Clinicopathological co-occurrence of Fahr's disease and dementia with Lewy bodies.

We present the clinicopathological findings of a case of combined Fahr's disease (FD) and dementia with Lewy bodies (DLB), associated with a novel pathogenic mutation. The patient presented with visual hallucinations, fluctuating confusion and parkinsonism, leading to a presumptive diagnosis of DLB. CT scan showed extensive bilateral parenchymal calcifications, suggestive of FD. DNA sequencing identified a novel missense variant (c.92A>T p.(Asn31Ile)) in the SLC20A2 gene, a gene known to be associated with FD. This change has not been previously recorded in genetic repositories, and in silico analyses classified it as likely to be disease-causing. The patient died aged 77, four years after symptom onset. Neuropathological examination revealed, macroscopically and microscopically, extensive calcification in the striatum, globus and cerebellar white matter. There was also neuronal loss in the substantia nigra and residual neurones contained alpha-synuclein-positive Lewy bodies. The neuropathology was therefore consistent with DLB and FD. A literature review identified 3 other cases of co-existing Fahr's and Lewy body pathology, thus the frequency of dual pathology (44%) is higher than expected by random association. Further studies are needed to determine whether alpha-synucleinopathy is linked mechanistically to FD and/or represents a phenotypic subtype.

A comparison of the Addenbrooke's Cognitive Examination (ACE), conventional neuropsychological assessment, and simple MRI-based medial temporal lobe evaluation in the early diagnosis of Alzheimer's disease.

OBJECTIVE: To examine the contribution of the Addenbrooke's Cognitive Examination (ACE), neuropsychological assessment, and a magnetic resonance imaging (MRI)-based temporal lobe rating scale to the prediction of which patients with questionable dementia will progress to Alzheimer's disease (AD). METHODS: Fifty subjects (19 early AD, 31 questionable dementia [QD]) underwent the ACE, a neuropsychological evaluation, and a volumetric MRI. The degree of atrophy of hippocampal, parahippocampal, and other temporal lobe structures was assessed using a validated visual rating scale. Subjects were followed 8 monthly for an average of 19.1 months. RESULTS: Of the 31 QD subjects, 11 converted to AD within 24 months of follow-up (another 2 developed dementia with Lewy bodies) and 18 were nonconverters. Converters were impaired relative to nonconverters at baseline on measures of episodic and semantic memory (category fluency and naming) and the ACE. Converters also had a greater degree of hippocampal and parahippocampal atrophy. Discriminant analysis demonstrated that the best single test for distinguishing converters was the ACE. In combination, the hippocampal rating and category fluency were also contributory. CONCLUSIONS: Progression to AD in patients with QD is best predicted by neuropsychological measures, particularly those that assess episodic and semantic memory, although simple rating methods based on MRI may have an adjunctive role.

Recollection-based memory in frontotemporal dementia: implications for theories of long-term memory.

It has been convincingly demonstrated that patients with semantic dementia (the temporal variant of frontotemporal dementia) can show intact recognition memory for pictorial stimuli. As yet, the contribution made by recollective processes to this ability and the status of associated neural regions have not been investigated in the disease. Here, we used both a source monitoring paradigm and an associative memory test to evaluate the ability of patients with semantic dementia to use recollection-based memory processes, and a volumetric MRI technique to assess the extent of atrophy in the hippocampus. Although some patients showed impaired source and associative memory, many performed as well as control participants. Importantly, status of semantic knowledge, as measured by tests of comprehension and production, did not predict recollection-based memory ability. There was no significant positive correlation between recollection and volume of the hippocampus; instead, both source discrimination and associative memory correlated highly with performance on a battery of frontal lobe tests. Consistent with the view that damage to the prefrontal cortex might influence recollection performance, patients with the frontal variant of frontotemporal dementia, with atrophy largely confined to the frontal lobes, all performed at floor level on source discrimination. These results provide further compelling evidence in favour of the multiple input model of long-term memory and highlight the role of frontal lobe systems in recollection-based memory.