[Evaluation of the public health measures introduced during the coronavirus pandemic: Evidence-based risk communication must be a central topic]. / Aufarbeitung der Corona-Pandemiemaßnahmen - Evidenzbasierte Risikokommunikation muss ein zentrales Thema sein.

Evidence-based and comprehensible health information is a key element of evidence-based medicine and public health. The goal is informed decision-making based on realistic estimations of health risks and accurate expectations about benefits and harms of interventions. In Germany, standards of evidence-based risk information were poorly followed during the COVID-19 pandemic. Frequently, public information was biased, fragmentary and misleading. Pandemic-related threat scenarios induced emotional distress and unnecessary anxiety. A systematic and comprehensive evaluation of the pandemic measures is crucial, but still pending in Germany. A critical analysis of risk communication by experts, politicians and the media during the pandemic should be a key element of the evaluation process. Evaluation of decision making and media reporting during the pandemic should improve preparedness for future crises.

Cochlear implant therapy improves the quality of life and social participation in the elderly: a prospective long-term evaluation.

PURPOSE: In recent years, the number of elderly cochlear implant (CI) candidates is continuously rising. In addition to the audiological improvement, other positive effects of CI treatment can also be observed in clinical routine. The "quality of life" as a parameter of success directly experienced by the patient is increasingly becoming the focus of clinical research. Although there are already clear indications of a rapid and significant improvement in quality of life, there is still a lack of systematic, prospectively collected longitudinal long-term data in patients over the age of 65. METHODS: This prospective longitudinal observational study included 31 patients between the age of 71 and 92 years who had first been treated unilaterally with a CI 6 years ago. In addition to free-field monosyllable recognition, quality of life was assessed using the World Health Organization Quality-of-Life Scale-old (WHOQL-OLD). The results were compared with the data from our previous study, in which we focused on the short- and medium-term effects on quality of life. In both studies, the same patient population was examined. In addition, these study data were compared with an age-matched average population. RESULTS: In speech recognition, there was no significant change from the control 6 months postoperatively compared with the results 6 years postoperatively. No significant changes occurred in the total quality of life score or any of the other six facets of quality of life when comparing the results 6 months postoperatively with the results 6 years postoperatively. In "Social participation", the CI patients even exceed the values of the age-matched average population 6 years after treatment. CONCLUSION: Improvement in the quality of life and especially in social participation appears stable over many years in elderly patients after hearing rehabilitation with a CI.

Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors.

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.

Compliance with CBT referral in nursing home residents diagnosed with depression: Results from a feasibility study.

Objectives: Patient-level factors that influence compliance with a recommendation for CBT in nursing home residents diagnosed with depression were identified. Methods: Within a cluster-randomized trial on stepped care for depression in nursing homes (DAVOS-study, Trial registration: DRKS00015686), participants received an intake interview administered by a licensed psychotherapist. If psychotherapy was required, patients were offered a referral for CBT. Sociodemographic characteristics, severity of depression, loneliness, physical health, antidepressant medication, prior experience with psychotherapy, and attitudes towards own aging were assessed. A binary regression determined predictors of compliance with referral. Results: Of 123 residents receiving an intake interview, 80 were recommended a CBT. Forty-seven patients (58.8 %) followed the recommendation. The binary logistic regression model on compliance with recommended CBT was significant, χ2(9) = 21.64, p = .010. Significant predictors were age (Odds Ratio (OR) = 0.9; 95 % Confidence Interval (CI) = 0.82, 0.99; p = .024) and depression (OR = 1.33; 95 % CI = 1.08, 1.65; p = .008). Conclusion: Within the implemented setting compliance rate was comparable to other age groups. Future interventions should include detailed psychoeducation on the benefits of psychotherapy on mild depressive symptoms in older age and evidence-based interventions to address the stigma of depression. Interventions such as reminiscence-based methods or problem-solving could be useful to increase compliance with referral, especially in very old patients (80+). Language barriers and a culturally sensitive approach should be considered when screening residents.

[Strengthening prevention and health promotion in and for old age]. / Prävention und Gesundheitsförderung im und für das Alter stärken.

BACKGROUND: Disease prevention and health promotion in and for old age have become increasingly more important. Nevertheless, more (national) research and implementation in practice is needed, as the international comparison shows. OBJECTIVE: To develop guiding principles for research and practice on prevention and health promotion in and for old age. MATERIAL AND METHODS: As part of an iterative process, members of the German Society of Gerontology and Geriatrics came together in workshops and symposia to formulate key guiding principles and fields of action for prevention and health promotion. RESULTS: The following were worked out: 1) prevention and health promotion are useful and possible up to oldest age, 2) prevention and health promotion for advanced age should start early, 3) prevention and health promotion must take into account the diversity and heterogeneity of the life situations of old people, 4) prevention and health promotion promote and demand self-determination and participation, 5) prevention of multiple illnesses must be given greater attention, 6) prevention of the need for long-term care and prevention in long-term care must be treated equally, 7) prevention and health promotion must be thought of in terms of life worlds and across sectors, paying particular attention to aspects of social inequality and a focus on resources, 8) prevention and health promotion and the related research must be interdisciplinary and transdisciplinary and be applied at different levels, from molecular to societal. DISCUSSION: The guiding principles outline the focal points of future-oriented ageing, health and healthcare research and open up fields of action but also show the limits of this approach for political decision-makers, researchers and practitioners.

Effectiveness of exercise interventions to improve long-term outcomes in people living with mild cognitive impairment: a systematic review and meta-analysis.

Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically. The aim was to assess (1) the effectiveness of exercise and physical activity (EXPA) interventions in improving long-term patient-relevant cognitive and non-cognitive outcomes in people with mild cognitive impairment, (2) how well the included trials reported details of the intervention, and (3) the extent to which reported endpoints were in line with patient preferences that were assessed in patient workshops. Following PRISMA guidelines, we performed a systematic review and meta-analysis including randomized controlled trials. A total of ten studies were included after searching in six electronic sources from 1995 onwards. There is a trend that 6 + -month EXPA interventions improve global cognition 12 months after initiation. Evidence on long-term effects of EXPA interventions on non-cognitive health outcomes could not be meaningfully pooled and the individual studies reported mixed results. Workshop participants considered freedom from pain and stress, mood, motivation and self-efficacy to be important, but these outcomes were rarely addressed. Too little information is available on intervention details for EXPA programs to be replicated and confidently recommended for patients with MCI. PROSPERO registration in December, 2021 (CRD42021287166).

[Non-pharmacological Therapies of Dementia - an Update]. / Nicht pharmakologische Therapien bei Demenz.

Non-pharmacological Therapies of Dementia - an Update Abstract: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. This is an up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use according to the current state of research and the recommendations of AWMF S3 guideline "dementia". The most important interventions from this therapeutic spectrum are cognitive stimulation to maintain cognitive functioning, physical activation, and creative therapeutic offers to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

[Non-pharmacological interventions for people with dementia]. / Nichtmedikamentöse Interventionen für Menschen mit Demenz.

BACKGROUND: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. OBJECTIVE: An up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use. MATERIAL AND METHODS: Narrative review taking into account the current state of research and the recommendations of the Working Group of (German) Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) S3 guideline "Dementia". RESULTS AND CONCLUSIONS: The most important interventions from this therapeutic spectrum include cognitive stimulation to maintain cognitive functioning, physical activation and creative therapeutic activities to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

[Mild cognitive impairment in geriatric practice: patient orientation, diagnostics, treatment and ethics]. / Leichte kognitive Beeinträchtigung (MCI) in der altersmedizinischen Praxis: Patientenorientierung, Diagnostik, Behandlung und Ethik.

Mild cognitive impairment (MCI) is a common problem in old people, which can be distressing for patients and their families. The main feature of MCI is a decrease in cognitive performance with activities of daily living still unimpaired. The identification of treatable risk factors, recognition of early cognitive changes and a timely differential diagnosis, comprehensive information and counselling are important tasks in geriatric medicine. The aim of this article is to present practical recommendations to support physicians working with geriatric patients in recognizing cognitive deficits at an early stage, provide high-quality care focusing on counselling, treatment, and comorbidity management and to maximize the potential of the available treatment options.

Empowering patients with dementia to make legally effective decisions: a randomized controlled trial on enhancing capacity to consent to treatment.

Objectives: As our society ages, the incidence of age-related diseases increases and with it the number of medical treatments that require informed consent. Capacity to consent is often categorically questioned in persons with dementia (PwD) without appropriate assessment, depriving them of their right to autonomous decision-making. Supportive structures for PwD that comply with legal requirements are lacking. The EmMa project tried to overcome this shortcoming by developing and testing possible supportive measures to enhance the informed consent process for PwD.Method: These enhanced consent procedures (ECPs) were tested in a randomized controlled trial with 40 PwD. It was hypothesized that strengths-based ECPs could improve capacity to consent to a drug treatment in PwD as measured with a semi-structured interview.Results: Against the expectations, no effect of the ECPs on capacity to consent could be found, but the ECPs improved understanding of information in PwD.Conclusion: To empower PwD in clinical settings, however, all aspects of capacity to consent should be targeted with specific aids that are implemented carefully and selectively. More research on possible aids for ECPs is urgently needed in order to enable ethically and legally robust informed consent. In particular, effective ways to improve both reasoning and appreciation are yet to be found.

Effectiveness of exercise and physical activity interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with mild cognitive impairment: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Mild cognitive impairment (MCI) is a clinical syndrome characterised by persistent cognitive deficits that do not yet fulfil the criteria of dementia. Delaying the onset of dementia using secondary preventive measures such as physical activity and exercise can be a safe way of reducing the risk of further cognitive decline and maintaining independence and improving quality of life. The aim is to systematically review the literature to assess the effectiveness of physical activity and exercise interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with MCI, including meta-analyses if applicable. METHODS AND ANALYSIS: We will systematically search five electronic databases from 1995 onward to identify trials reporting on the effectiveness of physical activity and exercise interventions to improve long-term (12+ months) patient-relevant cognitive and non-cognitive outcomes in adults (50+ years) with MCI. Screening procedures, selection of eligible full-texts, data extraction and risk of bias assessment will be performed in dual-review mode. Additionally, the reporting quality of the exercise interventions will be assessed using the Consensus on Exercise Reporting Template. A quantitative synthesis will only be conducted if studies are homogeneous enough for effect sizes to be pooled. Where quantitative analysis is not applicable, data will be represented in a tabular form and synthesised narratively. People living with MCI will be involved in defining outcome measures most relevant to them in order to assess in how far randomised controlled trials report endpoints that matter to those concerned. ETHICS AND DISSEMINATION: Results will be disseminated to both scientific and lay audiences by creating a patient-friendly video abstract. This work will inform professionals in primary care about the effectiveness of physical activity and exercise interventions and support them to make evidence-based exercise recommendations for the secondary prevention of dementia in people living with MCI. No ethical approval required. PROSPERO REGISTRATION NUMBER: CRD42021287166.

Investigating the Association Between Polygenic Risk Scores for Alzheimer's Disease With Cognitive Performance and Intrinsic Functional Connectivity in Healthy Adults.

Background: Alzheimer's disease (AD) pathology is present many years before the onset of clinical symptoms. AD dementia cannot be treated. Timely and early detection of people at risk of developing AD is key for primary and secondary prevention. Moreover, understanding the underlying pathology that is present in the earliest stages of AD, and the genetic predisposition to that might contribute to the development of targeted disease-modifying treatments. Objectives: In this study, we aimed to explore whether genetic disposition to AD in asymptomatic individuals is associated with altered intrinsic functional connectivity as well as cognitive performance on neuropsychological tests. Methods: We examined 136 cognitively healthy adults (old group: mean age = 69.32, SD = 4.23; young group: mean age = 31.34, SD = 13.12). All participants had undergone resting-state functional magnetic resonance imagining (fMRI), DNA genotyping to ascertain polygenic risk scores (PRS), and neuropsychological testing for global cognition, working memory, verbal fluency, and executive functions. Results: Two-step hierarchical regression analysis revealed that higher PRS was significantly associated with lower scores in working memory tasks [Letter Number Span: ΔR 2 = 0.077 (p < 0.05); Spatial Span: ΔR 2 = 0.072 (p < 0.05)] in older adults (>60 years). PRS did not show significant modulations of the intrinsic functional connectivity of the posterior cingulate cortex (PCC) with other regions of interest in the brain that are affected in AD. Conclusion: Allele polymorphisms may modify the effect of other AD risk factors. This potential modulation warrants further investigations, particularly in cognitively healthy adults.

Long-term effects on the quality of life following cochlear implant treatment in older patients.

PURPOSE: Even in older patients, hearing rehabilitation with a cochlear implant has become an established method for deafened or severely hearing-impaired patients. In addition to the hearing improvement, numerous other effects of CI treatment can be observed in clinical routine. In the literature, there is multiple evidence for a rapid and significant improvement in quality of life with CI treatment. The aim of this study was to evaluate the long-term effects of hearing rehabilitation using CI on the quality of life in older patients (≥ 65 years). METHODS: This prospective cross-sectional study examined 84 patients between the age of 65 and 101 years who received unilateral CI treatment for the first time between one and 10 years ago. The World Health Organization Quality-of-Life Scale-Old (WHOQL-OLD) was used to determine the quality of life. The study cohort was divided into three groups to compare the quality of life over time: group I (1-3 years after CI treatment), group II (4-6 years after CI treatment), and group III (7-10 years after CI treatment). In addition, the data from this study were compared with the results of our previous study (Issing et al. 2020) in which we focused on the first 6 months after CI treatment. RESULTS: In all three groups, there was a significant improvement in monosyllabic discrimination within 1 year after CI fitting (p > 0.001). No significant differences were found between the three groups. There were no significant differences between the three groups in the WHOQOL-OLD total score (p = 0.487) or any of the other six facets. Moreover, no significant differences were found compared to the study group of our previous study 6 months after CI treatment. CONCLUSION: This study demonstrates the long-term stability of the improved quality of life following unilateral CI treatment in patients aged 65 years or older.

[Non-pharmacological interventions in dementia: an overview with special consideration of digital offerings]. / Nichtpharmakologische Interventionen bei Demenz.

Non-pharmacological interventions such as cognitive therapy, physical activity, and creative art approaches are important components of appropriate care for persons with dementia and their relatives. Although relationships and interpersonal interactions undoubtedly play an important role in all these activities, digital technologies have increasingly established themselves in this area in recent years. The following article describes non-pharmacological interventions for people with dementia (based on the German AWMF S3 dementia guideline), and additionally provides examples of selected digital approaches for this particular target group. As the aim of the interventions is to support persons with dementia in living autonomously and maintaining societal and cultural participation, all the interventions share a consideration for individual resources and the promotion of available potential. Empirical evidence on digital activities remains scarce, so it is not yet possible to make clear recommendations. When using them, it should therefore be borne in mind that although they may represent a valuable supplement, they can never replace human attention. Furthermore, limitations in their practical application, such as unfamiliarity when using digital technologies or excessive demands of cognitively limited users, as well as important ethical aspects (e. g., data protections, personality rights, dignity and self-determination in old age) should not be ignored.

Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network.

ApoE4, the strongest genetic risk factor for Alzheimer's disease (AD), has been shown to be associated with both beta-amyloid (Aß) and tau pathology, with the strongest evidence for effects on Aß, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF Aß42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF Aß42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF Aß42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF Aß 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and Aß42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-ß burden and tau aggregation at specific time points in AD pathogenesis.

Person-environment fit of environmental support provided during medical consultations with older patients.

As some cognitive functions decline in old age, the ability to decide about important life events such as medical treatment is endangered. Environmental support to improve the comprehension of health-related information is therefore necessary. With a small-scale explorative approach, the present survey study aimed at investigating person-environment fit (PE-fit) of support provided during medical consultations. This fit was calculated by assessing the match between aids provided by five medical practitioners during medical consultations and aids most appreciated by the geriatric patients (N = 88). The results showed that the largest discrepancies of used and appreciated aids could be found concerning the opportunity to discuss decisions with relatives, the possibility to take notes, the use of objects, pictures and a keyword list. Female patients indicated a lower PE-fit. These findings highlight discrepancies between the use of specific aids and the wishes of patients and call for thoughtful use of aids during consultations with geriatric patients.

Supported Decision-Making in Persons With Dementia: Development of an Enhanced Consent Procedure for Lumbar Puncture.

The right to make autonomous decisions is enshrined in law. However, the question how persons with cognitive deficits can be enabled to make autonomous decisions has not been satisfactorily addressed. In particular, the concept of supported decision-making and its implementation into practice has been poorly explored for persons with dementia (PwD).This article describes the empirical development and implementation of support tools to enhance informed consent processes (so called enhanced consent procedures/ECP) for PwD on whether to undergo lumbar puncture. In the end of the process of pilot testing and further development of the tools, the following tools were defined: (1) Standardized Interview Structure, (2) Elaborated Plain Language, (3) Ambience and Room Design, (4) Keyword Lists, (5) Priority Cards, (6) Visualization, and (7) Simplified Written Informed Consent (Patient Information), as well as the general attitude (8) Person-Centered Attitude of the facilitator. As the development, implementation and evaluation of ECP tools is one objective of the transnational ENSURE project, we also include an overview of future empirical procedures. So far, our findings can serve as a selection of possibilities to support PwD in decision-making and help practitioners achieve an appropriate balance between the autonomy and protection of PwD in complex decision-making situation. Future studies should address the question if the proposed set of tools is effective to enhance informed consent processes in PwD.

Neural Correlates of Autobiographical Memory: Evidence From a Positron Emission Tomography Study in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Background: Autobiographical memory (AM) changes are the hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI). In recent neuroimaging studies, AM changes have been associated with numerous cerebral sites, such as the frontal cortices, the mesial temporal lobe, or the posterior cingulum. Regional glucose uptake in these sites was investigated for underlying subdimensions using factor analysis. Subsequently, the factors were examined with respect to AM performance in a subgroup of patients. Methods: Data from 109 memory clinic referrals, who presented with MCI (n = 60), mild AD (n = 49), or were cognitively intact, were analyzed. The glucose metabolic rates determined by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in 34 cerebral sites important for AM were investigated for underlying subdimensions by calculating factor analysis with varimax rotation. Subsequently, the respective factor scores were correlated with the episodic and semantic AM performance of 22 patients, which was measured with a semi-structured interview assessing episodic memories (characterized by event-related emotional, sensory, contextual, and spatial-temporal details) and personal semantic knowledge from three periods of life (primary school, early adulthood, and recent years). Results: Factor analysis identified seven factors explaining 69% of the variance. While patients with MCI and AD showed lower values than controls on the factors frontal cortex, mesial temporal substructures, and occipital cortex, patients with MCI presented with increased values on the factors posterior cingulum and left temporo-prefrontal areas. The factors anterior cingulum and right temporal cortex showed only minor, non-significant group differences. Solely, the factor mesial temporal substructures was significantly correlated with both episodic memories (r = 0.424, p < 0.05) and personal semantic knowledge (r = 0.547, p < 0.01) in patients with MCI/AD. Conclusions: The factor structure identified corresponds by large to the morphological and functional interrelations of the respective sites. While reduced glucose uptake on the factors frontal cortex, mesial temporal substructures, and occipital cortex in the patient group may correspond to neurodegenerative changes, increased values on the factors posterior cingulum and left temporo-prefrontal areas in MCI may result from compensatory efforts. Interestingly, changes of the mesial temporal substructures were correlated with both semantic and episodic AM. Our findings suggest that AM deficits do not only reflect neurodegenerative changes but also refer to compensatory mechanisms as they involve both quantitative losses of specific memories and qualitative changes with a semantization of memories.