Biomedical subjects
Andrew Kertesz
Publications and source records attributed to Andrew Kertesz.
International approaches to frontotemporal dementia diagnosis: from social cognition to neuropsychology.
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The core and halo of primary progressive aphasia and semantic dementia.
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Frontotemporal degeneration, Pick's disease, Pick complex, and Ravel.
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Pick's complex and FTDP-17.
This essay advances the thesis with a review of the evidence that Pick's disease, frontotemporal dementia, primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy should be regarded as a clinically and biologically cohesive spectrum. The historically correct eponymic term Pick's complex, for both the clinical and pathological varieties is preferred. The discovery of tau mutations in frontotemporal dementia and parkinsonism linked to specific mutations in chromosome 17 and their resemblance to the sporadic cases validates the concept of Pick's complex. There are recently discovered overlaps between the three-repeat and four-repeat tauopathies, and the tau-negative varieties with or without motor neuron disease-type inclusions may be deficient in normal tau, therefore may be tauopathies also. Although clinical, pathological, and biochemical distinctions continue to be important, integration promises to be productive in this family of not so rare diseases.
Memantine in moderate to severe Alzheimer's disease.
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The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.
BACKGROUND: The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI. METHODS: Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer's Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging. RESULTS: Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n = 322) by DSM-IV, 10.2% (n = 137) by HIS, 4.3% (n = 58) by ICD-10, 3.8% (n = 51) by ADTCC, and 3.6% (n = 48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia. CONCLUSIONS: Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer's disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.
Primary progressive aphasia: diagnosis, varieties, evolution.
A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, "pure motor" presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent-nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge.
Pick Complex: an integrative approach to frontotemporal dementia: primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy.
BACKGROUND: Frontotemporal dementia (FTD) is a new label for clinical Pick's disease (PiD) because the eponymic term is increasingly restricted to the pathologic finding of Pick bodies. This restriction created the impression that PiD is rare and that is it difficult to diagnose. FTD is also a term most often used for behavioral and personality alterations. Primary progressive aphasia (PPA) and corticobasal degeneration (CBD), formerly the extrapyramidal variety of PiD, are also part of the syndrome. Recently, chromosome 17 localization and tau mutations were discovered in familial forms of the disease. REVIEW SUMMARY: FTD consists of behavioral and personality changes, often beginning with apathy and disinterest, which may be mistaken for depression. Disinhibition and perseverative, compulsive behavior often appear at the same time. A quantifiable frontal behavioral inventory is useful in the diagnosis beyond a checklist. The second type of presentation is progressive language loss (PPA). A less common variety is semantic dementia: the meaning of nouns and objects is lost. As the disease progresses, all components tend to overlap. CBD and progressive supranuclear palsy (PSP), although described as distinct entities, show a great deal of clinical, pathologic, genetic, and biochemical overlap. The evidence suggests they also belong to the complex. The association of motor neuron disease (MND) with FTD and other varieties of the complex is also reviewed. CONCLUSIONS: Clinical Pick's disease or Pick Complex includes the overlapping syndromes of FTD, PPA, CBD, PSP, and FTD-MND. The neuropathological and genetic spectrum should be viewed with emphasis on the commonalities rather than the differences, allowing the recognition of the relatively high frequency of this presenile syndrome.
Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomized trial.
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Frontotemporal dementia.
Frontotemporal dementia is a new name for clinical Pick's disease; the eponymic term PiD has been increasingly restricted to the pathologic variant with Pick bodies. This article describes the clinical picture, pathology, and genetic mechanisms of frontal lobe dementia. Frontotemporal dementia is still under-diagnosed and underestimated, partly because the individual components of the complex are considered separately or are considered "heterogeneous," a somewhat misleading adjective used in many descriptions. This article emphasizes the considerable overlap among the different varieties of frontotemporal dementia, as well as the distinctive features of each.
Behavioral quantitation is more sensitive than cognitive testing in frontotemporal dementia.
OBJECTIVE: To compare behavioral and cognitive testing in the clinical diagnosis of frontotemporal dementia (FTD). METHODS: A clinically defined cohort of FTD (n = 52) is compared with 52 Alzheimer disease (AD) patients on a Frontal Behavioral Inventory (FBI) and cognitive tests (e.g., Mini-Mental State Examination, Mattis Dementia Rating Scale, Western Aphasia Battery, Wechsler Intelligence Scale, Wechsler Memory Scale). Fourteen patients with FTD had autopsy confirmation, and their tests are also compared with the rest of the FTD population. RESULTS: The FTD and AD groups were matched in sex, duration, and severity of dementia. The total scores on the FBI showed the largest difference. Mini-Mental State Examination and Mattis Dementia Rating Scale total scores did not discriminate between the two groups. Memory subscores were lower in the AD group, and conceptualization and language-related scores were worse in the FTD group. Milder and earlier affected patients, who could carry on a large battery of neuropsychological tests, were much better distinguished by the FBI scores on discriminant function analysis. In contrast to 78% by the cognitive tests, 98% of the FTD and AD patients were differentiated by the FBI. CONCLUSIONS: Although memory scores were lower in AD and language scores in the FTD population, many of the cognitive tests do not distinguish between FTD and AD. On the other hand, a behavioral inventory is a useful adjunct in the diagnosis of FTD. Postmortem validation was carried out in a sizeable subset of the population, showing similar behavioral and cognitive data.
Frontotemporal dementia: one disease, or many?: probably one, possibly two.
Accumulating evidence suggest that frontotemporal dementia is best viewed as a clinical syndrome even though there are distinct presentations of the behavioral variety, progressive aphasia, semantic dementia, corticobasal degeneration and progressive supranuclear palsy. Similarly the pathology should be regarded as a spectrum even though histological varieties are distinguished. More than half of FTD pathology is associated with ubiquitin positive and tau negative inclusions that are common in ALS. However the majority of FTD cases do not have ALS clinically and relatively few ALS cases develop FTD. The pathological and biochemical varieties can be dichotomized as tau positive and tau negative pathology and biochemistry. The genetics of the tau positive variety is associated with tau mutations and so far the tau negative variety is not, although some are linked to chromosome-17 also. There is a corresponding clinical dichotomy combining the behavioral variety of FTD presentation with semantic dementia and usually ubiquitin positive tau negative pathology on one hand and the association of primary progressive aphasia and cortical basal degeneration/PSP syndrome with tau positive pathology on the other. The overlap between them is too great to establish two separate diseases.
Primary progressive aphasia: a review of the neurobiology of a common presentation of Pick complex.
Primary progressive aphasia (PPA) is an identifiable and distinct form of clinical presentation of focal degenerative disease. The underlying pathology is often considered heterogeneous, but we propose that, in fact, this syndrome has a characteristic underlying neurobiology related to Pick's disease and frontotemporal dementia. The authors reviewed the literature of PPA andfound 58 cases with autopsy. The majority of the cases had related underlying pathology, termed "Pick complex," a form of non-Alzheimer's dementia. This includes Pick's disease, corticobasal degeneration, dementia lacking distinctive histology, and motor neuron disease inclusions. Several of the cases described with focal Alzheimer's pathology do not fulfill the criteria of PPA, but have Alzheimer's disease with a major aphasic component.