Bilingualism is thought to confer advantages in executive functioning, thereby contributing to cognitive reserve and a later age of dementia symptom onset. While the relation between bilingualism and age of onset has been explored in Alzheimer's dementia, there are few studies examining bilingualism as a contributor to cognitive reserve in frontotemporal dementia (FTD). In line with previous findings, we hypothesized that bilinguals with behavioral variant FTD would be older at symptom onset compared to monolinguals, but that no such effect would be found in patients with nonfluent/agrammatic variant primary progressive aphasia (PPA) or semantic variant PPA. Contrary to our hypothesis, we found no significant difference in age at symptom onset between monolingual and bilingual speakers within any of the FTD variants, and there were no notable differences on neuropsychological measures. Overall, our results do not support a protective effect of bilingualism in patients with FTD-spectrum disease in a U.S. based cohort.

Frontotemporal dementia (FTD) is a devastating neurodegenerative condition for which there is currently no effective treatment. Although it is much less common than Alzheimer’s disease, the impact of FTD is increased by its relatively early onset and high heritability. Clinical heterogeneity and overlap with other neurodegenerative and psychiatric syndromes complicate diagnosis. However, recent advances in our understanding of the molecular basis of FTD provide a foundation for the development of much-needed biomarkers and targeted therapies. This review provides a summary of the recently revised clinical criteria for FTD, highlights diagnostic challenges, briefly summarizes recent molecular discoveries and then focuses on promising developments in biomarkers and clinical trials.

Alzheimer’s disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common “atypical” clinical presentations, including syndromes dominated by visual, aphasic, “frontal,” or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.

Objective: To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias.Methods: Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer’s disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. Results: The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. Conclusions: A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

The objective of this study was to describe the neuropsychological profiles of the three variants of primary progressive aphasia (PPA). Based on a comprehensive speech and language evaluation, 91 subjects were classified as logopenic (lvPPA=51), semantic (svPPA=13), or agrammatic (agPPA=27). All subjects completed a separate neuropsychological evaluation assessing verbal and visual memory, processing speed, executive function, and visuospatial function. The groups did not differ on demographic variables or on measures of disease duration or aphasia severity. There were group differences on aspects of learning and memory, as well as aspects of executive and visuospatial functions, primarily with the lvPPA group performing lower than the agPPA and svPPA groups. The agPPA group showed subtle deficits consistent with frontal lobe impairment, whereas neurocognitive weaknesses in the svPPA group were restricted to temporal lobe functions. The pattern of neurocognitive dysfunction in lvPPA suggests disease involvement of frontal lobe functions in addition to temporoparietal functions. These neurocognitive findings emphasize the value of a comprehensive neuropsychological evaluation of individuals who present with primary language disturbance, given the pattern of cognitive deficits may provide additive information for differentiating these clinical syndromes. (JINS, 2015, 21, 429–435)

Logopenic progressive aphasia (LPA) is a form of primary progressive aphasia (PPA) characterized by hesitant speech with marked impairment in naming and repetition. LPA is associated with brain atrophy in the left temporal and inferior parietal cortices and is predominantly associated with Alzheimer's disease (AD) pathology. In contrast to LPA, “typical” AD is commonly associated with episodic memory disturbance and bilateral medial temporal lobe atrophy. Recent evidence suggests verbal short-term memory is more impaired than visuospatial short-term memory in LPA. This study investigated verbal and visuospatial short-term memory in 12 LPA and 12 AD patients matched for disease severity, and in 12 age- and education-matched healthy controls. Overall, both patient groups showed significantly reduced verbal and visuospatial spans compared with controls. In addition, LPA patients performed significantly worse than AD patients on both forward and backward conditions of the Digit Span task. In contrast, no difference was present between patient groups on either version of the Spatial Span task. Importantly, LPA patients showed better visuospatial than verbal span whereas AD patients and controls did not differ across modality. This study demonstrates the specificity of the short-term memory disturbance in LPA, which arises from a breakdown of the phonological system. (JINS, 2012, 19, 1–7)

Mutations in the progranulin (PGRN) gene have been identified as a cause of frontotemporal dementia (FTD). However, little is known about the neuropsychological abilities of asymptomatic carriers of these mutations. The aim of the study was to assess cognitive functioning in asymptomatic c.709-1G>A PGRN mutation carriers. We hypothesized that poorer neuropsychological performance could be present before the development of clinically significant FTD symptoms. Thirty-two asymptomatic first-degree relatives of FTD patients carrying the c.709-1G>A mutation served as study participants, including 13 PGRN mutation carriers (A-PGRN+) and 19 non-carriers (PGRN-). A neuropsychological battery was administered. We found that the A-PGRN+ participants obtained significantly poorer scores than PGRN- individuals on tests of attention (Trail-Making Test Part A), mental flexibility (Trail-Making Test Part B), and language (Boston Naming Test). Poorer performance on these tests in asymptomatic PGRN mutation carriers may reflect a prodromal phase preceding the onset of clinically significant symptoms of FTD. (JINS, 2012, 18, 1086–1090)

Language decline is usually the fastest and predominant change in primary progressive aphasia (PPA). In Alzheimer's disease (AD), it is usually associated with global cognitive deficits. Decreased speech output, reduced conversational initiation, echolalia, and changes in the pragmatics of conversation are seen in the behavioral variant of frontotemporal dementia (FTD-bv), however, the evolution of language disturbance in FTD-bv patients is rarely examined systematically with a standardized language battery. We aimed to longitudinally track the nature of language change in FTD-bv, PPA, and AD using a standardized measure of language functioning. We also explored the nature of language deficits between semantic dementia (SD) patients and the fluent subgroup of PPA patients. The Western Aphasia Battery was administered to 105 AD, 20 FTD-bv, 54 PPA, and 10 SD patients on 2 occasions with approximately 1 year between assessments. Ninety-nine of these patients were examined an additional year. FTD-bv and PPA patients showed a faster language decline than AD patients. The eventual overlap in language functioning in FTD-bv and PPA suggests that these syndromes belong to the same spectrum of disorders. In conclusion, longitudinal language assessment provides us with a unique understanding of the evolution and progression of language deterioration in various dementias. (JINS, 2007, 13, 237–245.)

The clock drawing test (CDT) is a widely used cognitive screening test. It is useful in identifying focal lesions and cognitive deficits in dementia groups. Lately, several studies attempted its use to differentiate between dementia subtypes. Although many studies have examined the CDT in dementia populations, research into the use of clock drawing in frontotemporal dementia (FTD) is limited. We examined quantitative (global) and qualitative (specific error type) differences on the CDT between FTD (n = 36) and Alzheimer's disease (AD; n = 25) patients and controls without dementia (n = 25). Results showed significantly lower overall scores in the dementia groups compared to the control group, whereas FTD patients scored significantly higher than the AD group. On qualitative analysis, the FTD group had fewer stimulus bound responses, conceptual deficits, and spatial or planning errors compared to the AD group. In conclusion, both global and error analysis of the CDT helped discriminate the FTD group from controls and AD patients. (JINS, 2006, 12, 159–165.)