SUMMARY We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia). Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory – Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia. We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative. Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures.
Introduction: Findings regarding brain morphometry among patients with dementia and concomitant depressive symptoms have been inconsistent. Thus, the aim of the present study was to test the hypothesis that dementia and concomitant depressive symptoms are associated with structural brain changes in the temporal lobe measured with structural magnetic resonance imaging (MRI). Methods: A sample of 492 patients from Norwegian memory clinics (n = 363) and Old Age Psychiatry services (n = 129) was studied. The assessment included the Cornell Scale for Depression in Dementia (CSDD), Instrumental Activities of Daily Living Scale, Mini Mental State Examination, and MRI of the brain, processed with FreeSurfer to derive ROI measures of cortical thickness, volume, and area using the Desikan-Killiany parcellation, as well as subcortical volumes. Dementia was diagnosed according to ICD-10 research criteria. Correlates of brain morphometry using multiple linear regression were examined. Results: Higher scores on the CSDD were associated with larger cortical volume (β = 0.125; p value = 0.003) and area of the left isthmus of the cingulate gyrus (β = 0.151; p value = <0.001) across all patients. Inclusion of an interaction term (dementia × CSDD) revealed a smaller area in the left temporal pole (β = −0.345; p value = 0.001) and right-transverse temporal cortex (β = −0.321; p value = 0.001) in patients with dementia and depressive symptoms. Discussion/Conclusion: We confirm the previous findings of structural brain changes in temporal regions among patients with dementia and concomitant depressive symptoms. This may contribute to a better understanding of the mechanisms underlying depression in dementia. To the best of our knowledge, this is the largest study conducted on this topic to date.
While APOE ε4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials.To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of A 42 (pA) and APOE ε4 as risk markers in a multi-center study in Norway.In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals.Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening.Patients (n = 301) were classified as subjective cognitive decline or
Abstract Background Brain innate immune activation is associated with Alzheimer’s disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles. Methods We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline ( n = 535) and follow-up ( n = 213), between 1 and 6 years from baseline (mean 2.8 years). We measured Aβ42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A−/T−/N−, A+/T−/N−, A+/T+ or N+, or A−/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group. Results Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis ( p < 0.001, A+/T+ or N+ and A−/T+ or N+, compared to A−/T−/N−). No significant group differences were observed for the cytokines CSF MCP-1, IL-6, IL-10, IL18 or IFN-γ. Longitudinally, CSF YKL-40, fractalkine and IFN-γ were all significantly lower in stable A+/T−/N− cases (all p < 0.05). CSF sTREM2, YKL-40, clusterin, fractalkine ( p < 0.001) and MCP-1 ( p < 0.05) were all higher in T or N+, with or without amyloidosis at baseline, but remained stable over time. High CSF sTREM2 was associated with preserved cognitive function within the A+/T+ or N+ group, relative to the cognitively impaired with the same A/T/N biomarker profile ( p < 0.01). Conclusions Immune hypoactivation and reduced neuron–microglia communication are observed in isolated amyloidosis while activation and increased fractalkine accompanies tau pathology in predementia AD. Glial hypo- and hyperactivation through the predementia AD continuum suggests altered glial interaction with Ab and tau pathology, and may necessitate differential treatments, depending on the stage and patient-specific activation patterns.
Delir und Demenz zeigen als organisch bedingte psychische Störungen Gemeinsamkeiten in klinischer und neurobiologischer Hinsicht und treten häufig gemeinsam auf. Das Vorliegen der einen scheint das Risiko zur Entwicklung der jeweils anderen Störung zu erhöhen. Obwohl das Delir gerade bei älteren Patienten eine häufige Störung ist, wird es oft übersehen. Zur Diagnostik des Delirs reichen aber nicht selten eine genaue Anamnese inklusive Medikamentenanamnese, klinische Untersuchung und Bestimmung von laborchemischen Routineparametern aus. Die kausale Behandlung des Delirs ist möglich und nicht unbedingt kompliziert. Zur symptomatischen Behandlung stehen nicht-medikamentöse und medikamentöse Maßnahmen zur Verfügung. Die nicht-medikamentösen Maßnahmen werden zu einem großen Teil vom pflegenden Personal ausgeführt und beinhalten u. a. Orientierungshilfen und Balance zwischen Reizüberflutung und -deprivation. Gute Kenntnis der Symptomatologie ist entscheidend auch im Hinblick auf die Prävention (Delirfachschwester). Zur symptomatischen medikamentösen Behandlung erscheinen Neuroleptika günstig. Im Hinblick auf extrapyramidale Nebenwirkungen sind Typika den Atypika unterlegen. Der Einsatz von Cholinesterase-Inhibitoren kann aus der Literatur nicht belastbar gestützt werden. Zu Benzodiazepinen wird außer zur Behandlung von Entzugsdelirien eher nicht geraten. Präparate mit kurzer Halbwertszeit und fehlenden aktiven Metaboliten können jedoch kurzzeitig flankierend eingesetzt werden. Besonders wichtig erscheint die Prävention, zu der gute Kenntnisse der Risikofaktoren und ihres Managements beim behandelnden Personal von zentraler Bedeutung sind. Als Sonderfall erscheint das Auftreten eines Delirs im Rahmen von alpha-Synukleinopathien. Internationale und deutsche Richtlinien zum Management des Delirs existieren.
ABSTRACT Background: Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD. Methods: This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate–severe AD 441). To compare variables across groups ANOVA or χ 2 -test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS. Results: The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate–severe AD. We labelled the subgroups “depression,” “agitation,” “psychosis,” and “elation.” Conclusions: The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.
Elderly patients show us unfolded lives with unique individual characteristics. An increasing life span is associated with increasing physical and mental disease burden. Alzheimer’s disease (AD) is an increasing challenge in old age. AD cannot be cured but it can be treated. The complexity of old age and AD offer targets for personalized medicine (PM). Targets for stratification of patients, detection of patients at risk for AD or for future targeted therapy are plentiful and can be found in several omic-levels.
Depressive Störungen und demenzielle Erkrankungen treten ab dem 65. Lebensjahr einzeln und zusammen gehäuft auf. Ziel dieser Übersicht ist es, anhand einer systematischen Literaturrecherche eine Reihe von Hypothesen zu diskutieren, die dieses überzufällig häufige, gemeinsame Auftreten erklären sollen. Eine Anzahl von Untersuchungen weist auf biologische Gemeinsamkeiten zwischen Depression und Demenz hin, ohne dass diese in allen Studien untermauert werden können. Die Vorgeschichte einer Depression kann als distaler Risikofaktor für demenzielle Erkrankungen angesehen werden. Besonders nach Ausbruch demenzieller Erkrankungen sind depressive Störungen häufig und der Zusammenhang zwischen beiden wahrscheinlich am stärksten. Bei Patienten mit großer kognitiver Reserve kann eine Depression als Reaktion auf die Wahrnehmung der beginnenden kognitiven Defizite gedeutet werden. Sicherlich können Depressionen bei der Alzheimer-Demenz und anderen Demenzformen als eigene Krankheitsentität angesehen werden, zumal sich die klinischen Syndrome von denen anderer Depressionen in früheren Lebensabschnitten etwas unterscheiden. Studien über die Therapie von Depressionen bei Demenzen haben in den letzten Jahren ein steigendes Interesse gefunden. Dabei müssen jedoch bei der Behandlung älterer Patienten mit Antidepressiva einige Regeln beachtet werden, besonders kardiologische und vegetative Nebenwirkungen.
Neuropsychiatric symptoms (NPS) are increasingly being recognized as clinical markers for incipient dementia in Alzheimer's disease (AD dementia). NPS may reinforce cognitive impairment or decline and vice versa. Although NPS are frequent already in mild cognitive impairment, their mechanisms are poorly understood. It is unclear if they share biological mechanisms with cognitive symptoms and how they are associated to structural brain changes, but evidence suggests associations of NPS to cerebral atrophy. An additional NPS dimension in AD dementia concepts might add valuable information to detect patients at risk for AD dementia.
