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Aim: To explore patterns of cerebral blood flow in patients with mild cognitive impairment (MCI), who (1) eventually deteriorate into overt dementia, with no particular focus on the type of dementia, or (2) do not appear to further deteriorate in their cognitive functions. Methods: Thirty-seven MCI patients, with or without vascular pathology, were studied prospectively. The patients underwent 99mTc-HMPAO SPECT analysis at baseline. Possible clinical conversion into dementia within a 2-year period was assessed. Results: Nineteen patients had progressive MCI (PMCI), while 18 patients were considered clinically stable (SMCI). PMCI patients had more often abnormally low cerebral blood flow in at least one of the frontal, temporal, parietal or occipital lobes compared to SMCI patients (12/19 vs. 5/18; p = 0.049). At least one of the temporal regions was found to be abnormal in 9 PMCI patients in contrast to only 1 SMCI patient (p = 0.008). More specifically, blood flow in the medial portion of the left temporal region was abnormal in 8 PMCI patients, a pattern seen in 1 SMCI patient only (p = 0.019). Conclusion: The results suggest that blood flow reductions particularly in the left medial temporal region indicate an elevated risk of further cognitive decline in MCI patients.

Background: Novel biomarkers are important for identifying as well as differentiating subcortical vascular dementia (SVD) and Alzheimer’s disease (AD) at an early stage in the disease process. Methods: In two independent cohorts, a multiplex immunoassay was utilized to analyze 90 proteins in cerebrospinal fluid (CSF) samples from dementia patients and patients at risk of developing dementia (mild cognitive impairment). Results: The levels of several CSF proteins were increased in SVD and its incipient state, and in moderate-to-severe AD compared with the control group. In contrast, some CSF proteins were altered in AD, but not in SVD. The levels of heart-type fatty acid binding protein (H-FABP) were consistently increased in all groups with dementia but only in some of their incipient states. Conclusions: In summary, these results support the notion that SVD and AD are driven by different pathophysiological mechanisms reflected in the CSF protein profile and that H-FABP in CSF is a general marker of neurodegeneration.

Background: Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer’s disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy. Methods: The Gothenburg MCI study is a clinically based longitudinal study with biennial clinical assessments. The participants (n = 166) consist of 92 patients with stable MCI, 30 patients with converting MCI, and 44 healthy controls. WML volumes was measured manually using MRIcron. Automated segmentation of hippocampal and total white matter volumes was performed using FreeSurfer. Results: The patients converting from MCI to dementia had reduced hippocampal volume. Stable MCI patients had fewer WML and converting MCI patients had more WML compared to controls. Hippocampal volume was only correlated to WML volume (ρ = 0.57; p < 0.01) in the quartile (n = 42) with the most WML. Conclusions: Hippocampal atrophy is present in both AD and SVD. Hippocampal volume was associated with WML volume only in the high WML quartile, suggesting that the WML volume must reach a threshold before hippocampal atrophy is seen.

Background/Aim: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. Methods: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), β-amyloid 1–42 (Aβ42) and the light subunit of neurofilament protein (NFL) were determined. Results: Patients with converting MCI and stable dementia had lower CSF Aβ42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. Conclusion: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.

Background: Alterations in interrelated endocrine axes may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia. Methods: Salivary cortisol before and after a 0.5-mg dexamethasone test, and serum levels of thyroid-stimulating hormone, total thyroxine (T4), free T4, total triiodothyronine (TT3), estradiol, testosterone and insulin-like growth factor 1 were measured in 43 MCI cases and 26 healthy controls. All participants underwent a comprehensive neuropsychological test battery covering the cognitive domains of speed/attention, memory, visuospatial functions, language and executive functions. Results: The MCI group did not differ in basal levels of endocrine markers compared to controls. Among those with MCI, TT3 levels were inversely associated with cognitive performance across all domains. After stratifying MCI cases according to TT3 levels, those with relatively high TT3 levels showed impairment in memory as well as in visuospatial and executive functions. Those with TT3 levels at or below the lower boundary of the normal range performed comparably to healthy controls. Other endocrine markers were not related to cognitive performance. Conclusions: Among those with MCI, TT3 was associated with a neuropsychological profile typical of prodromal Alzheimer’s disease. While the mechanisms remain unclear, optimal levels of thyroid hormone under a compromising condition such as MCI and related neuropathology need reconsideration.

Background: Mild cognitive impairment (MCI) is a heterogeneous condition, and the prognosis differs within the group. Recent findings suggest that hippocampal volumetry and CSF biomarkers can be used to predict which MCI patients have an underlying neurodegenerative disorder. Objective: To examine the combined predictive value of hippocampal volume and CSF levels of total tau (T-tau) and β-amyloid42 (Aβ42) in stable and converting MCI patients. The participants (n = 68) included patients with MCI at baseline and who converted to dementia by the time of the 2-year follow-up (n = 21), stable MCI patients (n = 21) and healthy controls (n = 26). Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually, based on data from the 0.5-tesla MRI investigations at baseline. Baseline CSF levels of T-tau and Aβ42 were measured using commercially available, enzyme-linked immunosorbent assays. Results: The converting MCI group had significantly smaller left hippocampi, lower CSF Aβ42 and higher T-tau compared to both the stable MCI group and the healthy controls. Multivariate analysis revealed that a combination of the variables outperformed the prognostic ability of the separate variables. Conclusions: Hippocampal volumes supplement the prognostic accuracy of CSF Aβ42 and T-tau in MCI.

Objective: To study which cognitive profiles of incipient dementia strongest predict the conversion to Alzheimer’s disease (AD) and mixed dementia (MD)/vascular dementia (VaD). Methods: 260 subjects with mild cognitive impairment (MCI) were included in the study and 209 (79%) were followed up after 2 years. At baseline, the subjects were assessed with a neuropsychological battery covering the cognitive domains speed/attention, memory, visuospatial, language and executive functions. Results: After 2 years, 9 subjects were considered normal, 148 had stationary MCI and 47 (23%) had converted to dementia. Twenty subjects were diagnosed with AD, 15 with MD and 9 with VaD. The others were 2 with unspecified dementias and 1 with primary progressive aphasia. Dementia converters had a high proportion of impairment in all cognitive domains. The profiles of incipient AD and MD/VaD differed, with memory, visuospatial and language symptoms preceding AD, and executive and speed/attention symptoms preceding MD/VaD. Conclusions: The risk of converting to dementia is increased when domains in addition to memory are impaired. The incipient AD and MD/VaD profiles differed quite clearly. Considering that the vascular group consisted of a majority of patients with MD, the differences are convincing – vascular disease seems to have an essential impact on cognition.

Background: Mild cognitive impairment (MCI) is an etiologically unclear disorder. Cerebrospinal fluid (CSF) biomarkers are potentially useful for the differentiation between various MCI etiologies. Aim: The aim of the study was to assess whether baseline CSF hyperphosphorylated tau (P-tau), total tau (T-tau), amyloid β 1–42 (Aβ42) and neurofilament light (NF-L) in patients with MCI could predict subcortical vascular dementia (SVD) and Alzheimer’s disease (AD) at follow-up. Methods: Biomarker levels were assessed by Luminex xMAP technology and ELISA. Results: Increased baseline concentrations of NF-L significantly separated MCI-SVD from stable MCI. The MCI-SVD patients were inseparable from stable MCI but separable from patients developing AD (MCI-AD) on the basis of Aβ42, T-tau and P-tau181 levels. Conclusion: A combination of the biomarkers Aβ42, T-tau, P-tau181 and NF-L has the potential to improve the clinical separation of MCI-SVD patients from stable MCI and MCI-AD patients.

Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and β-amyloid42 (Aβ42) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer’s disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to controls and FTD (p < 0.001 for both). CSF-GAP-43 was increased in AD compared to controls (p < 0.05), and both CSF-GAP-43 and CSF-sAPP were increased in AD compared to FTD (p < 0.01). Positive and highly significant correlations were found between CSF-tau and CSF-GAP-43 in all groups and between CSF-tau, CSF-GAP-43 and CSF-sAPP in AD. The correlations found may reflect a common pathophysiologic process such as axonal degeneration.

The aim was to study the frequently found white-matter changes on computerized tomography (CT) in patients with dementia and to relate these changes to clinical regional brain symptomatology, vascular factors, albumin ratio [indicator of blood-brain barrier (BBB) function] and other CT changes. The study included 85 patients, average age 71 ± 8, with Alzheimer’s disease (n = 56) and vascular dementia (n = 29), who underwent CT (Siemens Somatome DR 1) of the brain. They were inpatients in a psychiatric department specialized in dementia investigations. The degree of CT white-matter changes (absence, mild-moderate, severe) was the basis for the division of the patients into three groups. As the patients without white-matter changes were significantly younger than those with such changes, all statistical analyses were controlled for age. Subcortical symptomatology was significantly more frequent in the group with severe white-matter changes, whereas the reverse was true for parietal symptomatology. Diabetes mellitus, hypertension, ischemic cardiac disease and lacunas were significantly more common in patients with white-matter changes, whereas the freqeuncy of transient ischemic attack/stroke episodes did not differ significantly between the groups. The albumin ratio was significantly higher in the groups with white-matter changes and highest in the group with severe white-matter changes. The findings indicate that white-matter changes in demented patients are at least partially an age- and stroke-independent disease manifestation of the vascular system and is associated with a specific symptom pattern. BBB dysfunction may be the link between the vasculature and the tissue damage.