PubMed Health⌕ Search

Biomedical subjects

M Nadeem Khan

Publications and source records attributed to M Nadeem Khan.

6 recordsLinked to original sources
PubMed2005

Sporadic and familial dementia with ubiquitin-positive tau-negative inclusions: clinical features of one histopathological abnormality underlying frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration comprises a group of diseases with clinical presentations and underlying histopathologies that overlap. Familial disease occurs in up to 50% of frontotemporal lobar degeneration cases. One of several underlying histopathological abnormalities is of ubiquitin-positive tau-negative inclusions, similar to those in motor neuron disease. OBJECTIVE: To compare clinical features of familial and sporadic cases in this pathological subgroup. DESIGN AND PATIENTS: Case note review of dementia patients with ubiquitin-positive tau-negative inclusion pathological abnormalities proven by autopsy. SETTING: United Kingdom tertiary referral center. MAIN OUTCOME MEASURES: Analysis of clinical features. RESULTS: Eleven familial cases (autosomal dominant) and 18 sporadic cases were identified. Most familial case patients presented with behavioral disturbances similar to those seen in sporadic behavioral cases. Semantic dementia was only seen in sporadic cases. Atypical features occurred in a minority. Sporadic and familial behavioral cases showed no differences in age at onset or disease duration. Neuropsychological test results revealed frontal or temporal deficits in most, but unexpected early parietal deficits in 1. CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases.

Age of Onset↗
PubMed2005

Rate of progression of cognitive decline in Alzheimer's disease: effect of butyrylcholinesterase K gene variation.

OBJECTIVE: To determine whether individuals with Alzheimer's disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase. METHOD: The cognitive status of 339 community based subjects with AD was assessed with the Mini Mental State Examination at baseline and yearly over a three year follow up period. The rates of cognitive decline of subjects with and without the K variant allele were compared. RESULT: Presence of the K allele was associated with a slower average rate of cognitive decline in subjects with severe AD. CONCLUSIONS: This finding is consistent with the suggestion that the K variant of butyrylcholinesterase has an important role in disease progression in AD, and this may have implications for treatment.

Aged↗
PubMed2004

Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation.

The neuronal ceroid-lipofuscinoses (NCLs) are recessively inherited lysosomal storage diseases, currently classified into 8 forms (CLN1-CLN8). Collectively, the NCLs constitute the most common group of progressive encephalopathies of childhood, and present with visual impairment, psychomotor deterioration and severe seizures. Despite recent identification of the underlying disease genes, the mechanisms leading to neurodegeneration and epilepsy in the NCLs remain poorly understood. To investigate these events, we examined the patterns of storage deposition, neurodegeneration, and glial activation in the hippocampus of patients with CLN1, CLN2, CLN3, CLN5 and CLN8 using histochemistry and immunohistochemistry. These different forms of NCL shared distinct patterns of neuronal degeneration in the hippocampus, with heavy involvement of sectors CA2-CA4 but relative sparing of CA1. This selective pattern of degeneration was also observed in immunohistochemically identified interneurons, which exhibited a graded severity of loss according to phenotype, with calretinin-positive interneurons relatively spared. Furthermore, glial activation was also regionally specific, with microglial activation most pronounced in areas of greatest neuronal loss, and astrocyte activation prominent in areas where neuronal loss was less evident. In conclusion, the NCLs share a common pattern of selective hippocampal pathology, distinct from that seen in the majority of temporal lobe epilepsies.

Adolescent↗
PubMed2004

Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies.

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies. CONCLUSIONS: The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.

Aged↗
PubMed2003

Olfactory bulb in multiple system atrophy.

Olfactory dysfunction is a characteristic clinical sign in Parkinson's disease (PD); it is also present in multiple system atrophy (MSA). The pathological basis of hyposmia or anosmia in PD is well known: the olfactory bulb (OB) contains numerous Lewy bodies and severe neuronal loss is present in the anterior olfactory nucleus (AON). We established that glial cytoplasmic inclusions (GCIs) are present in all the OBs from MSA cases. Their presence in the OB is diagnostic for MSA. Additionally, neuronal loss is present in the AON in MSA. These pathological changes might be responsible for the olfactory dysfunction seen in MSA.

Aged↗