P. S. Mathuranath

A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia

Objectives: To validate a simple bedside test battery designed to detect mild dementia and differentiate AD from frontotemporal dementia (FTD). Methods: Addenbrookes Cognitive Examination (ACE) is a 100-point test battery that assesses six cognitive domains. Of 210 new patients attending a memory clinic, 139 fulfilled inclusion criteria and comprised dementia (n = 115) and nondementia (n = 24) groups. The composite and the component scores on the ACE for the two groups were compared with those of 127 age- and education-matched controls. Norms and the probability of diagnosing dementia at different prevalence rates were calculated. To evaluate the ACEs ability to differentiate early AD from FTD, scores of the cases diagnosed with dementia with a Clinical Dementia Rating < 1 (AD = 56, FTD = 24, others = 20) were compared. Results: Two cut-off values for the ACE composite score (88 and 83) were of optimal utility depending on the target population. The ACE had high reliability, construct validity, and sensitivity (93%, using 88 as cut-off). Using the lower cut-off of 83, the ACE had a higher sensitivity (82%) and predictive value than the Mini-Mental State Examination for a wide range of dementia prevalence. The ACE differentiated AD from FTD, and the VLOM ratio (derived using component scores: [verbal fluency + language]/[orientation + memory]) of <2.2 for FTD and >3.2 for AD was highly discriminating. Conclusion: The ACE is a brief and reliable bedside instrument for early detection of dementia, and offers a simple objective index to differentiate AD and FTD in mildly demented patients.

Subcortical dementia revisited: Similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA)

To examine the similarities and differences in cognitive function between three predominantly subcortical dementing disorders associated with parkinsonism we compared the profiles of cognitive performance in 39 patients with Progressive Supranuclear Palsy (PSP), 26 patients with Multiple System Atrophy (MSA) and 25 with Corticobasal Degeneration (CBD) with those of 30 patients with classic cortical dementia, Alzheimer’s Disease (AD), using two different cognitive screening tests: Dementia Rating Scale (DRS) and Addenbrooke’s Cognitive Examination (ACE). The cognitive profile on ACE and DRS subtests distinguished subcortical diseases from each other as well as from AD. All parkinsonian syndromes were characterized by a disproportionate impairment in verbal fluency, particularly letter fluency. The three diseases differed, however, in the degree of language, memory and visuospatial impairment. We conclude that similarities, as well as differences, between PSP, MSA and CBD can be detected using a brief, clinically applicable cognitive screening test. The pattern of cognitive impairment is likely to reflect a different distribution of pathology, in particular a higher degree of cortical involvement in PSP and CBD. We would like to thank Marion Wilkinson and Ashley Muir for their help in preparation of the manuscript, Joanna Drake and Tina Emery for their assistance in testing patients and controls and Sharon Davies for her assistance in data management. Our work on PSP and CBD patients has been generously supported by the PSP Association, our work on MSA patients by Sarah Mathieson Trust.

Effects of Age, Education and Gender on Verbal Fluency

The objective was to study the effects of age, education and gender on verbal fluency in cognitively unimpaired, older individuals. The methods used were as follows: cognitively unimpaired elderly (55-84 years) subjects (n = 153), were administered category (animal) (CF) and letter (/pa/) (LF) fluency tasks, in their native language of Malayalam. Results and conclusions were (1) Level of education, but not age or gender, significantly influence LF. (2) Level of education (directly) and in the elderly subjects, age (inversely) affect CF. (3) Age, but not education, has a differential effect on the tasks of verbal fluency, influencing CF more than LF.

Corticobasal ganglionic degeneration and/or frontotemporal dementia? A report of two overlap cases and review of literature

OBJECTIVE According to the existing viewpoint, Corticobasal degeneration (CBD) is thought of as a predominantly extrapyramidal motor disorder that is distinct and unrelated to frontotemporal dementia (FTD), the most common form of non-Alzheimer dementias. A lack of understanding of the aetiopathogenesis, and poor correlation between the pathology and the clinical syndromes, has resulted in a disparity in the classification of cases of non-Alzheimer dementias. This report intends to highlight the overlap between FTD and CBD in the light of the evolution of these terms, and to discuss the implications of these findings on the nosology of CBD and the classification of non-Alzheimer dementias. METHODS AND RESULTS Two cases who presented with cognitive dysfunction, which, on comprehensive neuropsychological testing warranted an antemortem diagnosis of FTD are reported. A detailed necropsy study of their brains, however, favoured a pathological diagnosis of CBD. The literature on the overlap between CBD and FTD is also reviewed. CONCLUSIONS Firstly, evidence is emerging to suggest that the clear distinction drawn between FTD and CBD by the existing viewpoint, needs revision. Secondly, until such time that a comprehensive classification of non-Alzheimer dementias is evolved, it may be better to distinguish between the clinical and pathological levels of description and to classify cases, in vivo, on the basis of the clinical phenotype.

Cognitive bedside assessment in atypical parkinsonian syndromes

Background: Despite the growing recognition of the importance of cognitive symptoms for the diagnosis and management of atypical parkinsonian syndromes, the cognitive assessment of the patients in clinical practice often remains very limited. Objectives: To examine the ability of a brief and simple cognitive screening test to detect cognitive deficits in atypical parkinsonian syndromes. Methods: Addenbrooke’s cognitive examination (ACE), the mini-mental state examination (MMSE), and the dementia rating scale (DRS) were applied to 26 patients with multiple system atrophy (MSA), 39 with progressive supranuclear palsy (PSP), and 25 with corticobasal degeneration (CBD). The results were then compared with those obtained in 30 healthy age matched volunteers and 30 patients with Alzheimer’s disease. Results: In all four diseases the rate of detection of cognitive impairment on ACE was higher than on MMSE and comparable with DRS. The severity of cognitive impairment was most pronounced in the CBD group, which showed a similar degree of impairment to the Alzheimer group. In contrast, MSA patients were the least cognitively impaired. The PSP group took an intermediate position. Conclusions: Cognitive impairment in atypical parkinsonian syndromes can be detected using a brief and clinically applicable bedside test such as ACE.

Mini Mental State Examination and the Addenbrooke's Cognitive Examination: Effect of education and norms for a multicultural population

OBJECTIVE To derive population norms on the Malayalam adaptation of Addenbrookes Cognitive Examination (M-ACE) and the inclusive Malayalam mini mental state examination (M-MMSE). MATERIALS AND METHODS Education-stratified norms were obtained on randomly selected cognitively unimpaired community elders (n = 519). RESULTS Valid data on norms was available on 488 subjects (age 68.5 +/- 7.1 and education 7.9 +/- 5.4). Education and age, but not gender had a significant effect on both M-ACE and M-MMSE. When compared to the effect of age, the effect of education was sevenfold more on the M-ACE and ninefold more on the M-MMSE. The mean composite score on the M-ACE (and the M-MMSE) was 42.8 +/- 9.8 (14.9 +/- 3.1) for those with 0 (n = 72), 55.9 +/- 12.5 (19.7 +/- 4.1) with 1-4 (n = 96), 62.6 +/- 11.4 (21.9 +/- 3.7) with 5-8 (n = 81), 77 +/- 10.2 (25.7 +/- 2.4) with 9-12 (n = 136) and 83.4 +/- 7.2 (26.7 +/- 1.6) with > 12 (n = 103) years of formal education. CONCLUSIONS Education has the most potent effect on performance on both M-ACE and M-MMSE in the Indian cohort. Education-stratified scores on the M-ACE and the M-MMSE, will provide a more appropriate means of establishing the cognitive status of patients. It is also our feeling that these cut-off scores will be useful across India.

Instrumental activities of daily living scale for dementia screening in elderly people

OBJECTIVE To develop and validate an Instrumental Activities of Daily Living Scale for elderly people (IADL-E) to use in conjunction with cognitive screening tests for dementia in an educationally and socioculturally heterogeneous population. METHOD Eleven IADL items were selected and weighted for major factors causing heterogeneity in the population--gender, education, social (rural/urban) setting and age. Each item was rated for its applicability (yes/no), degree of disability (scored from 0 to 2) and causative impairment (cognitive and/or physical). From this a composite index of cognitive (CDI) or physical (PDI) disability was derived. Validation was performed retrospectively on 240 subjects: 135 without and 105 with dementia by DSM-IV. RESULTS The IADL-E had a high internal consistency (alpha = 0.95). The area under the receiver operating characteristic (ROC) curve was 0.97 (CI = 0.94-0.99). A cutoff score of 16 on CDI provided a sensitivity of 0.91, specificity 0.99 and positive predictive value 0.76 (at 5% base rate). IADL-E correlated highly with clinical (DSM-IV, kappa = 0.89), functional (CDR, 0.82) and cognitive (Mini-mental Status Examination, MMSE, 0.74) diagnoses. It showed good responsiveness, with the change on CDI over a median of 23 months correlating significantly with that on MMSE (coefficient = -0.382, CI = -0.667 to -0.098; p=0.009). Individual items had good interrater and test-retest reliability. CONCLUSIONS The IADL-E is a reliable, sensitive and responsive scale of functional abilities useful in dementia screening in a socioculturally heterogeneous population.

Dementia in Kerala, South India: prevalence and influence of age, education and gender

Data on the prevalence of dementia in India with a large and aging population is scant. We studied prevalence of AD and dementia in Kerala, South India, and effects of age, education and gender on it.

Tau and Tauopathies

Tau protein is a neuronal microtubule-associated protein (MAP), which localizes primarily in the axon. It is one of the major and most widely distributed MAPs in the central nervous system. Its biochemistry and molecular pathology is being increasingly studied. Tau is a key component of neurofbrillary tangles in Alzheimers disease (AD). Disorders with neuronal, oligodendroglial or astrocytic filamentous tau inclusions are now grouped under the common rubric of tauopathies. The discovery of mutations in the tau gene, located on Chromosome 17 and its relationship to frontotemporal dementia with Parkinsonism (FTDP-17) has enhanced the importance of tau protein in cognitive neurology. Aberrant aggregates of tau have been documented in most of the neurodegenerative diseases with filamentous inclusions. The role of cerebrospinal fluid tau in the diagnosis of dementias is being investigated quite extensively. Recently, it has been shown that Abeta immunotherapy leads to the clearance of early tau pathology. It is becoming clearer that understanding tau better will lead to better understanding of many neurodegenerative diseases that may help develop interventional strategies.

Picture-Based Memory Impairment Screen for Dementia

To develop and validate a picture‐based memory impairment screen (PMIS) for the detection of dementia.