Complaints of forgetfulness in women approaching menopause may not reflect actual memory loss but instead may be linked to mood, reported researchers at the 34th Annual Meeting of the International Neuropsychological Society. A total of 24 perimenopausal women between 40 and 60 were examined for cognitive function, mood, and psychosocial and health status during the early follicular to midfollicular phase. One participant had clinical evidence of memory impairment, while several performed lower than expected on cognitive measures. However, although none met clinical criteria for mood disorder, all women reported symptoms of mood disruption, and 15 showed symptoms of mild to moderate depression and/or anxiety. The researchers also found a significant relationship between mood state, complaints of forgetfulness, and encoding, as well as between mood state and estradiol levels.

Alzheimer’s disease is highly genetic, according to a study published in the February Archives of General Psychiatry. Investigators screened for cognitive dysfunction in 11,884 twin pairs 65 and older in the Swedish Twin registry; 392 pairs included at least one member with Alzheimer’s disease. Results showed that heritability for Alzheimer’s disease was estimated to be 58% in a full model and 79% in a best-fitting model. After controlling for age, the researchers found no significant difference between men and women in prevalence or heritability for Alzheimer’s disease. Although the findings indicate that heritability is high and the same genetic risk factors are influential for both men and women, nongenetic risk factors also play an important role, the investigators stated.

Tetrabenazine appears to be effective in lessening chorea in ambulatory patients with Huntington’s disease, as reported in the February 14 Neurology. A total of 84 ambulatory patients with Huntington’s disease were randomized to receive tetrabenazine or placebo for 12 weeks, with dosages increasing over seven weeks to a maximum of 100 mg/day, or until treatment effect was achieved or adverse effects proved intolerable. Treatment with tetrabenazine resulted in a reduction of 5.0 units in chorea severity compared with a reduction of 1.5 units with placebo, per the Unified Huntington’s Disease Rating Scale. A significant benefit on ratings of clinical global improvement was also observed. "Tetrabenazine should be dosed individually based on ongoing assessment of possible adverse side effects," noted the researchers.

Guidelines for stroke patients based largely on results from the Peridopril Protection Against Recurrent Stroke Study (PROGRESS) may not be applicable to a typical primary care stroke population, according to findings published February 24 in the online BMJ. Investigators compared the characteristics of patients with a validated history of stroke or transient ischemic attack with those of participants in the PROGRESS trial. They found that patients were 12 years older than PROGRESS participants and twice as likely to be women, while the median time that had elapsed since their cerebrovascular event was two and one-half years, compared with eight months for PROGRESS trial participants. The researchers urged that "further evidence should be collected on the efficacy and adverse effects of intensive blood pressure lowering in representative populations."

Patients with Alzheimer’s disease who have higher levels of education experience faster cognitive decline, according to the March Journal of Neurology, Neurosurgery, and Psychiatry. A total of 312 persons 65 and older were diagnosed with incident Alzheimer’s disease and were followed overall for 5.6 years. Participants received an average of 3.7 neuropsychological assessments consisting of 12 individual tests. Results showed that composite cognitive performance declined by 9% of a standard deviation per year, and rates of decline before and after Alzheimer’s disease incidence were similar. The investigators reported that for each additional year of education there was 0.3% standard deviation lower composite cognitive performance per year of follow-up. The association between higher education and faster decline was noted primarily in the executive speed and memory cognitive domains.

Neuronal transplantation in Huntington’s disease provides a period of several years of improvement and stability, but not a permanent cure for the disease, according to a report published in the February 27 Lancet Neurology. Researchers assessed five patients with Huntington’s disease annually for up to six years after neural grafting. Clinical improvement plateaued after two years and then faded off variably four to six years after surgery. Dystonia deteriorated consistently, while chorea did not; cognitive performance remained stable on nontimed tests, and progression of motor disability showed deterioration on timed tests. Two patients who had no benefit from grafting at two years continued to show decline in the same way as nongrafted patients.

Tinnitus may reduce cognitive capacity needed to perform tasks that require voluntary, conscious, effortful, and strategic control, according to the February Journal of Speech, Language, and Hearing Research. Nineteen participants with chronic moderate tinnitus were matched with controls for age, education, and verbal IQ and completed auditory verbal working-memory and visual divided-attention tasks. Reading span of the tinnitus group was significantly shorter than that of the control group, and the tinnitus group recorded slower reaction times and poorer accuracy in the most demanding dual-task context. "Future research should investigate effects of severe tinnitus and possible effects of hearing loss," the investigators stated.

The recently identified B2 compound might lessen cellular pathology in Huntington’s and Parkinson’s diseases, potentially offering a therapeutic approach to treating both diseases, according to the March 14 Proceedings of the National Academy of Sciences. Investigators identified the B2 compound’s ability to increase inclusion formation of the proteins associated with Huntington’s and Parkinson’s diseases. The B2 compound prevented huntingtin-mediated proteasome dysfunction, as well as reduced a–synuclein-mediated toxicity. Together, these findings indicate that the accumulation of misfolded proteins may not be the primary toxic mechanism underlying neurodegenerative diseases. Investigators suggested that therapies promoting inclusion formation might represent a unique therapeutic approach for both Huntington’s and Parkinson’s diseases.

Treatment of prehypertension with candesartan may reduce the risk of progression to hypertension, according to a study published in the March 14 online New England Journal of Medicine. Researchers randomly assigned participants to receive two years of candesartan or placebo, followed by two years of placebo for both groups. Participants had repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg. Hypertension developed in 53 out of 391 participants in the candesartan group and 154 out of 381 participants in the placebo group during the first two years. After four years, hypertension developed in 208 of those in the candesartan group and 240 of those in the placebo group. In addition, serious adverse events occurred in 3.5% of the participants in the candesartan group and 5.9% of those receiving placebo.

Researchers have discovered a protein found only in cerebrospinal fluid that may help identify a subgroup of patients with multiple sclerosis, according to a report in the February Annals of Neurology. Cerebrospinal fluid analysis was performed in 29 patients with multiple sclerosis or clinically isolated syndromes, 27 patients with transverse myelitis, 50 patients with HIV infection, and 27 patients with other neurologic diseases. The researchers found a unique protein that was 100% specific for patients with multiple sclerosis or clinically isolated symptoms compared with patients with transverse myelitis or other neurologic diseases. In addition, low levels of this protein, identified as a cleavage product of full-length cystatin C, were found in some patients with HIV infection. "Cleavage of cystatin C may be an adaptive host response and may identify a subgroup of patients with multiple sclerosis," concluded the researchers.

The combination therapy of atorvastatin and glatiramer acetate could prove to be effective for treating patients with multiple sclerosis, according to the March 16 online Journal of Clinical Investigation. Researchers administered the combination therapy using suboptimal doses in mice with experimental autoimmune encephalomyelitis. Results showed that the therapy prevented or reversed clinical and histologic experimental autoimmune encephalomyelitis. In addition, secretion of proinflammatory T^h1 cytokines was reduced in mice with combination therapy, but not in mice treated with each drug alone at the same doses. The researchers stated, "Our results demonstrate that agents with different mechanisms of immune modulation can combine in a synergistic manner for the treatment of central nervous system autoimmunity and provide rationale for testing the combination of atorvastatin and glatiramer acetate in multiple sclerosis."

Investigators have found that in a study of 40 patients with amyotrophic lateral sclerosis, nearly one third showed evidence of cognitive impairment in a pattern consistent with frontotemporal lobar dementia. As reported in the March Archives of Neurology, the participants underwent baseline neurologic and neuropsychologic examinations; cognitive test performance was compared in patients with amyotrophic lateral sclerosis and matched controls. Twelve patients showed evidence of cognitive impairment, and nine met the neuropsychologic criteria for dementia. Patients with amyotrophic lateral sclerosis and dementia showed predominant impairment in free recall, executive function, and naming. In addition, the researchers observed an association between increasing amyotrophic lateral sclerosis severity and declining verbal fluency performance. However, cognitive performance was not related to site of onset or survival, said the researchers.

Elderly persons taking anticholinergic drugs may experience mild cognitive impairment, reported researchers in the February 1 online BMJ. A total of 372 persons older than 60 without dementia underwent cognitive examinations and neurologic assessments. A total of 9.2% of participants continuously used anticholinergic drugs during the year before cognitive assessment, and had poorer performance on reaction time, attention, delayed nonverbal memory, narrative recall, visuospatial construction, and langauge tasks than did those not using anticholinergic drugs. In addition, 80% of users were classified as having mild cognitive impairment, compared with 35% of nonusers, and anticholinergic drug use was a strong predictor of mild cognitive impairment. The researchers concluded, "Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors."

Use of MRI to confirm multiple sclerosis on the basis of a single attack of neurologic dysfunction may lead to overdiagnosis and overtreatment, as reported in the March 24 online BMJ. Investigators performed a systematic review of 29 studies on accuracy of diagnosis that compared MRI, or diagnostic criteria incorporating such imaging, to a reference standard for the multiple sclerosis diagnosis. Results demonstrated that among 15 studies of higher methodologic quality, those with longer follow-up produced higher estimates of specificity and lower estimates of sensitivity, and only two such studies followed patients for more than 10 years. In addition, MRI could not accurately rule in multiple sclerosis in the presence of many lesions, and the absence of lesions was of limited use in ruling out a multiple sclerosis diagnosis.

Controlled inflammatory response may restore damaged myelin and nerve function in patients with multiple sclerosis, according to findings published in the March 23 online Journal of Clinical Investigation. Researchers injected interleukin 4–activated microglia into the cerebrospinal fluid of rodents with experimental autoimmune encephalomyelitis, resulting in increased oligodendrogenesis in the spinal cord and improved clinical symptoms. "The newly formed oligodendrocytes were spatially associated with microglia expressing major histocompatability complex class II proteins and insulin-like growth factor I," stated the investigators, noting that their findings "point to what we believe to be a novel role for microglia in oligodendrogenesis from the endogenous stem cell pool."

Calcium-activated potassium channels may constitute a potential therapeutic target in episodic ataxia type 2, as reported in the March Nature Neuroscience. Investigators found a gene-dependent loss of the precision of pacemaking in Purkinje cells using mouse models of ataxia type 2. The irregular pacemaking was caused by reduced activation of calcium-activated potassium channels and was reversed by pharmacologically increasing their activity with 1-ethyl-2-benzimidazolinone, the investigators reported. In addition, chronic in vivo perfusion of 1-ethyl-2-benzimidazolinone into the cerebellum of ataxic mice significantly improved motor performance. "Our data support the hypothesis that the precision of intrinsic pacemaking in Purkinje cells is essential for motor coordination," the investigators stated.

Traditional risk factors for cardiovascular disease may also be risk factors for cognitive decline, according to a report in the February 21 online Alzheimer’s and Dementia. Researchers conducted a survey of large cohort studies that included participants predominantly 65 and older. A total of 96 papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, especially those previously associated with an increased risk of cardiovascular disease. "There is some evidence from observational studies that treating elevated levels of blood pressure may reduce the risk for cognitive impairment," although randomized trial results were mixed, noted the researchers.

Progress has been made in developing effective gene-silencing therapeutics for synucleinopathies, including Parkinson’s disease, as reported in the online January Experimental Neurology. Researchers identified a 21-nucleotide sequence in the coding region of human a-synuclein that constitutes an effective target for robust silencing by vector-based RNA interference (RNAi). In addition, the team demonstrated effective silencing of endogenous human a-synuclein in vitro in the human dopaminergic cell line SH-SY5Y, as well as of experimentally expressed human a-synuclein in vivo in the brains of rats. The researchers concluded that their findings "demonstrate potent silencing of human a-synuclein expression in vitro and in vivo by viral vector-based RNAi."

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