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Several genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks. An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes.

Late-onset Alzheimer disease (LOAD) is a common disorder with a substantial genetic component. We postulate that many disease susceptibility variants act by altering gene expression levels.

Recently, mutations in DCTN1were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1in neurodegeneration.

Measurement of volumetric changes with MR might be a useful surrogate endpoint for clinical trials in frontotemporal lobar degeneration (FTLD). Because there is only limited longitudinal imaging data currently available, we measured the rate of change over 1 year of whole brain volume (WBV) and ventricular volume (VV) in patients with FTLD.

Plasma A levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD).

The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD).

To compare logistic and bilogistic models to describe the pattern of cognitive decline in the preclinical phase of Alzheimer disease (AD).

To compare survival and rates of cognitive and functional decline in patients with autopsy-confirmed frontotemporal dementia (FTD) and Alzheimer disease (AD) in a large multicenter study.

To examine the clinical, genetic, and neuropathologic features of posterior cortical atrophy (PCA).

To determine whether certain aspects of fluctuations reliably distinguish dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and normal aging.

To determine, in a cross-sectional evaluation of nondemented individuals, if age-related memory decline is influenced by apolipoprotein E (apoE) genotype.

Early reports suggested that corticobasal degeneration (CBD) is a distinct clinicopathologic entity. Because patients have had a fairly consistent constellation of clinical and laboratory findings, many have proposed that the pathologic diagnosis can be surmised with confidence during life.

The role of individual structures within the diencephalon for memory functioning is unknown. We present anatomic localization of lesions and a longitudinal neuropsychological profile of a young man who had a bilateral diencephalic stroke in the interpeduncular profundus arterial territory. MRI localized the lesions to the mamillothalamic tracts and inferior thalamic peduncle. The amnesia was characterized by severe impairment in explicit recall of new facts and events, while word-completion priming and remote memory were intact. We suggest that the memory deficit results from a disconnection of the diencephalon from the medial temporal region.

Although Pick's disease is generally considered as a dementia characterized by signs of frontal lobe dysfunction, it can present with selective language defects rather than with cognitive decline. In this study, we report prospective and serial clinical, neuropsychological, and neuroradiologic observations in a 59-year-old man whose prominent disturbance was in the retrieval and learning of names denoting concrete entities and actions. Postmortem study confirmed the diagnosis of Pick's disease and revealed that neuronal loss and gliosis were most prominent in left anterior temporal cortices. The findings are in keeping with evidence that the left anterior temporal cortices and interconnected hippocampal System are critically involved in the learning and retrieval of verbal lexical items. The evidence from this patient, along with similar evidence from the literature we reviewed, suggests that when patients present with a progressive aphasia characterized by anomia, Pick's disease should be considered as the probable diagnosis.

A 39-year-old right-handed woman suffered a ruptured pericallosal aneurysm. Serial MRI studies showed damage to the genu and most of the body of the corpus callosum but not the splenium. Both supplementary motor areas (SMA) appeared intact. We studied the patient's praxis performance at intervals over a 4-month period with a standardized battery. The study suggests that apraxia seen in patients with callosal lesions is probably due to the callosal damage, not to the usually associated SMA lesion. Our findings support Liepmann's idea that the left hemisphere is dominant for praxis in both hands. We propose, however, that the dominance effect is related to the type of test given and varies among individuals. As regards the latter, in some individuals the left hemisphere is strongly dominant for motor tasks, while in others it is less so. As regards the type of test, the most enduring left-hand apraxia is seen in verbal, not visuomotor tests.

A significant correlation between brain atrophy and impairment on neuropsychological testing in young alcoholics was found. Chronological age also correlated with brain atrophy, supporting the hypothesis that excessive drinking causes premature aging of the brain.

We studied the effects of medial pallidotomy in the first 20 consecutive patients with Parkinson's disease (PD) undergoing this MRI/electrophysiologically guided procedure at our institution. The mean age of patients was 65.5 years (median 66.5) and none suffered any serious complications. Pallidotomy significantly improved motor function in both "on" and "off" states as measured by United Parkinson's Disease Rating Scale(UPDRS) motor scores and timed tests (Purdue pegboard and counter tapping) in the arm contralateral to surgery 3 months postoperatively. Patients also improved in terms of activities of daily living, reflected by improved UPDRS activity of daily living and complications of therapy scoring and reduced levodopa-induced dyskinesias; six of 11 patients who could not walk in an "off" state prior to surgery could do so postoperatively. The total UPDRS score improved by 22% from preoperative values. The aforementioned improvements occurred similarly in patients greater than (n = 11) or less than 65 years (n = 9) at surgery. Neuropsychological measures indicated that although the majority of cognitive function remains unchanged in right-handed PD patients following dominant (left) hemisphere pallidotomy, mild specific declines in word generation are present. The findings of this study suggest that unilateral pallidotomy is safe and associated with improved motor functioning in elderly as well as younger PD patients experiencing significant disability despite optimal medical therapy.

Genetic factors are important in Alzheimer disease (AD) and Parkinson disease but have not been well characterized in Lewy body dementia (LBD). The authors obtained family history in patients from an autopsy series of AD and LBD and in living healthy controls. A family history of dementia was more common in both LBD and AD compared with controls, suggesting that genetic factors are as important in LBD as they are in AD.