology to better assess the types of changes that characterize the prodromal and early phases of the disease. This review summarizes the current state of the field in the diagnosis of FTLD and discusses the emerging role of neuropsychology in elucidating the brain organization of complex processes including empathy, behavioral control and inhibition, reward systems, appetitive behaviors, emotional regulation, and goal-orientation. As this review underscores, FTD remains a powerful model for studying brain-behavior relationships.Frontotemporal lobar degeneration (FTLD) refers to a set of neurodegenerative disorders arising from relatively circumscribed frontal and temporal lobar atrophy. Characterized by troubling and progressive changes in behavior, personality, judgment, language, and cognition, the disorder compromises individuals while still in their productive years and may initially be mistaken as a psychiatric disorder. As with other degenerative dementias, a goal is to identify these disorders early with the intent of intervening before the disease has fully expressed in brain. Although no pharmacological treatments are yet available to prevent the disease progression, there are treatments that help alleviate symptoms and nonpharmacological interventions to deal with problem behaviors, coping, and adjustment. From a cognitive neuroscience perspective, the FTLD dementias with their effects on some of the core features of human personality and cognition offer an opportunity to better understand how these fundamental processes of human existence are functionally organized, both the processes involved as well as the brain systems that mediate them. This review article discusses the clinical presentation of the FTLD dementias with an emphasis on its early expression. We propose that by applying a theoretical framework of human behavior from social psychology and constructs from personality theory to the study of FTLD, neuropsychology is ideally positioned to elucidate some of the brain mechanisms underlying a range of complex human behaviors, emotions, and social cognition. Clinical and Neuropathological Expression of FTLDThe first mention of FTLD as a syndrome was in 1892 when Arnold Pick, a neurologist at the University of Prague, described the clinical and pathological features of one of his patients. He reported an aphasic presentation that progressed over three years in a 71-yearold individual. Upon autopsy, there was found to be significant frontal and temporal lobe atrophy in the diseased brain. Pick's clinical description of his patien...

Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72−) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN−) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subject's family. Mean age of C9orf72+ and C9orf72− were 42.6 ± 11.3 and 49.7 ± 15.5 years, respectively; while GRN+ and GRN− groups were 50.1 ± 8.7 and 53.2 ± 11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72− and GRN− combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease.

Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature.

The purpose of this pilot study was to compare the performance of patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) on cognitively-based daily living tasks. The hypothesis was that patients with TLE would demonstrate relatively more impairment on a test of everyday memory, while patients with FLE would demonstrate relatively more impairment on a test of everyday executive function. The five Daily Living subtests of the Neuropsychological Assessment Battery (NAB) were administered to twentyfive patients with TLE and nine patients with FLE. The two groups were matched on all demographic variables. The hypothesis was not confirmed: the TLE and FLE patient groups did not demonstrate a double dissociation in memory and executive daily functioning. Rather, both groups were significantly impaired in daily memory functioning, while their executive daily functioning test scores were within normal limits. Relative deficits were also noted in attention in the TLE group and in language in the FLE group, suggesting that despite having focal lesions, functional impairments may be seen in a broad range of daily activities in these patient groups. Generalizability of the findings is limited due to the small number of subjects and because the everyday cognition measures employed may not have been adequately sensitive. Future studies are needed with larger sample sizes to provide a better understanding of how cognitive impairment in epilepsy is associated with deficits in daily functioning.