The relationship between motor neurone disease (MND) and frontotemporal dementia (FTD) has been a topic of scientific exploration for over hundred years. A connection between both diseases was first postulated in 1932 and has been strengthened by a steady stream of case reports since then. By the late 20th century, the link between both diseases was firmly established, with the resulting condition often referred to as MND/FTD. Several strands of evidence support the notion of an MND/FTD overlap. First, a small but well-documented group of patients present with a full-blown FTD, associated with MND. Second, subtle but characteristic changes in frontal-executive functions and social cognition have been described in non-demented MND patients, often in association with frontal atrophy/hypoactivity on neuroimaging. Third, amyotrophic features have been documented in patients primarily diagnosed with FTD. Moreover, the same genetic defect can lead to FTD and MND phenotypes in different members of the same family. However, as the current research is moving toward a more fine-grained evaluation, an increasingly complex picture begins to emerge. Some features, such as psychotic symptoms or severe language deficits (particularly in comprehension and verb processing), seem to occur more often in MND/dementia than in the classical FTD. On the basis of the review of 100 years of literature as well as 10 years of clinical experience of longitudinal follow-up of MND/dementia patients, this review argues in favor of MND/dementia (or, more precisely, MND/dementia/aphasia) as a separate clinical entity, not sufficiently explained by a combination of MND and FTD.

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Dementia and depression are mental health problems that are commonly encountered in neuropsychiatric practice in the elderly. Approximately, half of the patients with late-onset depression have cognitive impairment. The prevalence of depression in dementias has been reported to be between 9 and 68%. Depression has been both proposed to be a risk factor for dementia as well as a prodrome of dementia. This article is a selective literature review of the complex relationship between the two conditions covering definitions, epidemiology, related concepts, treatment, and emerging biomarkers. The methodological issues and the mechanisms underlying the relationship are also highlighted. The relationship between the two disorders is far from conclusive.

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Frontotemporal dementia (FTD) syndromes comprise a heterogeneous group of neurodegenerative conditions characterized by atrophy in the frontal and temporal lobes. Three main clinical variants are recognized: Behavioral variant (bv-FTD), Semantic dementia (SD), and Progressive nonfluent aphasia (PNFA). However, logopenic/phonological (LPA) variant has been recently described, showing a distinctive pattern of brain atrophy and often associated to Alzheimer's disease pathology. The diagnosis of FTD is challenging, since there is clinical, pathological, and genetic overlap between the variants and other neurodegenerative diseases, such as motoneuron disease (MND) and corticobasal degeneration (CBD). In addition, patients with gene mutations (tau and progranulin) display an inconsistent clinical phenotype and the correspondence between the clinical variant and its pathology is unpredictable. New cognitive tests based on social cognition and emotional recognition together with advances in molecular pathology and genetics have contributed to an improved understanding. There is now a real possibility of accurate biomarkers for early diagnosis. The present review concentrates on new insights and debates in FTD.

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Background: Recent reports indicate that gait dysfunction can occur early in the course of cognitive decline suggesting that motor and cognitive functions in older adults may share common underlying brain substrates, pathological processes, and risk factors. Objective: This study was designed to report the association between gait and cognition in older adults in USA and the southern Indian state of Kerala. Materials and Methods: Literature review of gait and cognition studies conducted in Bronx County, USA as well as preliminary results from the Kerala-Einstein study (Kozhikode city, Kerala). Results: Review of published studies based in the Bronx shows that both clinical and quantitative gait dysfunction are common in older adults with cognitive impairment. Furthermore, clinical and quantitative gait dysfunction in cognitively normal older adults was a strong predictor of future cognitive decline and dementia. Our preliminary study in Kozhikode city shows that timed gait is slower in older adults diagnosed with dementia and mild cognitive impairment syndrome compared to healthy older controls. Conclusions: A strong association between gait and cognition is seen in seniors in USA as well as Kerala. A better understanding of the relationship between gait and cognition may help improve current diagnostic and therapeutic approaches globally.

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Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

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Frontotemporal lobar degeneration (FTLD) is a highly heterogenous group of progressive neurodegenerative disorders characterized by atrophy of prefrontal and anterior temporal cortices. Recently, the research in the field of FTLD has gained increased attention due to the clinical, neuropathological, and genetic heterogeneity and has increased our understanding of the disease pathogenesis. FTLD is a genetically complex disorder. It has a strong genetic basis and 50% of patients show a positive family history for FTLD. Linkage studies have revealed seven chromosomal loci and a number of genes including MAPT, PGRN, VCP, and CHMB-2B are associated with the disease. Neuropathologically, FTLD is classified into tauopathies and ubiquitinopathies. The vast majority of FTLD cases are characterized by pathological accumulation of tau or TDP-43 positive inclusions, each as an outcome of mutations in MAPT or PGRN, respectively. Identification of novel proteins involved in the pathophysiology of the disease, such as progranulin and TDP-43, may prove to be excellent biomarkers of disease progression and thereby lead to the development of better therapeutic options through pharmacogenomics. However, much more dissections into the causative pathways are needed to get a full picture of the etiology. Over the past decade, advances in research on the genetics of FTLD have revealed many pathogenic mutations leading to different clinical manifestations of the disease. This review discusses the current concepts and recent advances in our understanding of the genetics of FTLD.

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One of the first steps toward the correct diagnosis of dementia is to segregate out the nondegenerative dementias from possible degenerative dementias. Nondegenerative dementias could be due to traumatic, endocrine, metabolic, nutritional, toxic, infective, and immunological causes. They could also be caused by tumors, subdural hematomas, and normal pressure hydrocephalus. Many of the nondegenerative dementias occur at an earlier age and often progress quickly compared to Alzheimer's disease and other degenerative dementias. Many are treatable or preventable with simple measures. This review aims to give an overview of some of the more important endocrine, metabolic, nutritional, and toxic disorders that may lead to dementia.

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Primary progressive aphasia (PPA) is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca's area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face) meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick's disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon) increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.

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Alzheimer's disease (AD) is the commonest progressive, dementing neurodegenerative disease in elderly, which affects innumerable people each year, and these numbers are likely to further increase as the population ages. In addition to the financial burden of AD on health care system, the disease has powerful emotional impact on caregivers and families of those afflicted. In this advancing era of AD research, with the availability of new treatment strategies having disease-modifying effects, there is growing need for the early diagnosis in AD, often hampered by paucity of biomarkers of AD. Various candidate biomarkers for AD have been developed that can detect patients with AD at an early stage. In the recent years, the search for an ideal biomarker has undergone a rapid evolution. Novel technologies in proteomics, genomics, and imaging techniques further expand the role of a biomarker not only in early diagnosis, but also in monitoring the response to various treatments. However, the availability of sensitive and specific biomarkers requires the method to be standardized so as to be able to compare the results across studies. Inspite of tremendous advances in this field the quest for an "ideal biomarker" still continues. In this review, we will discuss the various candidate markers in five spheres namely biochemical, neuroanatomical, metabolic, genetic and neuropsychological, and their current status and limitations in AD diagnosis.

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The behavioral and psychological symptoms of dementia (BPSD) have been a difficult management area for neurologists and psychiatrists alike. The correct identification of each symptom and the underlying precipitating cause is the key to proper management-nonpharmacological as well as pharmacological. BPSD has been well documented in all types of dementia in various stages of the disease and in all dementias at an advanced stage. The proper management is not only rewarding in terms of responsiveness in an otherwise "incurable" and progressive disease, but also improves the quality of life of the patients and the caregivers alike. The caregiver burden is greatly decreased by an efficient management of BPSD. This review discusses the implications and boundaries of the term BPSD and unravels each symptom and its identification. Manifestations of psychological symptoms such as delusion, hallucination, misidentification, psychosis, depression, apathy, and anxiety are briefly described. Correct identification of behavior symptoms such as wandering, agitation, catastrophic reaction, disinhibition, and delirium has been outlined. While the subtle differences in each entity make the precise identification difficult, the different therapeutics of each make the exercise necessary. Pharmacological recommendations and side effects of medications have been mentioned thereafter. The review will help in the identification and correct pharmacological management of BPSD.

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Cognitive impairment due to cerebrovascular disease is termed "Vascular Cognitive Impairment" (VCI) and forms a spectrum that includes Vascular Dementia (VaD) and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment (VaMCI). VCI represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors such as hypertension, diabetes, obesity, dyslipidemia, and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Mixed degenerative and vascular pathologies are increasingly being recognised and an interaction between the AD pathology, vascular risk factors, and strokes is now proposed. The high cardiovascular disease burden in India, increasing stroke incidence, and ageing population have contributed to large numbers of patients with VCI in India. Inadequate resources coupled with low awareness make it a problem that needs urgent attention, it is important identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia.

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