[The correlation of functional connectivity and structural connectivity between hippocampus and thalamus in Alzheimer's disease and amnestic mild cognitive impairment].

Objective: To investigate the correlation of functional connectivity (FC) and the integrity of connective fibres between hippocampus and thalamus in Alzheimer's disease(AD) and amnestic mild cognitive impairment (aMCI). Methods: Both resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data of 40 AD patients, 37 aMCI patients and 41 normal control subjects matching with age and educational level were collected. These subjects were all recruited from outpatient Department of Neurology in the Second Medical Center of Chinese PLA General Hospital, as well as poster, from May 2016 to January 2018. The FC strength between bilateral hippocampus and thalamus, as well as the parameters representing integrity of connective fibres, including fractional anisotropy (FA) and mean diffusivity(MD),were analyzed. Also, the correlations between FC strength and FA or MD strength were analyzed in the study. Results: Compared to that of normal control subjects, the FC strength between billateral hippocampus and thalamus in patients with AD, aMCI were not significantly different(P>0.05). The integrity of bilateral connective fibres between hippocampus and thalamus were damaged in AD patients when compared to normal control subjects(P<0.01). A positive correlation of connective fibres integrity with FC strength between hippocampus and thalamus was found in the left side(r=0.25,P<0.05) but rather in the right side. Conclusion: In AD and aMCI patients, structural connectivity between left hippocampus and thalamus affects the functional connectivity between them.

Network-wide abnormalities explain memory variability in hippocampal amnesia.

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n = 38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience.

Neurocognitive and Behavioral Indexes for Identifying the Amnestic Subtypes of Mild Cognitive Impairment.

Early identification of amnestic mild cognitive impairment (aMCI) subtypes is important for early diagnosis and prognosis of Alzheimer's disease. Healthy, single-domain (sdaMCI) and multiple-domain aMCI (mdaMCI) participants performed an auditory-visual distraction-attention task. Event-related brain potentials (ERPs) were recorded while the participants performed the task to evaluate Go/NoGo N2 and P3 ERP components. The results showed the expected behavioral and cognitive decline in mdaMCI participants relative to controls (fewer hits, longer reaction times [RTs], slightly smaller Go-N2 and NoGo-N2 amplitudes), while sdaMCI participants showed some decline (slightly longer RTs, smaller Go- and NoGo-N2 amplitudes) along with some unexpected results (a late positive slow wave, PSW) and good levels of execution. In addition, some of these parameters proved to be useful markers. Thus, the number of hits was the best marker for diagnosing mdaMCI participants (distinguishing them from controls, from sdaMCI participants, and from both groups together), while the PSW amplitude was the best marker for diagnosing sdaMCI participants (distinguishing them from controls, and from control & mdaMCI participants).

Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3ß level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

Changes in thalamic connectivity in the early and late stages of amnestic mild cognitive impairment: a resting-state functional magnetic resonance study from ADNI.

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer's disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.

Using pictures and words to understand recognition memory deterioration in amnestic mild cognitive impairment and Alzheimer's disease: a review.

Difficulty recognizing previously encountered stimuli is one of the earliest signs of incipient Alzheimer's disease (AD). Work over the last 10 years has focused on how patients with AD and those in the prodromal stage of amnestic mild cognitive impairment make recognition decisions for visual and verbal stimuli. Interestingly, both groups of patients demonstrate markedly better memory for pictures over words, to a degree that is significantly greater in magnitude than their healthy older counterparts. Understanding this phenomenon not only helps to conceptualize how memory breaks down in AD, but also potentially provides the basis for future interventions. This review critically examines recent recognition memory work using pictures and words in the context of the dual-process theory of recognition and current hypotheses of cognitive breakdown in the course of very early AD.

Vascular thalamic amnesia: a reappraisal.

In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided lesions and 41 with bilateral lesions). We aimed to find answers to the following questions concerning the vascular thalamic amnesia syndrome: (i) Which qualitative pattern of memory impairment (and associated cognitive and behavioral deficits) do these patients present? (ii) Which lesioned intrathalamic structures are primarily responsible for the amnesic syndrome? (iii) Are the recollection and familiarity components of declarative memory underlain by the same or by different thalamic structures? Results of the review indicate that, similar to patients with amnesic syndromes due to mesio-temporal lobe damage, patients with vascular thalamic amnesia display a prevalent deficit of declarative anterograde long-term memory, a less consistent deficit of declarative retrograde long-term memory and substantially spared short-term and implicit memory. Unlike mesio-temporal lobe patients, however, vascular thalamic amnesics often present dysexecutive and behavioral deficits similar to those observed in patients with frontal damage. The presence of an amnesic syndrome in patients with thalamic lacunar infarcts is strongly predicted by involvement of the mammillo-thalamic tract, which connects the anterior nuclei complex to the hippocampus proper via the fornix and the mammillary bodies. Finally, data reported in a few single cases provide support for the hypothesis that thalamic regions connected to distinct areas of the mesio-temporal lobe play differential roles in recollection and familiarity processes. The mammillo-thalamic tract/anterior nuclei axis seems primarily implicated in recollective processes, whereas the ventroamygdalofugal pathway/medio-dorsal axis primarily underlies familiarity processes.

MR imaging texture analysis of the corpus callosum and thalamus in amnestic mild cognitive impairment and mild Alzheimer disease.

BACKGROUND AND PURPOSE: TA is a branch of image processing that seeks to reduce image information by extracting texture descriptors from the image. TA of MR images of anatomic structures in mild AD and aMCI is not well-studied. Our objective was to attempt to find differences among patients with aMCI and mild AD and normal-aging subjects, by using TA applied to the MR images of the CC and the thalami of these groups of subjects. MATERIALS AND METHODS: TA was applied to the MR images of 17 patients with aMCI, 16 patients with mild AD, and 16 normal-aging subjects. The TA approach was based on the GLCM. MR images were T1-weighted and were obtained in the sagittal and axial planes. The CC and thalami were manually segmented for each subject, and 44 texture parameters were computed for each of these structures. RESULTS: TA parameters showed differences among the 3 groups for the CC and thalamus. A pair-wise comparison among groups showed differences for AD-control and aMCI-AD for the CC; and for AD-control, aMCI-AD, and aMCI-control for the thalamus. CONCLUSIONS: TA is a useful technique to aid in the detection of tissue alterations in MR images of mild AD and aMCI and has the potential to become a helpful tool in the diagnosis and understanding of these pathologies.

Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention.

Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease.

Diagnosing dissociative disorders.

The increasing prevalence of dissociative disorders has spawned a range of diagnostic tools. The authors describe the use of several current methods--screening instruments, structured interviews, psychological testing, and hypnosis--and they advocate enlisting the patient as an active collaborator in the diagnostic process.

Psychogenic and physiological sequelae to hypnosis: two case reports.

Two cases of hypnotic sequelae occurring in a research context (with a non-clinical college population) are reported. Case 1 was a male who experienced retroactive amnesia following hypnosis: He was unable to recall familiar telephone numbers later that day. This was not a continuation of an earlier confusion or drowsiness (as is often found) since he indicated he was wide awake following hypnosis. Two parallels exist with previous reports: unpleasant childhood experiences with chemical anesthesia and a conflict involving a wish to experience hypnosis but a reluctance to relinquish control. Case 2 was a female who, while in hypnosis, experienced an apparent epileptic seizure that had characteristics of both petit mal and grand mal seizures. Although having a history of epilepsy, she had not had a seizure in 7 years. We suspect that the seizure was psychogenic and may have been triggered by wording used in the hypnotic scale or other similarities. Possible mechanisms are discussed and preventative recommendations are made.

Transient global amnesia and thalamic infarction.

We describe the clinical and neuroradiologic features of a patient with two episodes of transient amnesia who later developed persistent amnesia and an acute infarction in the left thalamus. The neurobehavioral manifestations were strikingly similar in all three episodes. Cranial computed tomography was normal following the first two episodes. Thalamic ischemia could explain some cases of transient global amnesia.

The paramedian diencephalic syndrome: a dynamic phenomenon.

The paramedian diencephalic syndrome is characterized by a clinical triad: hypersomnolent apathy, amnesic syndrome, and impaired vertical gaze. We studied 4 cases with computed tomography evidence of bilateral diencephalic infarctions. Each case began abruptly with hypersomnolent apathy followed by fluctuations from appropriate affect, full orientation, and alertness to labile mood, confabulation, and apathy. Speech varied from hypophonia to normal; handwriting varied from legible script to gross scrawl. Psychological testing revealed poor learning and recall, with low performance scores. In 3 patients the predominant abnormality was in downward gaze.

The syndrome of bilateral paramedian thalamic infarction.

Bilateral anterior paramedian thalamic infarction resulting from occlusion of a bilaterally distributed thalamosubthalamic paramedian artery was demonstrated on CT in two patients. Patient 1 presented with a transient coma followed by asterixis, hypersomnia, vertical gaze disturbances, profound Korsakoff amnesic syndrome, and a subcortical dementia. Patient 2, with a predominantly right-sided thalamic infarct, showed good recovery from amnesia and vertical gaze disturbances. However, patient 1 remained with severe amnesia and mild subcortical dementia at follow-up 1 year later. These and similar reported cases constitute a lacunar syndrome with characteristic clinical and CT features.