Clinical characteristics of frontotemporal patients with symmetric brain atrophy

In this paper we explored patterns of frontal and temporal asymmetry in frontotemporal dementia (FTD) and tried to isolate clinical correlates associated with asymmetry or lack thereof. Volumes of frontal and temporal lobes, hippocampus and entorhinal cortex were measured using magnetic resonance imaging (MRI) in 10 patients with FTD. Age- and cranial size-specific values were computed through linear regression analysis (W-scores). A subgroup of 3 patients with symmetric frontal and temporal atrophy was identified. When compared to patients with asymmetric atrophy, the former had younger age at onset of the disease (p = 0.02), greater overall frontotemporal (p = 0.02) and greater entorhinal atrophy (p < 0.04). Two of the three patients were apolipoprotein E ɛ4 carriers versus none of the asymmetric patients (p = 0.02). The lack of asymmetry in this small sample of FTD patients was associated with greater brain atrophy, younger age at onset, and presence of the ɛ4 allele of apolipoprotein E. The presence of the ɛ4 allele is consistent with the hypothesis of greater vulnerability of the brain in ɛ4 carriers. Received: 15 April 2002 / Accepted: 2 October 2002 Correspondence to Dr. G. B. Frisoni     

Regional brain atrophy in HIV-1 infection: association with specific neuropsychological test performance

Quantified magnetic resonance imaging (MRI) was related to neuropsychological (NP) test scores in an asymptomatic HIV-1 seropositive group, a non-demented AIDS/ARC group, a group of subjects with HIV-1 dementia, and a seronegative control group. The MRIs were quantified using three planimetric measures of brain structure: the bicaudate ratio (a measure of caudate region atrophy), the bifrontal ratio (a measure of frontal region atrophy), and the ventricle to brain ratio (a measure of overall cerebral atrophy). Cognitive performance was assessed with standard NP tests. Significant correlations between the MRI ratios and many of the NP tests were observed. Of the tests grooved pegboard, part B of the trail making test, the verbal fluency test, and the digit span forward were associated with MRI abnormalities. The bicaudate ratio was most closely associated with the NP tests. These findings indicate that ventricular enlargement, especially in the region of the caudate, is closely related to poor NP test performance in HIV-1 infection.     

Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis.

Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1-seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1-seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia.     

Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia

BACKGROUND: The pathologic substrates of frontotemporal dementia (FTD) are difficult to predict in vivo. OBJECTIVE: To determine whether different pathologic substrates of FTD have distinct patterns of regional atrophy on magnetic resonance imaging (MRI). DESIGN: Retrospective case study. SETTING: The Institute of Neurology, University College London, and the Institute of Psychiatry, King's College London.Patients Twenty-one cases of FTD selected on pathologic grounds (9 with ubiquitin-positive [tau- and alpha-synuclein-negative] inclusions [FTD-U], 7 with Pick disease [PiD], and 5 with familial FTD with tau exon 10+16 mutations [tau exon 10+16]) and 20 healthy controls were studied. MAIN OUTCOME MEASURES: Patterns of gray matter atrophy in each group as assessed by voxel-based morphometry (VBM) and a blinded visual assessment of each MRI study. RESULTS: All pathologic substrates were associated with atrophy that involved the inferior and medial temporal and inferior frontal lobes. Additionally, specific VBM signatures were identified for each subgroup: FTD-U was associated with asymmetric (left > right) temporal lobe atrophy, PiD was associated with severe dorsolateral bifrontal atrophy, and tau exon 10+16 was associated with asymmetric (right > left) medial temporal lobe atrophy. The VBM findings were supported by blinded visual assessment. CONCLUSION: These findings suggest that MRI patterns of regional gray matter atrophy constitute signatures of tissue pathology in FTD.     

Social cognition, executive functioning, and neuroimaging correlates of empathic deficits in frontotemporal dementia

The authors investigated aspects of interpersonal sensitivity and perspective-taking in relation to empathy, social cognitions, and executive functioning in 26 frontotemporal dementia (FTD) patients. Behavioral-variant FTD (bvFTD) patients were significantly impaired on caregiver assessments of empathy, although self-ratings were normal. Progressive nonfluent aphasia and semantic-dementia samples were rarely abnormal. In bvFTD, empathy ratings were found to be correlated with social cognition and executive functioning measures, but not depression. Voxel-based morphometry revealed that reduced empathic perspective-taking was related to bifrontal and left anterior temporal atrophy, whereas empathic emotions were related to right medial frontal atrophy. Findings suggest that bvFTD causes multiple types of breakdown in empathy, social cognition, and executive resources, mediated by frontal and temporal disease.     

Neuroimaging features in C9orf72 and TARDBP double mutation with FTD phenotype

Increasing evidence has shown that morphological and functional neuroimaging may help to understand the pathophysiological mechanisms leading to behavioral disturbances in patients with genetic or sporadic frontotemporal dementia (FTD). The C9orf72 expansion was found in association with the N267S TARDBP mutation in two siblings with behavioral-variant FTD (bvFTD). In one of them with very mild dementia, MRI showed symmetric atrophy of temporal, inferolateral and orbital frontal cortex, while [18F]FDG-PET disclosed more extended hypometabolism in dorsolateral and inferolateral frontal cortex, anterior cingulate, and caudate nucleus. Hypometabolism in right lateral and orbital frontal cortex was confirmed also in comparison with a group of sporadic bvFTD patients. These findings appear as the neuroimaging hallmark of double C9orf72 and TARDBP gene mutation with a bvFTD phenotype.     

Rates of global and regional cerebral atrophy in AD and frontotemporal dementia.

OBJECTIVE: Serial registered MRI provides a reproducible technique for detecting progressive cerebral atrophy in vivo and was used to determine if there were differences between the rates of cerebral atrophy in AD and frontotemporal dementia (FTD). METHODS: Eighty-four patients with dementia (54 AD and 30 FTD) and 27 age-matched control subjects each had at least two volumetric MR scans. Serial scans were positionally matched (registered), and brain volume loss was determined by calculation of the brain boundary shift integral. RESULTS: There was a difference between the rates of whole-brain atrophy in patients (mean annual volume loss 2.7% of total brain volume) and in control subjects (mean annual volume loss 0.5%). AD and FTD were associated with different rates of atrophy (mean annual losses 2.4 and 3.2%). The range of atrophy rates in the FTD group (0.3 to 8.0%) greatly exceeded that in the AD group (0.5 to 4.7%). Frontal-variant FTD was associated with a wider range of atrophy rates than temporal-variant FTD. Analysis of regional brain atrophy rates revealed that there was widespread symmetrically distributed cerebral volume loss in AD, whereas in frontal FTD there was greater atrophy anteriorly and in temporal FTD the atrophy rate was greatest in the left anterior cerebral cortex. CONCLUSIONS: Both AD and FTD patients had increased rates of brain atrophy. Whereas the patients with AD were associated with a relatively restricted spread of atrophy rates, the greater spread of rates observed in the patients with FTD may reflect the heterogeneity of disease in FTD, with differences observed between frontal and temporal FTD. Increased rates of whole-brain atrophy did not discriminate AD from FTD, but analysis of regional atrophy rates revealed marked differences between patient groups.     

Topographical patterns of lobar atrophy in frontotemporal dementia and Alzheimer's disease

BACKGROUND/AIMS: Fronto-temporal dementia (FTD) designates a group of relatively common neurodegenerative disorders. The aim of this study was to characterize the patterns of brain atrophy in FTD compared to Alzheimer's disease (AD). METHODS: A novel semiautomatic volumetric MRI analysis method was applied to measure regional brain volumes in FTD (n = 15; behavioural variant n = 9, language variant n = 6) in contrast with AD patients (n = 15) and age-matched controls (NC) (n = 15). FTD and AD patients were matched on demographic measures and Mini Mental State Examination scores. RESULTS: Significant atrophy was present in the frontal and anterior temporal lobes of subjects with FTD compared to AD (p = 0.02; effect size = 1.11) and compared to NC (p < 0.001; effect size = 1.86). Severe atrophy of the left anterior temporal region distinguished the language variant. AD patients, by contrast, did not differ from NC for frontal lobe volume but had smaller anterior temporal lobes (p = 0.03). Both dementia groups had medial temporal lobe atrophy of similar magnitude. A logistic regression model including 4 regional measures correctly classified 100% of subjects. CONCLUSION: FTD can be reliably differentiated from AD by virtue of a topographical pattern of atrophy involving the frontal lobes and anterior temporal regions. Medial temporal lobe volumes do not distinguish FTD from AD.     

Distinct behavioural profiles in frontotemporal dementia and semantic dementia

OBJECTIVE: To test predictions that frontotemporal dementia and semantic dementia give rise to distinct patterns of behavioural change. METHODS: An informant based semistructured behavioural interview, covering the domains of basic and social emotions, social and personal behaviour, sensory behaviour, eating and oral behaviour, repetitive behaviours, rituals, and compulsions, was administered to carers of 41 patients with semantic dementia and with apathetic (FTD-A) and disinhibited (FTD-D) forms of frontotemporal dementia. RESULTS: Consistent with prediction, emotional changes differentiated FTD from semantic dementia. Whereas lack of emotional response was pervasive in FTD, it was more selective in semantic dementia, affecting particularly the capacity to show fear. Social avoidance occurred more often in FTD and social seeking in semantic dementia. Patients with FTD showed reduced response to pain, whereas patients with semantic dementia more often showed exaggerated reactions to sensory stimuli. Gluttony and indiscriminate eating were characteristic of FTD, whereas patients with semantic dementia were more likely to exhibit food fads. Hyperorality, involving inedible objects, was unrelated to gluttony, indicating different underlying mechanisms. Repetitive behaviours were common in both FTD and semantic dementia, but had a more compulsive quality in semantic dementia. Behavioural differences were greater between semantic dementia and FTD-A than FTD-D. A logistic regression analysis indicated that emotional and repetitive, compulsive behaviours discriminated FTD from semantic dementia with 97% accuracy. CONCLUSION: The findings confirm predictions regarding behavioural differences in frontotemporal and semantic dementia and point to differential roles of the frontal and temporal lobes in affect, social functioning, eating, and compulsive behaviour.     

Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease.

The characteristic pathological features of Huntington's disease (HD) are neostriatal atrophy and neuronal loss. Although neuroradiological studies often show caudate atrophy in patients with moderate HD, frequently no caudate atrophy is found early in the illness. There have been no quantitative reports to date on in vivo putamen volume measures in mild HD, although the structure is known to be neuropathologically involved in the illness. We measured volumes of caudate nucleus and putamen and bicaudate ratios (BCR) from magnetic resonance images, blind to diagnosis, in 15 patients with mild HD and 19 age- and sex-matched control subjects using a computerized image analysis system. The region showing greatest atrophy was the putamen, which was reduced 50.1% in mean volume in HD patients compared with control subjects (p less than 0.000001). In contrast, caudate volume was reduced 27.7% (p = 0.004). BCR was increased 28.5% in HD patients (p = 0.0002). Discriminant function analysis was 94% effective in identifying the diagnostic group based on putamen volume alone, whereas caudate measures had considerable overlap. Correction of putamen volume for head size led to 100% separation by group. Putamen measures and BCR correlated with neurological examination scores but caudate volume did not. Volumetric measurement of putamen is a more sensitive indicator of brain abnormalities in mild HD than measures of caudate atrophy.     

Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study

Deep gray matter damage may be an important component of the multiple sclerosis (MS) disease process. We tested whether caudate atrophy occurs in MS, and whether it correlates with conventional MRI or clinical markers of disease progression. Caudate nuclei of 24 MS patients and 10 age-matched healthy controls were traced, normalized, reconstructed and visualized from MRI scans. Normalized bicaudate volume was 19% lower in MS controls ( p< 0.001), an effect that persisted after adjusting for whole-brain atrophy ( p< 0.008). Caudate volume did not correlate with disease duration, physical disability score, whole-brain atrophy, or total T2 hyperintense or T1 hypointense lesion load (all p > 0.05). We conclude that selective caudate atrophy is associated with MS and may occur through direct mechanisms.     

Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI.     

Computed tomography in the assessment of seizure-induced supratentorial neuron loss.

Epilepsy patients develop atrophy of the hippocampus and the cerebellum. Because reports exist, in which diffuse atrophy of the CNS of epilepsy patients is mentioned, we wanted to investigate if computed tomography (CT) can demonstrate a decrease of the cerebral volume correlated with the length of time during which the patients have had seizures. We measured the bifrontal ratio, the bicaudate ratio, the lateral ventricular brain ratio, and the sylvian fissure ratio of the CT images of 124 neurologically intact patients with a duration of epilepsy from 3 months to 39 years. Multiple regression analysis revealed no correlation between the CT indices and the seizure types or the time elapsed from the first seizure to CT. The well-known decrease of the CT measures with advancing age was confirmed: among the women by all four measurements; the men only exhibited significant increases of the sylvian fissure and the bicaudate ratios. If diffuse cerebral atrophy occurs as a complication of epilepsy, it does not reach a degree, which allows it to be visualized by CT.     

Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.

A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.     

Bicaudate index in computerized tomography of Huntington disease and cerebral atrophy.

Ventricular sizes on computerized tomographic (CT) scans were compared in seven patients with Huntington disease, 20 patients with cerebral atrophy, and 20 normal controls. The bicaudate index--the ratio of the width of both lateral ventricles at the level of the heads of the caudate nuclei to the distance between the outer tables of the skull at the same level--significantly discriminated among the three groups. The bicaudate indices were: Huntington disease 0.209 +/- 0.007, cerebral atrophy 0.121 +/- 0.006, and controls 0.092 +/- 0.003.     

Functional neuroimaging and presenting psychiatric features in frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a behavioural syndrome caused by degeneration of the frontal and anterior temporal lobes. Behavioural disturbances include psychiatric features. Whether patients with FTD present with psychiatric features varies with the initial neuroanatomical variability of FTD. OBJECTIVE: To identify presenting psychiatric changes not part of diagnostic criteria of FTD and contrast them with the degree of hemispheric asymmetry and frontal and temporal hypoperfusion on single photon emission computed tomography (SPECT) imaging. METHODS: 74 patients who met consensus criteria for FTD were evaluated at a two year follow up. All had brain SPECT on initial presentation. Results of an FTD psychiatric checklist were contrasted with ratings of regional hypoperfusion. RESULTS: The regions of predominant hypoperfusion did not correlate with differences on FTD demographic variables but were associated with presenting psychiatric features. Dysthymia and anxiety were associated with right temporal hypoperfusion. "Moria" or frivolous behaviour also occurred with temporal lobe changes, especially on the right. The only significant frontal lobe feature was the presence of a peculiar physical bearing in association with right frontal hypoperfusion. CONCLUSIONS: Patients with FTD may present with psychiatric changes distinct from the behavioural diagnostic criteria for this disorder. Early temporal involvement is associated with frivolous behaviour and right temporal involvement is associated with emotional disturbances. In contrast, those with right frontal disease may present with alterations in non-verbal behaviour.     

Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia

OBJECTIVES: Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. METHODS: The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. RESULTS: Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. CONCLUSIONS: Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the differential diagnosis of dementias.     

Review: Clinical,genetic and neuroimaging features of frontotemporal dementia

Frontotemporal dementia (FTD) is a heterogeneous group of disorders causing neurodegeneration within a network of areas centred on the frontal and temporal lobes. Clinically, patients present with behavioural symptoms (behavioural variant FTD) or language disturbance (primary progressive aphasia), although there is an overlap with motor neurone disease and atypical parkinsonian disorders. Whilst neuroimaging commonly reveals abnormalities in the frontal and temporal lobes, a closer review identifies a more complex picture with variable asymmetry of neuronal loss, widespread subcortical involvement and in many cases more posterior cortical atrophy. An autosomal‐dominant genetic disorder is found in around a third of people with mutations in progranulin, C9orf72 and the microtubule‐associated protein tau being the commonest causes. In the other two‐thirds, the disorder is sporadic, although recent genome‐wide association studies have started to identify genetic risk factors within this group. Much of this knowledge has been understood only in the past 10 years and so this review will discuss the current knowledge about the clinical, genetic and neuroimaging features of FTD.     

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.     

A volumetric magnetic resonance imaging study of the amygdala in frontotemporal lobar degeneration and Alzheimer's disease

The amygdala is severely atrophied at post-mortem in frontotemporal lobar degeneration (FTLD), and may contribute to the prominent behavioural changes that are early features of FTLD. The aim of this study was to assess amygdala atrophy using MRI in the main syndromic variants of FTLD and Alzheimer's disease (AD). Brain and amygdala volumes, adjusted for intracranial volume, were measured on 46 clinically diagnosed FTLD patients [22 frontal variant FTD (FTD), 14 semantic dementia (SD), 10 progressive non-fluent aphasia (PNFA)], 20 AD patients, and 17 controls. While severe amygdala atrophy was present in both FTLD (41% smaller than controls on the left; 33% on the right) and in AD (22% on the left; 19% on the right), the FTLD group had significantly greater amygdala atrophy (z = 3.21, p = 0.001 left, z = 2.50, p = 0.01 right) and left/right asymmetry (z = 2.03, p = 0.04) than AD. Amygdala atrophy was greater in SD than FTD, PNFA and AD (p < 0.02 for all). Highly asymmetrical atrophy was present in SD, greater on the left (z = 3.23, p = 0.001), and to a lesser extent in PNFA. Despite an overlap between clinical and radiological features of FTLD and AD, marked amygdala atrophy points towards a diagnosis of FTLD, with left greater than right atrophy suggestive of one of the language variants.