Dementia is a growing public health problem for which early detection may be beneficial. Currently, the diagnosis of dementia in primary care is dependent mostly on clinical suspicion based on patient symptomsor caregivers' concerns and is prone to be missed or delayed. We conducted a systematic review of the literature to ascertain the prevalence and contributing factors for missed and delayed dementia diagnoses in primary care. Prevalence of missed and delayed diagnosis was estimated by abstracting quantitative data from studies of diagnostic sensitivity among primary care providers. Possible predictors and contributory factors were determined from the text of quantitative and qualitative studies of patient-, caregiver-, provider-, and system-related barriers. Overall estimates of diagnostic sensitivity varied among studies and appeared to be in part a function of dementia severity, degree of patient impairment, dementia subtype, and frequency of patient-provider contact. Major contributory factors included problems with attitudes and patient-provider communication, educational deficits, and system resource constraints. The true prevalence of missed and delayed diagnoses of dementia is unknown but appears to be high. Until the case for dementia screening becomes more compelling, efforts to promote timely detection should focus on removing barriers to diagnosis.

These data confirm the presence of cognitive impairment in 50% of patients with ALS and particularly implicate executive dysfunction and mild memory decline in the disease process. More severe impairment occurs in a subset of patients with ALS and has features consistent with FTD.

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a potential cellular substrate underlying memory. It is important to determine the pre- and/or postsynaptic locus of LTP expression in order to study its underlying mechanisms. Despite intensive investigation, however, its locus of expression remains uncertain. It has been hypothesized that if LTP expression includes a presynaptic locus then it may alter the expression of another presynaptically mediated form of potentiation like paired-pulse facilitation (PPF), which is an increase in a second population excitatory postsynaptic potential when it is elicited shortly after a first. Previous authors have found no change in PPF in association with LTP. We re-examined the hypothesis, however, to reconcile the negative PPF data with other data that have suggested presynaptic involvement in LTP. Extracellular recordings were made in area CA1 of the rat hippocampal slice preparation. Surprisingly, PPF both increased and decreased significantly in association with LTP. The changes in PPF occurred in a predictable way, however. They correlated inversely with initial PPF magnitude so that a larger initial PPF was associated with a decrease in PPF with LTP while a smaller initial PPF was associated with an increase. Because PPF increased or decreased in individual slices in association with LTP, the average PPF of all slices did not change, in agreement with previous studies. The changes in PPF were also specific to LTP; that is, they were input specific, were not due to changes in inhibition or nonspecific effects of high- frequency stimulation, were not due to active postsynaptic currents or their nonlinear summation, and PPF changed with the same time course as LTP. We conclude that the mechanism of early LTP expression includes at least the presynaptic locus. Two hypotheses regarding the presynaptic mechanism underlying LTP expression, which are consistent with finding both increases and decreases in PPF with LTP, are (1) that there is an increase in the number of release sites with LTP or (2) that there is an increase in both the number of release sites and the probability of neurotransmitter release. Increases in the probability of neurotransmitter release alone would not appear to account for our findings since such increases have been associated only with decreases in PPF. Our findings do not exclude additional postsynaptic involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Up to half of patients with ALS develop cognitive impairment during the course of the illness. Despite this, there is no simple tool for screening patients in the clinical setting. This study examines the sensitivity, specifi city and accuracy of the ALS Cognitive Behavioral Screen (ALS-CBS ™). We administered the measure to 112 ALS patients, including 31 who also underwent comprehensive neuropsychological testing. Screen results were validated by determining the accuracy against the full battery. Optimal cut-off scores for predicting the correct diagnosis were determined, and mean scores were compared between patients, controls and different diagnostic groups. The results demonstrated that mean cognitive scores differed between ALS and normal controls ( p Ͻ0.0001). The cognitive section differentiated ALS-FTD from other ALS patients with 100% accuracy. Cognitively normal ALS patients could be distinguished from those with any cognitive defi cit with 71% specifi city and 85% sensitivity. A separate behavioral score was signifi cantly lower in the ALS cohort compared to controls ( p Ͻ0.0001) and predicted ALS-FTD with 80% sensitivity and 88% specifi city. In conclusion, the ALS-CBS™ can aid in detecting cognitive and behavioral impairment in a clinical setting, although it does not replace formal diagnostic assessment. Further validation with larger sample sizes will clarify its clinical utility.