Hedvig Söderlund

High prevalence of white matter hyperintensities in normal aging: relation to blood pressure and cognition.

The occurrence of cerebral white matter hyperintensities (WMHs), and their associations with blood pressure, episodic memory, and other cognitive tasks, were examined in a population-based sample of 123 individuals between 64 and 74 years old. Magnetic Resonance Imaging (MRI) detected subcortical and periventricular hyperintensities in 90% and 67% of the cases, respectively. Subcortical WMHs were related to elevated diastolic blood pressure measured ten years earlier, and periventricular WMHs were related to elevated diastolic blood pressure measured five and ten years earlier. Subcortical hyperintensities were weakly associated with impaired motor speed, but this association was not significant. Periventricular WMHs had a negative effect on episodic memory, although the relation was not linear. Collectively, the notion that white matter hyperintensities impair cognitive function got weak support in this Swedish sample.

Cerebral changes on MRI and cognitive function: the CASCADE study.

The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4+/-3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies.

Remembering our origin: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization

Gender differences in spatial memory favoring men are frequently reported, and the involvement of the hippocampus in these functions is well-established. However, little is known of whether this behavioral gender difference is mirrored in a gender difference in hippocampal function. Here we assessed hippocampal activity, using functional MRI, while 24 men and women moved through three-dimensional virtual mazes (navigation phase) of varying length, and at the end-point estimated the direction of the starting-point (pointing phase). Men were indeed more accurate than women at estimating direction, and this was especially true in longer mazes. Both genders activated the posterior hippocampus throughout the whole task. During the navigation phase, men showed a larger activation in the right hippocampus than women, while in the pointing phase, women showed a larger activation in the left hippocampus than men. Right-lateralized activation during the navigation phase was associated with greater task performance, and may reflect a spatial strategy that is beneficial in this task. Left-sided activation during the pointing phase might reflect a less efficient post hoc verbal recapitulation of the route. This study is the first to identify neural correlates of the commonly observed male advantage in recalling ones original position, and points to hippocampal lateralization as a possible explanation for this behavioral gender difference.

As time goes by : Hippocampal connectivity changes with remoteness of autobiographical memory retrieval

The hippocampus is crucial for episodic autobiographical memory retrieval. Functional neuroimaging evidence suggests that it is similarly engaged in recent and remote retrieval when memories are matched on vividness and personal importance. Far fewer studies have investigated the nature of hippocampal‐neocortical coactivation in relation to memory remoteness. The purpose of this study was to examine hippocampal activity and functional connectivity as a function of memory age. Unlike most studies of autobiographical memory, we included autobiographical memories formed in the days and weeks before scanning, in addition to truly remote memories on the order of months and years. Like previous studies, we found that the hippocampus was active bilaterally regardless of memory age, with anterior activity increasing up to 1 yr and then decreasing, and with posterior activity being less sensitive to memory age. More importantly, hippocampal functional connectivity varied with memory age. Retrieving recent memories (≤1 yr) showed a late coactivation of the hippocampus and areas of the autobiographical memory network, whereas retrieving remote memories (10 yrs) showed an early negative coactivation of the hippocampus and left inferior frontal gyrus followed by a positive coactivation with anterior cingulate. This finding may reflect that the hippocampus is more strongly integrated with the autobiographical memory network for recent than for remote memories, and that more effort is required to recover remote memories.

Acute effects of alcohol on neural correlates of episodic memory encoding.

Although it is well established that alcohol impairs episodic memory encoding, it is unknown how this occurs on a cerebral level. We scanned intoxicated and sober individuals with functional magnetic resonance imaging (fMRI) while they encoded various materials that were recalled the following day. Alcohol impaired memory for object pairs and face-name pairs, but not for words and phrase-word pairs. Impaired performance was associated with reduced bilateral prefrontal activation and non-specific activation of the parahippocampal gyrus. These results suggest that alcohol impairs episodic memory by interfering with activity of regions involved in encoding, and further indicate which regions are critical for human memory.

Severely deficient autobiographical memory (SDAM) in healthy adults: A new mnemonic syndrome

Recollection of previously experienced events is a key element of human memory that entails recovery of spatial, perceptual, and mental state details. While deficits in this capacity in association with brain disease have serious functional consequences, little is known about individual differences in autobiographical memory (AM) in healthy individuals. Recently, healthy adults with highly superior autobiographical capacities have been identified (e.g., LePort, A.K., Mattfeld, A.T., Dickinson-Anson, H., Fallon, J.H., Stark, C.E., Kruggel, F., McGaugh, J.L., 2012. Behavioral and neuroanatomical investigation of Highly Superior Autobiographical Memory (HSAM). Neurobiol. Learn. Mem. 98(1), 78-92. doi: 10.1016/j.nlm.2012.05.002). Here we report data from three healthy, high functioning adults with the reverse pattern: lifelong severely deficient autobiographical memory (SDAM) with otherwise preserved cognitive function. Their self-reported selective inability to vividly recollect personally experienced events from a first-person perspective was corroborated by absence of functional magnetic resonance imaging (fMRI) and event-related potential (ERP) biomarkers associated with naturalistic and laboratory episodic recollection, as well as by behavioral evidence of impaired episodic retrieval, particularly for visual information. Yet learning and memory were otherwise intact, as long as these tasks could be accomplished by non-episodic processes. Thus these individuals function normally in day-to-day life, even though their past is experienced in the absence of recollection.

Sex differences in volume and structural covariance of the anterior and posterior hippocampus

Sex differences in episodic and spatial memory are frequently observed, suggesting that there may be sex-related structural differences in the hippocampus (HC). Earlier findings are inconsistent, possibly due to a known variability along the hippocampal longitudinal axis. Here, we assessed potential sex differences in hippocampal volume and structural covariance with the rest of the brain in young men and women (N=76), considering the anterior (aHC) and posterior (pHC) hippocampus separately. Women exhibited a larger pHC than men adjusted for brain size. Using partial least squares, we identified two significant patterns of structural covariance of the aHC and pHC. The first included brain areas that covaried positively and negatively in volume with both the aHC and pHC in men, but showed greater covariance with the aHC than pHC in women. The second pattern revealed distinct structural covariance of the aHC and pHC that showed a clear difference between men and women: in men the pHC showed reliable structural covariance with the medial and lateral parietal lobes and the prefrontal cortex, whereas in women the aHC showed reliable structural covariance with the anterior temporal lobe bilaterally. This pattern converges with resting state functional connectivity of the aHC and pHC and suggests that these hippocampal sections interact with different brain regions, consistent with a division of labor with regards to episodic and spatial memory. Our findings lend support to a division of the HC into an anterior and posterior part and identify sex as a potential moderating factor when investigating hippocampal structure and connectivity.

Cerebral atrophy as predictor of cognitive function in old, community-dwelling individuals

Objectives – The impact of cortical and subcortical atrophy on cognitive function was examined in a sample of older community‐dwelling men and women.

Shorter telomere length is linked to brain atrophy and white matter hyperintensities

BACKGROUND leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging. METHODS we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years. RESULTS shorter TL was related to greater degree of subcortical atrophy (β = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs. CONCLUSION this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain.

Cognitive test battery of CASCADE : Tasks and data.

Abstract This paper presents the cognitive test battery used in the Cascade Study (Cardiovascular Determinants of Dementia) for examining the consequences of cerebral white matter lesions and atrophy. The test battery includes nine different tasks assessing memory, executive function, and global cognitive function. Three episodic memory tasks were used in combinations to assess the role of attention and speed on encoding. Estimates of short- and long-term memory capacity were also derived from these three memory tasks. Semantic memory production / frontal lobe functions were assessed by means of a word fluency test. The Letter Digit Substitution test and the Stroop test were used to assess speed of processing and attention. Motor speed was measured with the Purdue Pegboard test, and global cognitive function was assessed by the Mini Mental State Examination. Overall performance data for the whole Cascade sample and for each of eight study centers are presented for each test. Possible reasons for performance differences among study centers are discussed.