I answer this question thinking more about what they want to ask than what they are really asking. There is heterogeneity in the development of Alzheimer's disease symptoms. There are behavioral variants, but in the MIR they usually want you to think of other types of dementias in the face of behavioral symptoms. In fact, the appearance of these symptoms in early stages should alert us and open the range of diagnostic possibilities. Therefore, we discard 2 and 4. Between 1 and 3, I choose 3 for the same reason and because of the emphasis on the decline of functional independence that occurs in these patients.

I answer this question thinking more about what they want to ask than what they are really asking. There is heterogeneity in the development of Alzheimer's disease symptoms. There are behavioral variants, but in the MIR they usually want you to think of other types of dementias in the face of behavioral symptoms. In fact, the appearance of these symptoms in early stages should alert us and open the range of diagnostic possibilities. Therefore, we [HIDDEN] Between 1 and 3, I [HIDDEN] for the same reason and because of the emphasis on the decline of functional independence that occurs in these patients.

A 75-year-old woman brought for consultation by her family because they have been finding her depressed and with memory lapses for months. They are concerned that she may have Alzheimer's disease. The patient refers that she does not think anything is wrong with her and that she is as usual. In what order do the following symptoms generally occur in the progression of Alzheimer's disease:

Mood changes, behavioral symptoms, cognitive deficits.

Behavioral symptoms, motor symptoms, decline of functional independence.

Mood changes, cognitive deficit, decline of functional independence.

Behavioral symptoms, mood changes, motor symptoms.

Behavioral neuroscience

Parkinson's disease, a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech. Huntington's disease, a rare inherited neurological disorder whose most obvious symptoms are abnormal body movements and a lack of coordination. It also affects a number of mental abilities and some aspects of personality. Alzheimer's disease, a neurodegenerative disease that, in its most common form, is found in people over the age of 65 and is characterized by progressive cognitive deterioration, together with declining activities of daily living and by neuropsychiatric symptoms or behavioral changes. Clinical depression, a common psychiatric disorder, characterized by a persistent lowering of mood, loss of interest in usual activities and diminished ability to experience pleasure.

Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Noncognitive disturbances in Alzheimer's disease: frequency, longitudinal course, and relationship to cognitive symptoms.

To investigate the frequency and longitudinal course of symptoms of depression, agitation, and psychosis in a longitudinally studied sample of patients with Alzheimer's disease (AD). Longitudinal study of AD patients with follow-up assessments at 6-month intervals for an average of more than 3 years. Alzheimer's Disease Research Center of the Mount Sinai Medical Center and the Bronx VA Medical Center, New York. A total of 153 AD patients. Blessed Test of Information, Memory and Concentration (BIMC) and the Alzheimer's Disease Assessment Scale cognitive (ADAS-Cog) and noncognitive (ADAS-NC) subscales. At entry into the study, more than 90% of patients had a behavioral disturbance that was rated as mild or worse on one of the 10 ADAS noncognitive items; and 40% had at least one rating that was moderate or severe. Correlational analyses indicated that, with the exception of the two mood-related items, noncognitive symptoms on the ADAS were not highly correlated with one another. Only one of the noncognitive items, concentration, was strongly correlated with the severity of cognitive impairment. On average, patients showed progressively worse cognitive functioning over time as measured both by the ADAS-Cog and the BIMC. The mean severity of noncognitive symptoms did not change during the course of a 5-year follow up. The severity of behavioral disturbance at any one evaluation was negatively correlated with change in behavior during the next 6 months and was not correlated with cognitive decline. Mild behavioral disturbances are common, whereas moderate to severe behavioral symptoms are less frequent in this population of AD patients. Disturbances in mood and manifestations of agitation and psychotic symptoms are not closely related to one another and show little progressive worsening over time. Rather, they tend to be episodic such that increasing severity at one time is usually followed by improvement later. Concentration problems are a manifestation of cognitive dysfunction rather than behavioral disturbance in AD. Implications of these results for treatment of noncognitive disturbances in AD are discussed.

Dementia

Dementia manifests as a set of related symptoms, which usually surface when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively impact a person's ability to function and carry out everyday activities. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Consciousness is not affected. Dementia ultimately has a significant effect on the individual, caregivers, and relationships in general. A diagnosis of dementia requires a change from a person's usual mental functioning and a greater cognitive decline than what is caused by normal aging. Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most common cause is Alzheimer's disease, a neurodegenerative

Neuron

Alzheimer's disease (AD), also known simply as Alzheimer's, is a neurodegenerative disease characterized by progressive cognitive deterioration, together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is loss of short-term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), and recognition (agnosia), and functions such as decision-making and planning become impaired.

[A longitudinal study of the course of Alzheimer type dementia].

We carried out a prospective longitudinal study of 41 patients diagnosed as probably having a mild form of Alzheimer's disease according to the data of an investigation of prevalence done in 1991 in the municipality of Habana Vieja. The research covered two phases, with an interval of one year between them. During both phases the patients were interviewed by the same neurology resident in a door-to-door survey using the Mini-Mental State, Hughes scale (CDR) and Blessed scale, to evaluate higher mental functions. We determined the progress of the disease over the course of two years (1991-1992 and 1992-1993) and the frequency and degree of deterioration of cognitive functions during a period of one year. There was evidence of progressive worsening of the illness in 46.4% of the patients. In 34.2% this was to a moderate form and in 12.2% to a severe form. There was no progression in 46.3%. In this group 17.0% continued with a diagnosis of doubtful dementia and 29.3% as having slight dementia. The other 7.3% of the total number of patients (n = 41) were reclassified as normal. Cognitive functions almost always showed a tendency to deteriorate over time, but in a small percentage of patients they did not deteriorate and some even improved. The cognitive functions which deteriorated most were those of orientation, language and copying, with an average deterioration of 28% and 24% respectively with regard to their initial values.

Report of ten years' activity in an Alzheimer's disease assessment unit.

After ten years' treatment with cholinesterase inhibitors (AcheI) in Alzheimer's disease (AD), we report here the activity of the Alzheimer's Disease Assessment Unit of IRCCS C. Mondino, Pavia, Italy. From September 2000 to December 2007, 794 out-patients (of 2236 referred to our Assessment Unit for cognitive disturbances) with AD of mild to moderate degree were treated with cholinesterase inhibitors (M/F: 273/521, mean age 73.6+/- 8.4 yrs, range 52-85 yrs). Outcome measures were scores on Mini Mental State Examination (MMSE), ADL, IADL and Neuropsychiatric Inventory (NPI). Mean treatment duration was 36.9+/-16.1 months. After three months' treatment, MMSE scores remained stable (responders) in 60% of cases and improved (increase of 3 or more points - good responders) in 15%, with good preservation of autonomy. After 15 months, the percentage of "good responders" decreased to 7%, while after 15, 27 and 39 months the percentage of responders progressively decreased to 40%, 30% and 8%, respectively; greater impairment in instrumental with respect to basic everyday activities was noted. No variables capable of predicting the response to treatment were detected. The onset of behavioral disturbances caused significant (p<0.02) worsening of both cognition and function and, in 12% of cases, suspension of treatment. Our results therefore confirm the efficacy of AcheI in AD of mild to moderate degree even in a nonselected population; efficacy also seems to persist in long-term treatment. This report, although brief and mainly descriptive, can make a contribution to better knowledge of the usefulness of these drugs in AD of mild to moderate extent in everyday clinical practice.

The influences of psychotic symptoms on the activities of daily living of individuals with Alzheimer disease: a longitudinal analysis.

Psychotic symptoms associated with Alzheimer Disease (AD) contribute to excess functional dependence. Longitudinal studies have generally examined the association between rates of functional decline and the occurrence of psychotic symptoms from either a single evaluation or from multiple evaluations rather than through changes in frequency and severity of symptoms. Although the presence or absence of psychotic symptoms at initial or follow-up examinations may be associated with changes in functional status, the nature of the relationship between changes in these domains cannot be inferred. We examine the association between changes in the frequency of psychotic symptoms and changes in dependence in activities of daily living (ADL) over a period ranging from 1 to 74 months (median = 17.7). Data from a cohort of 234 individuals referred to a memory clinic were analyzed using multilevel linear regression. Information on ADL, behavioral and psychological symptoms, depression, and cognition was collected. An increase in the frequency of psychotic symptoms had a unique influence on the deterioration of basic ADL, after controlling for demographic variables, changes in cognition, depression, and other behavioral and psychological symptoms (B = -.017, p = .003). However, changes in psychotic symptoms did not significantly contribute to declines in the ability to perform instrumental ADL (B = -.008, p = .439). Changes in psychotic symptoms may influence basic but not instrumental ADL over time. These findings may have ramifications for studies and treatment plans for individuals with AD who demonstrate psychotic symptoms.

Variably protease-sensitive prionopathy

Patients present with behavioral and psychiatric symptoms, speech deficits (aphasia and/or dysarthria) and progressive cognitive and motor decline (dementia, ataxia, parkinsonism, psychosis, aphasia and mood disorder). Average age at onset is 70 years, and duration of survival is 24 months. About 40% of patients have a family history of dementia. Like CJD, it can be mistaken for Alzheimer's dementia.

[Clinical aspects and course of Alzheimer's disease].

The diagnosis of Alzheimer's disease must be considered in all subjects over 40 years of age whose mental functions have insidiously become altered and are progressively getting worse. The initial phase of the disease, which precedes dementia, is characterized by disorders of memory often associated with changes in personality and behaviour and with subtle disorders of speech, reasoning and abstraction ability and visuo-constructive capabilities. The results of neurological and paraclinical examinations are normal. This phase lasts from two to four years and may be diagnosed as "possible Alzheimer's disease". When the disease is established the patient has lost his autonomy and can only be kept at home with the help of his relatives. Dementia gradually becomes worse, with a combination of memory disturbance, aphasia-apraxia-agnosia syndrome, impaired intellectual faculties and disorders of behaviour. Computerized tomography shows evidence of cerebral atrophy. This phase lasts from three to six years and may be called "probable Alzheimer's disease". The terminal phase of the disease includes somatic lesions, and all mental functions are profoundly altered. Death occurs seven to ten years after the first symptoms. Histopathological data are necessary to make a diagnosis of "confirmed Alzheimer's disease", since there is no clinical, morphological, electrophysiological or radiological sign that is pathognomonic of that disease.

Huntington's disease

Signs and symptoms Signs and symptoms of Huntington's disease most commonly become noticeable between the ages of 30 and 50 years, but they can begin at any age, and present as a triad of motor, cognitive, and psychiatric symptoms. In 50% of cases, the psychiatric symptoms appear first. Their progression is often described in early stages, middle stages, and late stages with an earlier prodromal phase. In the early stages, subtle personality changes, problems in cognition, and physical skills, irritability, and mood swings occur, all of which may go unnoticed, and these usually precede the motor symptoms. Almost everyone with HD eventually exhibits similar physical symptoms, but the onset, progression, and extent of cognitive and behavioral symptoms vary significantly between individuals.

Change in the mini-mental state exam in Alzheimer's disease over 2 years: the experience of a dementia clinic.

The decline in the Mini-Mental State Exam (MMSE) over 2 years was assessed in males with Alzheimer's disease (AD; N = 136) seen in a dementia clinic. The average initial MMSE was 21.0 (SD+/-3.9; range 14--29) and declined 2.8 points (+/-4.7; range -17 to +6) over 2 years. The mode for change on the MMSE was 0 (N = 22) while the median fell between 2 and 3 points lost. Fifty-five of 136 patients (39.7%) had unchanged or better scores. There was no significant correlation between the initial MMSE and rate of change (r = -0.16; p = 0.06). While the progression of AD is quite variable from patient to patient, our data indicate that in most it is associated with little if any change in the MMSE even over 2 years. The MMSE is not an adequate tool to monitor change in the individual patient with AD.

Frontotemporal dementia

The confusion between Alzheimer's and FTD is justifiable due to the similarities between their initial symptoms. Patients do not have difficulty with movement and other motor tasks. As FTD symptoms appear, it is difficult to differentiate between a diagnosis of Alzheimer's disease and FTD. There are distinct differences in the behavioral and emotional symptoms of the two dementias, notably, the blunting of emotions seen in FTD patients. In the early stages of FTD, anxiety and depression are common, which may result in an ambiguous diagnosis. However, over time, these ambiguities fade away as this dementia progresses and defining symptoms of apathy, unique to FTD, start to appear.

[Rates of progression in mild cognitive impairment].

The aim of the study which was based on a five year prospective scheme was the evaluation of progressive changes in persons with a diagnosed mild cognitive impairment (MCI). A result of 3 in the Global Deterioration Scale (Reisberg's criteria), allowed for mild cognitive impairment diagnosis. The CGI scale result in the 5th year of observation was the bases to divide the studied population into a group with a stable MCI course and a group with progressive symptoms. 41 persons finished the five years of observation, out of a total 46 chosen for the study. After 5 years, 26 persons had no changes in the CGI result, whilst 15 persons showed a worsening in their clinical picture. At the initial qualification to the study the two groups of patients did not differ in their psychiatric state. However differences in the ADAS-kog could be seen in the second measurement done after the first year of the observation. Amongst those persons who had a worsening above 1.68 in the first year of the observation, Alzheimer's disease could be diagnosed definitely more frequently in the further stages of the observation. Evaluation of cognitive function impairment progression seems to be one of the most important diagnostic elements and should be included in the diagnostic criteria of MCI.

Late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of dementia: a case report.

Although adult attention-deficit/hyperactivity disorder has recently gained increased attention, few reports on attention-deficit/hyperactivity disorder in the pre-elderly or elderly have been published. Here, we present the case of a patient with attention-deficit/hyperactivity disorder who gradually developed dementia-like symptoms as she aged, which initially made her condition difficult to distinguish from early onset Alzheimer's disease. This report illustrates that some types of attention-deficit/hyperactivity disorder may be misdiagnosed as dementia. The patient was a 58-year-old woman. Although she presented with a tendency for inattentiveness and forgetfulness since childhood, she did not have a history of psychiatric disorders prior to consultation. Around the age of 52 years, her inattentiveness and forgetfulness gradually progressed, and at 57 years of age, she became inattentive and forgetful that it interfered with her work and daily life. For example, she forgot meetings with important clients and transferred money to the wrong bank account; these failures resulted in poor management of her company. At home, she experienced increasing difficulties with remembering prior commitments with her family and misplacing items, which her family members noticed. With the encouragement of her family and employees, who worried that she was suffering from dementia, she visited our memory clinic, whereby she was suspected of having early onset Alzheimer's disease. However, neuropsychological tests and brain imaging evaluations did not reveal any significant abnormalities. After dismissing various possible diagnoses, including dementia, other organic diseases, mood disorders, and delirium, we diagnosed her with attention-deficit/hyperactivity disorder. Treatment with 18 mg of methylphenidate was initiated, and significant improvements in her symptoms were observed within a few days; for example, she stopped losing her things, was able to concentrate for long durations, and could complete more tasks than she could before treatment. Since initiating treatment, she has returned to work and has been able to perform her daily activities without difficulty. This case supports that some patients with late-onset attention-deficit/hyperactivity disorder may gradually develop dementia-like symptoms during the pre-elderly and elderly stages of life. Therefore, clinicians should consider late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of some types of dementias.

Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline.

We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimer's disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills.

Letter to the Editor: Depression As The First Symptom Of Frontal Lobe Grade 2 Malignant Glioma.

Dear Editor, Next to focal neurological symptoms, epileptic seizures and head aches, brain tumors can less frequently bring about cognitive changes, slowed speech, difficulty sustaining mental functioning and psychiatric symptoms of personality changes and. loss of interest in daily activities, these symptoms may be evaluated as anxiety or depression. Depression is known to be a complication of brain tumours and may sometimes be seen after the presentation of neurological symptoms linked to brain tumours, and sometimes after tumor treatment (Oğuz et al. 2005, Litofsky et al. 2004, Moise and Madhusoodanan 2006, Oreskovic M et al. 2007, Rooney A et al. 2010). The dorsolateral prefrontal, orbitofrontal and medial frontal circuits constitute the three subcortical neuronal circuits in the frontal cortex. The dorsolateral prefrontal circuit is associated with planning and operational functions and lesions on it may give rise to apathy, abulia, perseveration, personality changes and planning disorder. Lesions involving the orbitofrontal circuit, which is associated with response suppression and disinhibition, may involve emotional lability and memory problems. Whereas lesions affecting the right orbitofrontal circuit give rise to elevated mood, lesions on the left orbitofrontal circuit lead to depressed mood. In cases with medial frontal circuit involvement, akinetic mutism may result from lesions in the superior medial region and anteroretrograde amnesia and confabulation are observed with lesions in the inferior medial region (Tosun et al. 2016, Chirchiglia 2018). A diagnosis of psychiatric disorder may be given during the first examination of patieants with primary brain tumours, especially if localized in the frontal lobe. Thorough history taking and physical examination are necessary for early diagnosis. The case reported here concerns a 29-year-old university graduate female patient, living with her partner and children, who consulted the clinic with complaints of tendency to frequent crying, anhedonia, having difficulty with speech fluency, forgetfulness and distractedness that had presented suddenly, 2 months previously, without any causative stressor. In her mental status examination, she appeared having normal self-care with appearance at her actual age. She was fully conscious and oriented, not willing to cooperate with the interview, had distinct difficulty in maintaining attention and with fluency of speech. Her mood was depressive. She described loss of appetite, fatigue and energy loss. Her difficulty in paying attention was pronounced. She did not have a history of psychotropic medication use or family history of psychiatric disease. She did not smoke or use alcohol or substance. After evaluating the clinical interview, a preliminary diagnosis of major depressive disorder was considered on the basis of the DSM-5 criteria. Routine blood tests were requested. Given the continuation of her complaints, the difficulty with fluent speech and the increase in tendency to sleep at the first week follow up, cranial MRI was planned. The MRI results showed on the right, in the frontal lobe a multilocular mass with precallosal extension, undiscernable margins with the right lateral aspect of the corpus callosum genu and dispersed cystic-necrotic areas with T2 signal series. The dimensions of the mass were nearly 5 x 3 cm causing a 1-cm right-to-left shift of the midline (Figure 1) DEPRESSION AS THE FIRST SYMPTOM OF FRONTAL LOBE GRADE 2 MALIGNANT GLIOMA 2 Türk Psikiyatri Dergisi 2 Turkish Journal of Psychiatry Letter to the Editor 143 144 The patient was referred for surgery with the preliminary diagnosis of high-grade glial tumour. Pathology results identified a grade 2 glioma. It was learned that radiotherapy sessions were begun after surgery. The patient did not have any symptoms of psychopathology during the 2 monthly psychiatric interviews made after surgery. Brain tumours generally indicate their presence with headache, seizures and other neurological symptoms and very rarely with depression as seen in the case of our patient. It should be kept in mind that atypical psychiatric symptoms may have an underlying organic lesion and subtle neurological symptoms should be investigated in detail. A recent meta-analysis on 37 observational studies determined a 21.7% prevalence of depression in a total of 4518 patients with intracranial tumours. Comorbidity of depression with brain tumor was demonstrated to worsen the quality of life, increase suicidal risk and lower the chance of survival (Huang et al. 2017). The possibility of psychiatric symptoms being the clinical clues for brain cancer was noted and the necessity of neuroimaging tests in cases of recent-onset psychosis or mood disorder symptoms, atypical personality changes and anorexia without body dysmorphic disorder was emphasized (Madhusoodanan et al. 2015). Loss of interest, tendency to frequent weeping, introversion and anhedonia were the sole complaints in the case discussed here. The increase in psychomotor retardation and slowing down of movements at the very first weekly control follow up necessitated neuroimaging. Despite the reports in the literature on the frequent association of unpreventable excessive behavior, disinhibition and irritability with right frontal injury and lesions (Okumuş and Hocaoğlu 2018), depression was the dominant symptom in the case presented here. There are differences between primary major depression and depression presenting with underlying somatic diseases which is known to occur at later ages (Rouchell et al. 2002). However, our patient was aged 29 years. Also, cases of depression due to somatic disease are less associated with family history of depression and suicidal ideation and attempts, while cognitive symptoms come to the foreground during mental status examination. (Sertöz and Mete 2004, Rouchell et al. 2002). Our patient did not have suicidal ideation or attempts, or a family history of depression. In apathy, which may be explained as emotional blunting, indifference or detachment from the external world, targeted behavior is also reduced next to the lack of emotional expression. The individual discussed here was learned not to sit at the table or change the television channel unless reminded to do so. When the reason was asked, she could not think of one. The reduction in emotional expression accompanies reduced insight, abulia and lack of empathy (Sözeri Varma et al. 2019). In depression, apathy is defined as 'sorrowless depression'. Our patient cried but had very blunted mimics and gestures. She explained that she could not help weeping even at times when she did not feel internally distressed. The seriousness of apathy, as a symptom difficult to differentiate from depression, is still not understood. Neuroimaging Figure 1- Cranial MRI of the patient 145 Received: 16.08.2020, Accepted: 04.12.2020, Available Online Date: 05.10.2021 1MD., Antalya Kepez State Hospital, Department of Psychiatry, Antalya, 2MD., Ordu University Training and Research Hospital, Department of Psychiatry, Ordu, Turkey e-mail: bosbora@yahoo.com https://doi.org/10.5080/u25957 studies indicate apathy to be a reflect of impaired frontal-subcortical circuits and the functional disorder of the connections between the ventromedial prefrontal cortex and the basal ganglia (Chase 2011). Comparison of 45 individuals with depression due to aging and 43 healthy individuals showed apathy to be associated with fronto-limbic gray and white matter abnormalities which continued after antidepressant treatment. The structural anomalies of the posterior subgenual cingulate gyrus and the uncinate fasciculus were discussed (Yuen 2014). The case discussed here is presented to emphasize the importance of brain imaging methods and detailed investigation of atypical symptoms for diagnostic approaches to psychiatric disorders. Especially, complaints at young age of depression with psychomotor retardation, reduced fluency of speech and sudden onset withdrawal without stressors should be a warning of secondary depression. Yours sincerely... Şerif Bora Nazlı1 , Muhammet Sevindik2 REFERENCES Chase TN (2011) Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment. Neurotox Res 19:266-78. Chirchiglia D (2018) Pseudodepression as an Anticipatory Symptom of Frontal Lobe Brain Tumors. Int J Depress Anxiety 1:007. Huang J, Zeng C, Xiao J et al (2017) Association between depression and brain tumor: a systematic review and meta-analysis. Oncotarget 8:94932-43. Litofsky NS, Farace E, Anderson F et al (2004) Depression in patients with high-grade glioma: Results of the glioma outcomes project. Neurosurgery 54:358-67. Madhusoodanan S, Ting MB, Farah T et al (2015) Pyschiatric aspects of brain tumors: A review. World J Psychiatry 5:273-85. Moise D, Madhusoodanan S (2006) Psychiatric symptoms associated with brain tumors: a clinical enigma. CNS Spectr 2006;11:28-31. Oğuz N, Ilnem C, Yener F (2005) Psychiatric symptoms in brain tumors: Case reports. Bulletin of Clinical Psychopharmacology 15:18-21. Hocaoğlu Ç, Okumuş B (2018) Psychiatric manifestations and brain tumor: A case report and brief review. The Medical Journal of Mustafa Kemal University 9:42-9. Oreskovic NM, Strother CG, Zibners LM (2007) An unusual case of a central nervous system tumor presenting as a chief complaint of depression. Pediatric Emergency Care 23:486-8. Rooney A, Carson A, Grant R (2011) Depression in cerebral glioma patients: a systematic review of observational studies. J Natl Cancer Inst103:61-76. Rouchell AM, Pounds R, Tierney JG (2002) Depression Textbook of Consultation-Liaison Psychiatry, 2nd Edition, Volume 1. MG Wise, JR Rundell (Ed), Washington DC American Psychiatric Publishing, Inc, p.307-38. Özen SÖ, Hayriye ME (2004) Bedensel Hastalıklarda Depresyon. Klinik Psikiyatri Ek 2:63-9. Sözeri Varma G , Bingöl C , Topak O et al (2019) Relationship of apathy with depressive symptom severity and cognitive functions in geriatric depression. Arch Neuropsychiatry 56:133-8. Yuen GS, Gunning FM, Woods E et al (2014) Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response. J Affect Disord 166:179-86.

Patients with dementia and their caregivers 3 years after diagnosis. A longitudinal study.

To document caregivers' perceptions of the deterioration in functional ability of persons with dementia over time, to identify the most problematic behavior for caregivers at two stages of dementing illness, and to compare the perceived informational needs of caregivers at diagnosis and 3 years later. Single cohort. Surveys were mailed at time 1 and respondents were followed up after 3 years (time 2). Midwestern hospital dementia assessment clinic with a family physician director. Continuing care was by community physicians. Thirty elderly patients with dementia who were evaluated at the dementia clinic. Data were provided by their caregivers. Patients' scores on the Activities of Daily Living section of the questionnaire declined (bathe self, P = .03; transfer from bed or chair, P = .03; and groom self, P = .06). Significant deterioration in behaviors over time was found in incontinence (P = .04). Fewer patients were depressed at time 2 (P = .02). The patient behaviors found most troublesome at time 1 were worrying about memory loss, losing or hiding things, feeling blue, experiencing restlessness, having difficulty calculating, experiencing a lack of interest, and having false ideas. At time 2, the greatest problems were having a short attention span, failing to recognize persons or things, experiencing a lack of interest, experiencing restlessness, repeating himself or herself, forgetting where he or she is, speaking incoherently, and being incontinent. Questions caregivers most wanted answered at time 1 concerned possible treatment, the future course of illness, and the cause of the symptoms. At time 2, the concerns were the future course of illness, possible treatment, and disease inheritance. There was significantly more interest in family agreement about care (P = .004) and the need for legal guardianship (P = .001) at time 2. Caregivers' perceptions of the most frequent and troublesome behaviors of patients with dementia were documented at different stages of the disease. The importance caregivers attached to their requests for information reflected changing but continuing needs for reassurance about the patient's diagnosis and treatment and for help with the psychosocial consequences of dementia. Physicians must be aware of caregivers' needs at different stages of the disease process and be equipped to help them appropriately.

Music therapy for Alzheimer's disease

The forms of music therapy are broad in nature, and can range from individual or group singing sessions, to active participation in music making, to listening to songs individually. Alzheimer’s disease (AD) is a fatal disease that continuously deteriorates brain chemistry over time. Accounting for more than 60% of the dementia in older people, AD gradually leads to detrimental effects on cognitive function, linguistic abilities, and memory. Within populations living with Alzheimer's, music therapy is sometimes used to assist in palliating the behavioral and psychological symptoms of this disease. Music therapy is based in scientific findings and can elicit change in individuals as well as groups through music. Personalized music therapy has been shown in some cases to be able to lessen certain symptoms, including behavioral symptoms, such as physical or verbal outbursts and hallucinations, and cognitive symptoms related to dementia.

Update on diagnostic methods, natural history and outcome variables in Alzheimer's disease.

The diagnosis of Alzheimer's disease (AD) currently relies on history obtained from family or friends and on mental status assessment matched to National Institute of Neurological and Communicative Disorders and Stroke criteria. Progression over time may or may not be typical, suggesting alternate diagnoses such as Lewy body or frontotemporal dementias. Apolipoprotein E genotype does not appear to be useful as a diagnostic marker. The usefulness of brain imaging in AD must be reexamined. Critical events in the natural history of AD, such as institutionalization and loss of ability for self-care, could be used as end points. Loss of ability for instrumental tasks, such as driving, traveling alone, or managing finances, would be preferable for early-stage stabilization studies. Different symptomatic domains of AD (mood, cognition, functional autonomy, behavior, motoricity) can be quantified using specific outcome measures. Although cognitive loss has been considered a core symptom of AD from a regulatory perspective, loss of functional autonomy and behavioral disinhibition are considered more important by clinicians and families. Recently, the availability of new scales has led to an interest in all of these domains. Results from symptomatic drug studies suggest a differential effect of cholinesterase inhibitors on cognition versus muscarinic agonists on functional autonomy and behavior. Hence there is a need to measure these domains separately and, eventually, to attempt combination therapy. Quality of life is a difficult but important dimension of AD therapeutic research, and it requires further methodological research.

Most families tend to realize progress of Alzheimer's disease when behavioural and psychological symptoms are obvious.

Alzheimer's disease (AD) is a common cognitive disease that can progress at an accelerating rate. Even with early diagnosis, the families might not recognize AD progressing unless behavioural and psychological symptoms of dementia (BPSD) develop. In many cases, discrepancies could exist between family-assessed AD stage and diagnosed AD stage. This study explored such discrepancies and potential clinical implications. Participants were 161 new outpatients with AD or mild cognitive impairment at four memory clinics whose AD stage was diagnosed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We classified patients into four groups according to AD severity. Family members completed the Functional Assessment Staging (FAST) scale during an interview. We then assigned patients to three groups according to discrepancies between family-assessed and diagnosed AD stage. Families also completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), which assesses 12 neuropsychiatric domains, in order to examine the presence of BPSD in relation to AD stage. Most families (74%-80%) assessed patients as having milder AD than the diagnosed stage. NPI-Q scores and duration of education significantly affected discrepancies with HDS-R and MMSE scores. The NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance significantly affected family-assessed FAST. Families of patients with more years of education assessed the AD stage as more advanced than the diagnosed stage. Surprisingly, living together did not significantly affect the discrepancy. Most families assessed AD as milder than the clinically diagnosed AD stage. In addition, high NPI-Q scores and more years of school education significantly affected the discrepancy. Family-assessed FAST was significantly affected by the NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance. These results suggest that obvious BPSD are significant factors for Japanese families to recognize AD progress.

Signs and symptoms of Parkinson's disease

Neuropsychiatric Parkinson's disease causes neuropsychiatric disturbances, which mainly include cognitive disorders, mood disorders, and behavior problems, and can be as disabling as motor symptoms. Since L-Dopa, the widely used drug in Parkinson's disease treatment, is decarboxylated by aromatic L-amino acid decarboxylase (AADC), which is found in both dopaminergic and serotonergic neurons, it is possible for serotonergic neurons to convert L-Dopa into dopamine and generate excessive neuronal death by creating reactive oxygen species and quinoproteins. The association of serotonin with mood and cognition may explain some of the side-effects observed in patients treated with L-Dopa due to serotonin deficit.

Psychiatric symptomatology and prodromal Alzheimer's disease.

The aim of this study was to determine the prevalence of psychiatric symptoms among nondemented individuals with memory changes and whether such symptoms predict progression of functional decline or diagnosis of Alzheimer disease (AD). A semi-structured interview was administered at baseline to controls (n = 32) and to nondemented subjects with memory changes (n = 112) and to each subject's collateral source. The interview assessed the impact of cognition on functional abilities in daily life and a variety of psychiatric symptoms, including symptoms of psychosis, depression, and personality change. Participants were followed annually for 3 years to determine who had progressive functional decline and who progressed to meet clinical criteria for AD. Those diagnosed with AD on follow-up had more symptoms of personality change, such as agitation and passivity, at baseline than those who did not progress to meet clinical criteria for AD. Mild depressive symptoms were also more common among individuals at baseline who subsequently 'converted' to AD. Symptoms of personality change were associated with a more rapid increase in functional difficulty over time, whereas depressive symptoms were not. Changes in personality are more common among subjects with memory changes who go on to develop AD. Particular types of personality change, such as agitation and passivity, are related to progression of functional difficulty over time. Depressive symptoms, although common in prodromal AD, are not associated with a more rapid functional decline.

Post-concussion syndrome

Psychological and behavioral Psychological conditions, which are present in about half of people with PCS, may include irritability, anxiety, depression, and a change in personality. Other emotional and behavioral symptoms include restlessness, aggression, and mood swings. Some common symptoms, such as apathy, insomnia, irritability, or lack of motivation, may result from other co-occurring conditions, such as depression. Higher mental functions Common symptoms associated with a diagnosis of PCS are related to cognition, attention, and memory, especially short-term memory, which can also worsen other problems such as forgetting appointments or difficulties at work. In one study, one in four people diagnosed with PCS continued to report memory problems a year after the injury, but most experts agree that cognitive symptoms clear within six months to a year after injury in the vast majority of individuals.

Progression of cognitive impairment in Alzheimer's disease.

Change in cognitive function was assessed over 12 months in 110 patients over the age of 65 satisfying National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for "probable" Alzheimer's Disease. A highly significant deterioration in cognitive function was observed. Decline in cognitive scores was relatively normally distributed. Patients who died during the follow-up had more apraxia at entry to the study than survivors. A greater rate of decline was seen in patients whose parents suffered from dementia (but not in those where a sibling or other relative was affected), in subjects who had moderate dementia, and those who had been ill for less than 24 months. Age, age of onset, and the presence or absence of aphasia or apraxia had no influence on rate of progression. A cluster analysis revealed three patterns of decline.

Anti-NMDA receptor encephalitis

Prior to the development of a symptom complex that is specific to anti-NMDA receptor encephalitis, people may experience prodromal symptoms, including headaches, flu-like illness, or symptoms similar to an upper respiratory infection. These symptoms may be present for weeks or months prior to disease onset. Beyond the prodromal symptoms, the disease progresses at varying rates, and patients may present with a variety of neurologic symptoms. During the initial stage of the disease, symptoms vary slightly between children and adults. However, behavior changes are a common first symptom within both groups. These changes often include agitation, paranoia, psychosis, and violent behaviors. Other common first manifestations include seizures and bizarre movements, mostly of the lips and mouth, but also including pedaling motions with the legs or hand movements resembling playing a piano. Some other symptoms typical during the disease onset include impaired cognition, memory deficits, and

Long-term cognitive and functional decline in late onset Alzheimer's disease: therapeutic implications.

National Institute of Clinical Excellence guidelines advocate the use of the Mini-Mental Test Examination and a functional assessment as a means of measuring treatment response. However, there is little knowledge of the change expected in those with Alzheimer's disease in clinical practice. to describe the long-term variability of the Mini-Mental Test Examination and Blessed Dementia Rating Scale. 374 Alzheimer's disease patients referred to psychiatric services in southeast London were followed annually over a 3-year period. the mean Mini-Mental Test Examination score for the total group at baseline was 9.9 points. Individual variability in the rate of cognitive and functional decline is large and around 40% of patients after 1 year, and up to one-quarter of patients after 3 years who survived, show no change or an improvement in scores compared with baseline measures. in the evaluation of individual treatment response the rate of change, as measured by the Mini-Mental Test Examination and Blessed Dementia Rating Scale, is of limited value.

Outline of the human brain

Neurodegeneration and dementia Neurodegeneration – an umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Multiple sclerosis – an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged. Parkinson's disease – Early symptoms include shaking, rigidity, slowness of movement and difficulty with walking and gait. Later symptoms include cognitive and behavioral problems, with dementia commonly occurring in the advanced stages. The motor symptoms result from the death of dopamine-generating cells in a region of the mid-brain. Alzheimer's disease – The most common form of dementia. Beginning with an array of symptoms including memory loss, as the disease progresses the individual often withdraws from family and society and requires 24/7 supervision. It is predicted to affect 1 in 85 people globally by 2050.

A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration.

This study measured the annual rate of cognitive change in patients with Alzheimer's disease and determined the effects of clinical variables on that rate. It also compared the ability of two cognitive scales to measure change over the entire range of dementia severity. The cognitive subscale of the Alzheimer's Disease Assessment Scale and the Blessed test for information memory and concentration were given to 111 patients with Alzheimer's disease and 72 nondemented elderly comparison subjects at 6-month intervals for up to 90 months. Longitudinal changes in scores on the cognitive subscale were measured with several different methods of data analysis. For the patients with Alzheimer's disease, the annual rate of change in cognitive subscale scores showed a quadratic relationship with dementia severity in which deterioration was slower for mildly and severely demented patients than for patients with moderate dementia. Gender, age at onset, and family history of dementia had no effect on the rate of cognitive deterioration. The comparison group showed a slight improvement in cognitive performance over time. All data analytic methods gave similar results. The cognitive subscale of the Alzheimer's Disease Assessment Scale was more sensitive to change in both mild and severe dementia than was the Blessed test. These results suggest that cognitive deterioration is slow during the early and very late stages of Alzheimer's disease and more rapid during the middle stages. No clinical variables other than degree of cognitive impairment and previous rate of cognitive decline predicted rate of deterioration. These results have implications for treatment trials and attempts to identify subgroups.

Parkinson's disease

Attempts to classify PD into different subtypes have been made, with focus put on age at onset, progression of symptoms and dominance of tremor, but none have been adopted. Signs and symptoms The most recognizable early symptoms are movement ("motor") related. Non-motor symptoms, including autonomic dysfunction (dysautonomia), neuropsychiatric problems (mood, cognition, behavior or thought alterations), and sensory (especially altered sense of smell) and sleep difficulties, are usually associated with later stages, but may present at the time of diagnosis. Motor Four motor symptoms are considered as cardinal signs in PD: tremor, slowness of movement (bradykinesia), rigidity, and postural instability.

Predictors of cognitive and functional progression in patients with probable Alzheimer's disease.

We followed 65 patients with probable Alzheimer's disease, who were initially mildly to moderately impaired, with semiannual assessments of cognitive and functional performance for up to 4 years. Scores on the Mini Mental State Examination and a combination of instrumental and self-maintenance scale of activities of daily living were regressed on time of examination (measured in 6-month increments) to estimate cognitive and functional progression rates in individual patients. Lower scores on the verbal neuropsychological tests at the time of study entry, more aggressive behavior, and sleep disturbance during the first year of observation predicted faster cognitive progression. Faster functional progression was predicted by paranoid behavior, hallucinations and activity disturbances during the first year and the presence of extrapyramidal signs and lower scores on nonverbal neuropsychological tests at the time of entry into the study. Hallucinations occurred independently of cognitive severity and may identify a distinct subgroup of patients with rapid functional progression. Because of the greater significance of functional progression for caregivers' ability to manage patients, the presence of specific behavior problems early in the disease course may help to identify individuals who will experience greater functional decline and be at risk for earlier institutionalization.

Sex differences in memory

Multiple studies have found that there is a significant difference in the symptoms of Alzheimer's disease that affect the sexes. Some of these behavioral and psychological symptoms of dementia (BPSD) include depression, anxiety, dysphoria, nighttime disturbances, and aggression. Several recent studies have found that women tend to exhibit symptoms such as depression and anxiety more often than men. One study has even gone as far as to suggest that having depression at any point during midlife increases chances of Alzheimer's Disease developing later by up to 70%. Men, on the other hand, exhibit symptoms such as aggression and other socially inappropriate behaviors more often. In addition, it has been found that men are more likely to have coronary artery disease which has been known to damage the blood brain barrier (BBB) by causing micro vascular lesions. Damage to the blood brain barrier seems to be connected to cognitive decline and several forms of dementia, including Alzheimer's