Neuropsychological,behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: A longitudinal and post-mortem single case analysis

We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that left and right anterior temporal lobes serve as semantic hubs that may be affected differentially in semantic variant by early, relatively unilateral damage.     

Progressive prosopagnosia at a very early stage of frontotemporal lobar degeneration

Background: The present paper describes a patient with a right temporal lobe variant (RTLV) of frontotemporal lobar degeneration (FTLD). Methods: The study was undertaken when the patient was completely independent in her environment and had not complained of any cognitive problems. Results: Under general neuropsychological assessment, the patient showed no notable deficit other than a difficulty in recognizing famous people by looking at photographs of their faces. Subsequent in‐depth evaluation indicated prosopagnosia: the patient presented with an impaired ability to recognize the faces of famous people and family members, whereas her visuospatial abilities were intact. Because the patient was able to recognize familiar people by their voices, the impairment was not a general loss of knowledge about people, but an inability to access this knowledge from visual stimuli (i.e. via the visual modality). The patient also exhibited a ‘within‐category’ learning deficit; however, her ability to learn from ‘across‐category’ visual stimuli remained intact. Conclusions: Overall, the results of the present study support the proposed model of RTLV of FTLD, where the first sign would be the disruption of face recognition components, leading to a selective form of associative prosopagnosia. Further, the co‐occurrence of face and ‘within‐category’ object learning deficits favor an interpretation in which a more generalized deficit occurs ‘earlier’ in the sequence of events associated with the object recognition process.     

Right Temporal Lobe Atrophy: A Case That Initially Presented as Excessive Piety

Objective: Variants of frontotemporal lobar degeneration (FTLD) are associated with distinct clinical, pathological, and neuroanatomical profiles. Lines of emerging research indicate a rare variant with focal atrophy of the right temporal lobe (RTLA). The objective was to present case data and discussion of an individual with RTLA in order to assist with conceptualization of this variant. Method: A 60-year-old, right-handed, college-educated Protestant minister with RTLA was evaluated. This patient presented with several hallmark behavioral and psychiatric features with personality changes, including hyper-religiosity, depression, and social disinhibition. Given the profession of the patient, the observed personality alterations (e.g., religiosity and pietism) were initially excused, which delayed diagnosis. Results: In addition to cognitive deficits, an examination of affect processing within visual and auditory channels revealed severe impairment in emotion recognition with features of prosopagnosia. These impairments were in general more severe than the cognitive impairment observed on traditional neuropsychological measures. Conclusions: This case provides support for an FTLD right temporal lobe variant. This case also illustrates the importance of neuropsychological evaluation of affect processing in the differential diagnosis and treatment planning for FTLD and its subtypes.     

The right temporal lobe variant of frontotemporal dementia

The right temporal variant of frontotemporal lobar degeneration (Rtv-FTLD) is a focal degenerative condition affecting predominantly the right temporal lobe. The aim of this study was to further characterize the profile of cognitive impairment and the neuroanatomical basis of Rtv-FTLD patients without behavioural disturbances. A group of three patients with this syndrome had a detailed neuropsychological assessment, along with Voxel-Based Morphometry (VBM) of their brain to determine location of cortical atrophy. VBM analyses showed a pattern of atrophy that was predominant in the right hemisphere and concerned primarily the right anterior temporal lobe region. Patients carried out a test of famous people in which their ability to recognize, name and provide semantic information about famous persons from their faces, their voices and their names was investigated. They all showed a severe defect in recognizing, naming and identifying famous people irrespective of modality. Therefore, their inability to recognize famous people resulted from a multimodal defect (semantic). These results highlight the semantic nature of the defect, and suggest that the anterior right temporal lobe may have a prominent role in processing person-based semantic knowledge. This study helps in further understanding the neuropsychological profile of patients with Rtv-FTLD.     

Different patterns of famous people recognition disorders in patients with right and left anterior temporal lesions: a systematic review

Selective disorders in recognition of familiar people have been described in patients with right and left anterior temporal lesions, but the exact nature of these cognitive impairments remains controversial. A clarification of this issue could have theoretical implications, because, according to Snowden et al. [Snowden, J. S., Thompson, J. C., & Neary, D. (2004). Knowledge of famous faces and names in semantic dementia. Brain, 127, 860-872], the pattern of impairment shown by patients with right and left anterior temporal atrophy is inconsistent with unitary, abstract, amodal models of semantic memory. This pattern could, on the contrary suggest a multimodal network, in which the right and left temporal lobes would mainly process and store visual and, respectively, verbal information. I tried to clarify this issue by systematically reviewing: (a) all published individual cases of patients showing a prevalent damage of the anterior parts of the right or left temporal lobes and a selective disorder of famous people recognition; (b) all group studies of patients with right or left temporal lobe epilepsy, which had investigated aspects of famous people recognition impairment. Results of these reviews consistently showed that different patterns of impaired recognition of familiar people can be observed in patients with right and left anterior temporal pathology. These patterns consist of a loss of familiarity feelings and of person specific information retrieval from face stimuli, when the right temporal lobe is damaged and of a prevalent impairment in finding their names when the anterior parts of the left temporal lobe are selectively damaged.     

Right temporal variant frontotemporal dementia with motor neuron disease

Patterns of atrophy in frontotemporal dementia (FTD) correlate with the clinical subtypes of behavioral variant FTD (bvFTD), semantic dementia, progressive non-fluent aphasia (PNFA) and FTD with motor neuron disease (FTD-MND). Right temporal variant FTD is associated with behavioral dyscontrol and semantic impairment, with tau abnormalities more common in right temporal bvFTD and TDP-43 accumulation in right temporal semantic dementia. However, no clinical and anatomical correlation has been described for patients with predominant right temporal atrophy and FTD-MND. Therefore, we performed a database screen for all patients diagnosed with FTD-MND at Mayo Clinic and reviewed their MRI scans to identify those with striking, dominant, right temporal lobe atrophy. For cases with volumetric MRI we performed voxel based morphometry and for those with brain tissue we performed pathological examination. Of three such patients identified, each patient had different presenting behavioral and/or aphasic characteristics. MRI, including diffusion tensor imaging in one patient, and FDG positron emission tomography revealed striking and dominant right temporal lobe atrophy, right corticospinal tract degeneration, and right temporal hypometabolism. Archived brain tissue was available in two patients; both demonstrating TDP-43 type 3 pathology (Mackenzie scheme) with predominant neuronal cytoplasmic inclusions. In one case, neurofibrillary tangles (Braak V) and neuritic plaques were also present in keeping with a diagnosis of Alzheimer’s disease. There appears to be an association between FTD-MND and severe right temporal lobe atrophy. Until further characterization of such cases are determined, they may be best classified as right temporal variant FTD-MND.     

Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is an uncommon degenerative dementia that presents with focal cognitive and behavioral deficits. OBJECTIVE: To determine the correlation of the different presentations of FTLD with structural neuroimaging findings. DESIGN AND PATIENTS: In a blinded study, we retrospectively evaluated the clinical presentations and magnetic resonance imaging (MRI) patterns of atrophy in 59 patients with FTLD and 26 patients with probable Alzheimer disease at a memory disorders clinic. RESULTS: Analysis of variance revealed a significant difference in the patterns of atrophy in the FTLD and Alzheimer disease groups. Patients with FTLD presenting with altered personal conduct had significant bifrontal atrophy, whereas patients presenting with semantic dementia had significant left temporal and bifrontal atrophy compared with other groups. Disinhibited behavior and hyperphagia correlated with right frontal atrophy, and fluent, anomic aphasia correlated with left temporal atrophy. CONCLUSIONS: We found that the type of clinical presentation of FTLD correlates with specific areas of atrophy. Our method of analysis may be useful to elicit further anatomic-behavioral relationships in degenerative brain disorders.     

Exploring the Role of the Right Temporal Lobe in Person-specific Knowledge: A Case Study of Semantic Dementia Associated with Right Temporal Lobe Atrophy

Abstract : The role of the right temporal lobe in person-specific knowledge is not yet fully understood. We report here the case of a 66-year old, right-handed woman with severe right temporal lobe atrophy, who was diagnosed as having semantic dementia according to established criteria. While she had difficulty in identifying faces of famous people, family members, such as her daughter, were relatively well recognized. Brain MRI revealed asymmetrical lateral temporal lobe atrophy, involving the pole and the inferior and middle temporal gyri on the right side. We examined her knowledge of personal acquaintances and famous people using detailed autobiographical memory and famous events-people tests. While she had lost almost all knowledge of personal acquaintances (e.g., old friends) and famous people of her past, she was able to identify personal acquaintances (e.g., grandchildren) from her recent life, not only by name, but also by face. However, famous people in recent memory could be recognized only by name, but not by face. These results suggest that knowledge regarding personal acquaintances in recent memory is supported by greater exposure, relative to that of famous persons and personal acquaintances in her past life, and the preservation of episodic memory. The right temporal lobe may play an important role in the storage of knowledge about people in past memory and accessing faces of famous people in recent memory.     

What the study of voice recognition in normal subjects and brain-damaged patients tells us about models of familiar people recognition

In recent years it has been shown that a disorder in recognizing familiar people can be observed in patients with lesions affecting the anterior parts of the temporal lobes and that these disorders can be multi-modal, simultaneously affecting the visual, auditory and linguistic channels that allow person identification. Several authors have also shown that patients with right anterior temporal atrophy are more impaired in assessing familiarity and in retrieving person-specific semantic information from faces than from names, whereas the opposite pattern of performance can be observed in patients with left temporal lobe atrophy. Voice recognition disorders have been studied much less even despite their clinical and theoretical importance. The aim of the present review, therefore, was to compare recognition of familiar faces and voices, taking into account not only results obtained in individual patients with right anterior temporal lesions, but also those of group studies of unselected right- and left brain-damaged patients and results of experimental investigations conducted on face and voice recognition in normal subjects. Results of the review showed that: (1) voice recognition disorders are mainly due to right temporal lesions, similarly to face recognition disorders; (2) famous voice recognition disorders can be dissociated from unfamiliar voice discrimination impairments; (3) although face and voice recognition disorders tend to co-occur, they can also dissociate and in these patients there is a prevalent involvement of the right fusiform gyrus when face recognition disorders are on the foreground, and of the right superior temporal gyrus when voice recognition disorders are prominent; (4) normal subjects have greater difficulty evaluating familiarity and drawing semantic information from the voices than from the faces of celebrities. These data are at variance with models which assume that familiarity feelings may be generated at the level of person identity nodes (PINs) and that the latter may be considered as modality-free gateways to single semantic systems in which information about people is stored in an amodal format.     

Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease

BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early characteristic of Alzheimer's disease. However, hippocampal atrophy may also occur in other dementias, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia, 13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for repeated measures showed an effect of diagnostic group on hippocampal volume. There was a significant diagnosis by side (left v right) interaction. Both FTLD and Alzheimer's disease showed hippocampal atrophy compared with controls. Results of the visual MTA rating scale confirmed these findings. Within the FTLD subtypes there were marked differences in hippocampal atrophy. Frontotemporal dementia and semantic dementia showed bilateral hippocampal atrophy, and in semantic dementia the left hippocampus was smaller than in Alzheimer's disease. No significant hippocampal atrophy was detected in non-fluent progressive aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD show different patterns of hippocampal atrophy.     

Brain correlates of musical and facial emotion recognition: evidence from the dementias

The recognition of facial expressions of emotion is impaired in semantic dementia (SD) and is associated with right-sided brain atrophy in areas known to be involved in emotion processing, notably the amygdala. Whether patients with SD also experience difficulty recognizing emotions conveyed by other media, such as music, is unclear. Prior studies have used excerpts of known music from classical or film repertoire but not unfamiliar melodies designed to convey distinct emotions. Patients with SD (n = 11), Alzheimer's disease (n = 12) and healthy control participants (n = 20) underwent tests of emotion recognition in two modalities: unfamiliar musical tunes and unknown faces as well as volumetric MRI. Patients with SD were most impaired with the recognition of facial and musical emotions, particularly for negative emotions. Voxel-based morphometry showed that the labelling of emotions, regardless of modality, correlated with the degree of atrophy in the right temporal pole, amygdala and insula. The recognition of musical (but not facial) emotions was also associated with atrophy of the left anterior and inferior temporal lobe, which overlapped with regions correlating with standardized measures of verbal semantic memory. These findings highlight the common neural substrates supporting the processing of emotions by facial and musical stimuli but also indicate that the recognition of emotions from music draws upon brain regions that are associated with semantics in language.     

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.     

Rates of hemispheric and lobar atrophy in the language variants of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder which presents with either behavioral or language impairment. The two language syndromes are known as progressive nonfluent aphasia (PNFA) and semantic dementia (SEMD). While cross-sectional imaging patterns of brain atrophy are well-described in FTLD, fewer studies have investigated longitudinal imaging changes. We measured longitudinal hemispheric and lobar atrophy rates using serial MRI in a cohort of 18 patients with PNFA and 17 patients with SEMD as well as 14 cognitively-normal control subjects. We subsequently calculated sample size estimates for clinical trials. Rates of left hemisphere atrophy were greater than rates of right hemisphere atrophy in both PNFA and SEMD with no significant differences between the groups. The disease groups showed asymmetrical atrophy (more severe on the left) at baseline with significantly increasing asymmetry over time. Within a hemisphere, the fastest rate of atrophy varied between lobes: in SEMD temporal > frontal > parietal > occipital, while in PNFA frontal > temporal/parietal > occipital. In SEMD, using temporal lobe measures of atrophy in clinical trials would provide the lowest sample sizes necessary, while in PNFA left hemisphere atrophy measures provided the lowest sample size. These patterns provide information about disease evolution in the FTLD language variants that is of both clinical and neurobiological relevance.     

Hemispheric dominance for emotions, empathy and social behaviour: evidence from right and left handers with frontotemporal dementia

Although evidence from primates suggests an important role for the anterior temporal cortex in social behaviour, human research has to date concentrated almost solely on the orbitofrontal cortex and amygdala. By describing four cases of the temporal variant of frontotemporal dementia we show how this degenerative condition provides an excellent model for investigating the role of the anterior temporal lobe, especially the right, in emotions, empathy and social behaviour. Assessments of semantic memory, processing of emotional facial expression and emotional prosody were made, empathy was measured, and facial expressions of emotion were coded. Of the two right handers described, one subject with predominantly left temporal lobe atrophy had severe semantic impairment but normal performance on all emotional tasks. In contrast, the subject with right temporal lobe atrophy showed severely impaired recognition of emotion from faces and voices that was not due to semantic or perceptual difficulties. Empathy was lost, interpersonal skills were severely affected and facial expression of emotion was characterized by a fixed expression that was unresponsive to situations. Additionally, two left handers with right temporal lobe atrophy are described. One demonstrated the same pattern of hemispheric lateralization as the right handers and had emotional impairment. The other left hander showed the opposite pattern of deficits, suggesting a novel presentation of anomalous dominance with reversed hemispheric specialization of semantic memory and emotional processing.     

A case of Gogi aphasia with predominantly left temporal and parietal lobe atrophy]

We report a 68-year-old right-handed Japanese woman who had a history of progressive difficulty in understanding speech and naming. Neuropsychological examination presented Gogi (word meaning) aphasia and impairment of semantic memory for some common objects. She also presented acalculia and mild constructional impairment. There was no evidence of impairment in elementary perception and motor skills. Her memory performance of visual task was within normal range. She had neither personality change nor behavioral disorder. Magnetic resonance (MR) imaging showed atrophy in the left temporal lobe and the left parietal lobe. Single photon emission computed tomography (SPECT) scans demonstrated a decrease of regional cerebral blood flow in the atrophic sites and the left frontal lobe. We pointed out that the atrophy of the parietal lobe was atypical in the early stage of cortical degenerative disease presenting Gogi aphasia, in addition to in the light of classification of Fronto-Temporal Lobar Degeneration (FTLD).     

A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory

The cortical anatomy of 6 patients with semantic dementia (the temporal lobe variant of frontotemporal dementia) was contrasted with that of a group of age-matched normal subjects by using voxel-based morphometry, a technique that identifies changes in gray matter volume on a voxel-by-voxel basis. Among the circumscribed regions of neuronal loss, the left temporal pole (Brodmann area 38) was the most significantly and consistently affected region. Cortical atrophy in the left hemisphere also involved the inferolateral temporal lobe (Brodmann area 20/21) and fusiform gyrus. In addition, the right temporal pole (Brodmann area 38), the ventromedial frontal cortex (Brodmann area 11/32) bilaterally, and the amygdaloid complex were affected, but no significant atrophy was measured in the hippocampus, entorhinal, or caudal perirhinal cortex. The degree of semantic memory impairment across the 6 cases correlated significantly with the extent of atrophy of the left anterior temporal lobe but not with atrophy in the adjacent ventromedial frontal cortex. These results confirm that the anterior temporal lobe is critically involved in semantic processing, and dissociate its function from that of the adjacent frontal region.     

Two cases of frontotemporal dementia with predominant temporal lobe atrophy

Frontotemporal dementia (FTD) is a subtype of frontotemporal lobar degeneration, which also includes semantic dementia (SD) and progressive non‐fluent aphasia. Frontotemporal dementia is characterized by changes in personality and behavioral abnormalities, generally associated with predominant frontal lobe atrophy. Conversely, SD is typically characterized by Gogi (word meaning) aphasia based on semantic memory impairment and is associated with predominant temporal lobe atrophy. However, in the present cases, we diagnosed FTD on the basis of clinical symptoms, such as disinhibition, indifference, and stereotypy, without semantic memory impairment, even though neuroimaging showed predominant temporal lobe atrophy. We suggest that clinical symptoms are the most important cues for an accurate clinical diagnosis and there is no exclusive relationship between the syndrome and atrophy of the temporal lobes.     

Patterns of brain atrophy in frontotemporal dementia and semantic dementia.

OBJECTIVE: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). METHODS: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. RESULTS: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, group showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. CONCLUSIONS: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders.     

Language impairment and semantic memory loss of semantic dementia

Semantic dementia (SD) is a neurodegenerative disease characterized by atrophy of the anterior temporal regions and progressive loss of semantic memory. SD has recently been reported to be associated with a pathologic diagnosis of frontotemporal lobar degeneration (FTLD) with T^ar DNA-binding protein of 43 kDa (TDP-43) immunoreactive inclusions (FTLD-TDP) type 2 by Mackenzie. In the first several years of the disease, SD patients, especially those with left hemisphere-dominant temporal atrophy, present with primary progressive aphasia, in which language deterioration is obvious; however, they do not have other cognitive and behavioral impairments. The language impairment in SD is termed as word meaning aphasia, in which patients experience both word finding difficulties and word recognizing difficulties (two-way anomia). Phonemic cues are not effective in improving anomia. In addition, SD patients do not experience a sense of familiarity with words that they cannot find or recognize. While reading and writing Japanese words, SD patients, except those who also have motor neuron disease, exhibit well-preserved kana (phonogram) processing. However, in the case of kanji, they often exhibit surface dyslexia while reading and also exhibit phonetic miswriting. In the aphasic stage, SD patients can explain what the objects are and can use them appropriately; however, they cannot find or recognize the names of the objects. On progressing to the semantic memory impairment stage, the patients do not exhibit any familiarity with the objects whose names they cannot find or recognize and are unable to appropriately use these objects. Semantic memory impairment in SD is attributed to damage of gray matter and of superior and inferior white matter connections in the anterior temporal lobe.     

Measurements of the amygdala and hippocampus in pathologically confirmed Alzheimer disease and frontotemporal lobar degeneration

BACKGROUND: Differentiating between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) can be difficult, particularly in the earliest stages of the diseases. Patterns of atrophy on magnetic resonance imaging may help distinguish these diseases and aid diagnosis. OBJECTIVE: To assess the diagnostic utility of magnetic resonance imaging-derived amygdala and hippocampal volumes from patients with pathologically proved AD and FTLD. DESIGN: Cross-sectional volumetric magnetic resonance imaging study of the hippocampus and amygdala. SETTING: Specialist cognitive disorders clinic.Subjects Thirty-seven subjects, including 10 patients with pathologically proved AD, 17 patients with pathologically proved FTLD, and 10 age-matched control subjects. MAIN OUTCOME MEASURES: Hippocampal and amygdala volumes. RESULTS: Geometric mean amygdala and hippocampal volumes were, respectively, 15.0% (95% confidence interval [CI], 4.2%-24.5%) and 16.4% (95% CI, 5.9%-25.6%) lower in the AD than in the control group. In FTLD, the equivalent differences were 43.1% (95% CI, 31.9%-52.6%) in the amygdala and 36.1% (95% CI, 27.5%-43.7%) in the hippocampus. Volumes were significantly lower in the FTLD than in the AD group (P<.01 in both regions). Within the FTLD clinical subgroups, there was evidence of a difference in pattern of atrophy with greater asymmetry (left smaller than right) in semantic dementia compared with frontal variant FTLD (P<.001). On average, the left hippocampus was 14% smaller in semantic dementia than in frontal variant FTLD, whereas the right hippocampus was 37% larger. On average, the left amygdala was 39% smaller in semantic dementia than in frontal variant FTLD, whereas the right amygdala was only 1% smaller. CONCLUSIONS: Hippocampal atrophy is not specific to AD or FTLD. However, severe or asymmetrical amygdala atrophy should suggest FTLD. Atrophy patterns follow clinical syndromes rather than pathology.