Retrograde amnesia for semantic information in Alzheimer's disease

Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde amnesia within semantic memory. No evidence for a gradient within this amnesia was found, although one was present on an autobiographic test of retrograde amnesia that had a wider time scale. Several explanations for these results are presented, including one that suggests that extended retrograde amnesia and semantic memory deficits are in fact one and the same defici

Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

Background and Purpose-White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. Methods-A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Results-Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P = 0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Conclusions-Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease. (Stroke. 2010;41:554-556.

Infratentorial Abnormalities in Vascular Dementia

Background and Purpose—Infratentorial abnormalities may cause cognitive deficits, but current research criteria for vascular dementia (VaD) do not consider them. Our purposes were to determine the prevalence of infratentorial abnormalities in VaD, their relation with supratentorial abnormalities, and whether they are relevant to cognition. Methods—We examined 182 patients (120 men, mean age 73 years, SD 8) with probable VaD at inclusion into a multicenter clinical trial. MRI scans were evaluated for infratentorial vascular abnormalities, midbrain atrophy, cerebellar atrophy, basilar artery diameter and tortuosity, and supratentorial abnormalities. Cognitive testing included the mini–mental state examination (MMSE) and the vascular dementia assessment scale (VaDAS-cog). Results—One hundred forty-one (77.5%) patients had infratentorial abnormalities: 119 (65.4%) had focal infratentorial vascular lesions, 65 (35.7%) had diffuse pontine vascular abnormalities hyperintense on T2-weighted images, 20 (11.0%) had midbrain atrophy, and 16 (8.8%) had cerebellar atrophy. Significant correlations were found between number of infratentorial vascular lesions and basilar artery diameter (rs 0.26; P 0.0001), infratentorial and basal ganglia (including thalamus) vascular abnormalities (rs 0.30; P 0.0001), as well as between midbrain atrophy and global supratentorial atrophy (rs 0.27; P 0.0001). Infratentorial vascular abnormalities and cerebellar atrophy were not significantly associated with cognitive impairment. Patients with midbrain atrophy performed worse on cognitive tests than those without midbrain atrophy. After correction for sex, age, education, supratentorial abnormalities, and center, midbrain atrophy remained significantly associated with lower MMSE scores (P 0.05). Conclusions—Infratentorial abnormalities often occur in patients with VaD, but only midbrain atrophy was found to be relevant to cognitio

Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease

Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. Methods This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. Discussion We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function

Thalamic Lesions in Vascular Dementia: Low Sensitivity of Fluid-Attenuated Inversion Recovery (FLAIR) Imaging

Background and Purpose—The criteria of the National Institute of Neurological Disorders and Stroke (NINDS)– Association Internationale pour la Recherche et l’Enseignement en Neurosciences (AIREN) include thalamic lesions for the diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2-weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity of these sequences to depict thalamic lesions. Methods—We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology. Results—The total number of thalamic lesions was 214. Two hundred eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR ( 2 5.1; P 0.05). Although the mean size of lesions detected on T2-WI and not on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected on both sequences (6.7 mm) (P 0.001), 5 of the 29 lesions 10 mm on T2-WI were not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic lesions and 30 (60%) of the 50 probable microbleeds. Conclusions—FLAIR should not be used as the only T2-weighted sequence to detect thalamic lesions in patients suspected of having VaD

Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease

Introduction Alzheimer's disease (AD) is associated with synapse loss. Souvenaid, containing the specific nutrient combination Fortasyn Connect, was designed to improve synapse formation and function. The NL-ENIGMA study explored the effect of Souvenaid on synapse function in early AD by assessing cerebral glucose metabolism (CMRglc) with 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET). Methods We conducted an exploratory double-blind randomized controlled single-center trial. Fifty patients with mild cognitive impairment or mild dementia with evidence of amyloid pathology (cerebrospinal fluid or PET) were stratified for MMSE (20–24 and 25–30) and randomly 1:1 allocated to 24-week daily administration of 125 mL Souvenaid (n = 25) or placebo (n = 25). Dynamic 60-minute [18F]FDG-PET scans (21 frames) with arterial sampling were acquired at baseline and 24 weeks. CMRglc was estimated by quantitative (Ki) and semiquantitative (standardized uptake value ratio, reference cerebellar gray matter) measurements in five predefined regions of interest and a composite region of interest. Change from baseline in CMRglc was compared between treatment groups by analysis of variance, adjusted for baseline CMRglc and MMSE stratum. Additional exploratory outcome parameters included voxel-based analyses by Statistical Parametric Mapping. Results No baseline differences between treatment groups were found (placebo/intervention: n = 25/25; age 66 ± 8/65 ± 7 years; female 44%/48%; MMSE 25 ± 3/25 ± 3). [18F]FDG-PET data were available for quantitative (placebo n = 19, intervention n = 18) and semiquantitative (placebo n = 20, intervention n = 22) analyses. At follow-up, no change within treatment groups and no statistically significant difference in change between treatment groups in CMRglc in any regions of interest were found by both quantitative and semiquantitative analyses. No treatment effect was found in the cerebellar gray matter using quantitative measures. The additional Statistical Parametric Mapping analyses did not yield consistent differences between treatment groups. Discussion In this exploratory trial, we found no robust effect of 24-week intervention with Souvenaid on synapse function measured by [18F]FDG-PET. Possible explanations include short duration of treatment