Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy.

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression.

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients.

Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease.

Introduction: The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain.

Methods: We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study.

Results: We confirm that variation in/near APOE/TOMM40 (P = 6 × 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.

Neuropsychiatric Symptoms in Posterior Cortical Atrophy and Alzheimer Disease.

Background: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by early progressive visual dysfunction in the context of relative preservation of memory and a pattern of atrophy mainly involving the posterior cortex. The aim of the present study is to characterize the neuropsychiatric profile of PCA.

Methods: The Neuropsychiatric Inventory was used to assess 12 neuropsychiatric symptoms (NPS) in 28 patients with PCA and 34 patients with typical Alzheimer disease (AD) matched by age, disease duration, and illness severity.

Restoration of conceptual knowledge in a case of semantic dementia.

Patients with semantic dementia (SD) may undergo successful relearning of object names, but these gains are usually restricted to the trained exemplars, demonstrating poor generalization. We hypothesized that generalization could be improved by restoring an item's semantic network through specific strategies that recruit the remaining personal semantic memories (conceptual enrichment therapies). We describe the case of a patient with SD who showed greater generalization of learning following a conceptual enrichment therapy than when learning items in a word-retrieval therapy.

Utility of neuropsychiatric tools in the differential diagnosis of dementia with Lewy bodies and Alzheimer's disease: quantitative and qualitative findings.

Background: Discerning dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) is one of the most common and challenging differential diagnoses at the memory clinic. Although the neuropsychiatric manifestations have been widely reported as one of the main key points in the differential diagnosis between these two diseases, to date no neuropsychiatric questionnaire has been specifically devised for this purpose.

Methods: We administered the Neuropsychiatric Inventory (NPI) and the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD) to a memory clinic sample of 80 patients with probable DLB and 85 age- and severity-matched patients with probable AD.

Abnormal sensorimotor plasticity in CADASIL correlates with neuropsychological impairment.

Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene. CADASIL progresses, in some cases, to subcortical dementia with a particular cognitive impairment. Different diseases in the dementia spectrum share a central cholinergic and sensorimotor plasticity alteration.

C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration.

Objective: Expansions of more than 30 hexanucleotide repetitions in the C9ORF72 gene are a common cause of frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS). However, the range of 20-30 repetitions is rarely found and still has unclear significance. A screening of our cohort of cases with FTD (n = 109) revealed 4 mutation carriers (>30 repetitions) but also 5 probands with 20-22 confirmed repetitions.

Disturbed sleep patterns in elders with mild cognitive impairment: the role of memory decline and ApoE ε4 genotype.

Sleep disturbances are prevalent in patients with Alzheimer' disease (AD), being one of the most troubling symptoms during the progression of disease. However, little research has been made to determine if impaired sleep patterns appear years before AD diagnosis. This study tries to shed light on this issue by performing polysomnographic recordings in healthy elders and patients with mild cognitive impairment (MCI).

Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations.

We describe the clinical phenotype of nine kindred with presenile Alzheimer's disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare them with reported families with mutations in the same codons. Mutations were in exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7 (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser). Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not been previously reported.

Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer's disease.

Neuropathological studies suggest that the basal forebrain cholinergic system (BFCS) is affected in Alzheimer's disease (AD), but there is no in vivo evidence of early damage to this system in subjects at high risk of developing AD. Here, we found that mild cognitive impairment (MCI) patients exhibited significant volume reduction of the nucleus basalis of Meynert (NbM) using recently developed probabilistic maps of the BFCS space. In addition, volumes of different magnocellular compartments varied significantly with regional gray matter atrophy in regions known to be affected by AD and were found to correlate with cognitive decline in MCI patients.

Functional integrity of thalamocortical circuits differentiates normal aging from mild cognitive impairment.

Resonance in thalamocortical networks is critically involved in sculpting oscillatory behavior in large ensembles of neocortical cells. Neocortical oscillations provide critical information about the integrity of thalamocortical circuits and functional connectivity of cortical networks, which seem to be significantly disrupted by the neuronal death and synapse loss characterizing Alzheimer's disease (AD). By applying a novel analysis methodology to overcome volume conduction effects between scalp electroencephalographic (EEG) measurements, we were able to estimate the temporal activation of EEG-alpha sources in the thalamus and parieto-occipital regions of the cortex.

Increased synchronization and decreased neural complexity underlie thalamocortical oscillatory dynamics in mild cognitive impairment.

Abnormal patterns of electroencephalographic (EEG) alpha oscillations in preclinical stages of dementia reveal a selective vulnerability of thalamocortical circuits to the cascade of neurodegenerative events heralding Alzheimer's disease (AD). EEG-alpha slowing characterizes both mild cognitive impairment (MCI) and healthy aging, but it remains ambiguous whether different neural mechanisms underlie this oscillatory behavior in normal and pathological senescence. In this study, we show that the strength of phase coupling and the level of phase predictability between thalamocortical and cortico-cortical EEG sources of low alpha frequency are abnormally facilitated in MCI patients when compared to healthy elderly subjects.

Relationship between the efficacy of rivastigmine and apolipoprotein E (epsilon4) in patients with mild to moderately severe Alzheimer disease.

Alzheimer disease is the most common form of dementia in Western countries and the leading cause of disability in the over-65 population. Apolipoprotein E (APOE) is a multifunctional protein implied in lipid metabolism and neurobiology. Polymorphisms of the APOE gene have been associated with a variety of medical disorders, from arteriosclerosis to AD.

Left hemicranial hypoplasia in 2 patients with primary progressive aphasia.

Background: Primary progressive aphasia (PPA) leads to a gradual and relatively isolated dissolution of language function. The factors that determine the selectivity of the disease process remain unknown. We had speculated that PPA may occasionally arise as a tardive manifestation of genetic or acquired vulnerabilities involving the language network of the brain.

Mitochondrial DNA A4336G mutation in Alzheimer's and Parkinson's diseases.

Objectives: To determine whether the mitochondrial DNA (mtDNA) A4336G mutation represents a risk factor for Spanish patients with both Alzheimer's disease (AD) and Parkinson's disease (PD).

Material And Methods: One hundred and sixty-one AD and 106 PD unrelated patients were included in the study. Seventy-eight age-matched and 144 randomly chosen healthy subjects served as controls.