This issue of International Psychogeriatrics contains two systematic reviews (Collins et al., Reference Collins, Henley and Suarez-Gonzalez2023; Crawley et al., Reference Crawley, Sampson, Moore, Kupeli and West2023) and a case-control study (Kanemoto et al., Reference Kanemoto2023) focused on specific aspects – that is neuropsychiatric symptoms (NPS), post-bereavement grief in caregivers, and predictor of response to an intervention, in different types of dementias including Alzheimer’s disease (AD), frontotemporal dementia (FTD), primary progressive aphasia, posterior cortical atrophy, young-onset AD (YOAD), and inherited dementias. There is another empirical study comparing survival and mortality in patients with late-onset versus young-onset vascular dementia (Yoo et al., Reference Yoo2023) and a commentary on it (Rodda and Carter, Reference Rodda and Carter2023).
(1) Neuropsychiatric symptoms (NPS) in less common forms of dementia
Dementias are the most common major neuropsychiatric disorders in older adults (Reynolds et al., Reference Reynolds, Jeste, Sachdev and Blazer2022). Much of the research in this area has targeted AD, including its early detection and the occurrence of NPS. Yet, significant predictors of a delayed diagnosis of dementia include younger age at onset, dementia type other than AD, and increased number of services consulted (Giebel, Reference Giebel2022; Loi et al., Reference Loi2022). NPS in dementia are a group of non-cognitive symptoms that occur in over 90% of individuals with dementia (Tampi and Jeste, Reference Tampi and Jeste2022). Apathy is perhaps the most common NPS, occurring in about 70% of persons with AD and related disorders (ADRD). Depression is seen in about 40% of the patients, while approximately 50% of the persons with ADRD have delusions and/or hallucinations. Psychosis of AD may be a distinct subtype of that dementia. Specific diagnostic criteria have been proposed for psychosis of ADRD (Sano et al., Reference Sano, Cummings, Jeste, Finkel and Reichman2022). NPS are also common in persons with Lewy body dementia. However, much less literature is available on NPS in less common forms of dementias such as FTD including its behavioral variant (bv-FTD), primary progressive aphasia, especially its semantic variant (sv-PPA), posterior cortical atrophy, YOAD, and inherited dementias.
Collins et al. (Reference Collins, Henley and Suarez-Gonzalezthis issue), present an excellent systematic review of the prevalence of depression, anxiety, and apathy in FTD, atypical and young-onset AD, and inherited dementia. Apathy was reported to have high prevalence across all phenotypes, especially in bv-FTD (73–100%), overall FTD (50–100% across studies), and YOAD (44–100%). The high prevalence of apathy in bv-FTD is not surprising, since apathy is one of the diagnostic criteria for bv-FTD. Although less common than apathy, symptoms of anxiety and depression were also reported across all phenotypes. Anxiety was observed in FTD (0–100%) and bv-FTD (19–63%). Depression had the highest prevalence in FTD (7–69%) and YOAD (11–55%). These findings suggest that depression and anxiety may be overlapping processes in these dementias, possibly sharing related underlying mechanisms.
As Collins et al. (Reference Collins, Henley and Suarez-Gonzalezthis issue) point out, the individual studies in their review had several limitations. Inconsistency in the tools used to measure symptoms and small sample sizes were common methodological shortcomings. There was also considerable variability in methods such as the severity cutoff at which NPS was considered to be present, location from which participants were recruited, and the sampling procedure used (e.g. random vs. convenience sampling). There was also a risk of information bias depending on which NPS were being studied by each group of investigators. For instance, depression was more frequently measured than anxiety and apathy. A number of the studies were cross-sectional, making any causative interpretations problematic. The average quality of studies was moderate, and very few investigations examined NPS over the course of neurocognitive decline.
The authors make several useful recommendations for future research. Large sample sizes of rare dementias are difficult to gather in a single center; therefore, multicentric collaborations are needed to strengthen the quality of evidence. Expert consensus should be obtained to harmonize research protocols on how to carry out investigations on NPS in general and in rare dementias in particular. This should include agreement about outcome measures to use, optimum sample size, level of description of the sample, and a need for stratification by disease severity. The accuracy of information provided by proxy measures can be improved by combining caregiver and patient-derived measures using purpose-built tools and validated symptom-specific instruments. Quality of life should be added as a secondary outcome measure in these studies. I want to add that research is also needed on the management of NPS in all forms of dementia. Research on NPS in ADRD shows that several nonpharmacological interventions are beneficial and are recommended as first-line treatments (Tampi and Jeste, Reference Tampi and Jeste2022). Pharmacotherapy should be reserved for the treatment of more severe or refractory NPS or where nonpharmacological management is not feasible. Atypical antipsychotics have shown mostly modest benefits in reducing NPS in persons with ADRD, and their use is limited by their adverse effect profiles. Pharmacological and psychosocial interventions should be tested for preventing and treating NPS in less common forms of dementia.
(2) Prolonged grief following bereavement in dementia caregivers
Bereavement and grief are a normal part of life, especially in older adults. Losing a loved one is one of life’s greatest stressors. Although most bereaved individuals navigate through a period of intense acute grief that lessens with time, approximately 10% will develop a prolonged grief condition that interferes with everyday life and involves severe long-term reactions to the loss that impact everyday functioning. In a beautiful book of poems, Natasha Josefowitz (Reference Josefowitz2013) describes the painful first year after her husband’s death. She found herself lonely and felt mentally isolated and unable to live a life without the one she could not live without. Slowly, she realized though that she had to re-invent herself while a vital part of her life was gone forever. She successfully managed to do that, despite knowing that it would be a long and agonizing journey to make herself whole.
There has been growing literature on grief research in family caregivers of people with dementia. Researchers and clinicians have been attempting to differentiate normal bereavement from pathological grief. The terms prolonged grief disorder (PGD) and complicated grief (CG) are being commonly used in recent years. PGD is characterized by symptoms such as longing for and preoccupation with the deceased, emotional distress, and significant functional impairment for at least 6 months after the loss. CG, largely similar to PGD, is characterized by intense grief that lasts longer than would be expected according to social norms and impairment in daily functioning. Crawley et al. (Reference Crawley, Sampson, Moore, Kupeli and Westthis issue) present a systematic review of grief in family caregivers of people with dementia. These reviewers focused on the prevalence of pre-death and post-death grief, and associated factors, the relationship between pre-death factors and post-death grief, and the services used to manage grief in unpaid family caregivers of persons with AD or any other type of dementia. Quantitative data from 55 studies, most of which included only the spouse or adult child caregivers, were analyzed. Eighty percent of these studies were rated as high-quality reports. Being a spouse, lower level of education, caring for a person with advanced dementia, greater burden, and more severe depression were associated with more intense pre-death grief. Lower education level and greater depression were also predictive of higher post-death grief. The authors recommend that awareness of these characteristics, which increase the likelihood of higher grief, can help clinicians identify quickly the individuals who are in clear need of support.
The review has several strengths. It is very well-written, scholarly, comprehensive, and balanced. Its limitations stem mainly from the shortcomings of the individual studies included. For example, despite an abundance of research in this area, it is not possible to determine the precise prevalence of high pre-death grief among family caregivers of individuals with dementia, based on validated grief assessment measures. While the included studies were conducted in a number of different countries, lower and lower-middle-income countries were underrepresented in this research body. There is an obvious need for studies of caregivers of individuals with dementia in different parts of the world as there are important differences in grief experiences across cultures.
The recent publication of the DSM-5-Text Revision, which has included diagnostic criteria for the newly added entity of PGD, could not be more timely or important (American Psychiatric Association, 2022). The COVID-19 pandemic has led to immense societal and individual level disconnection in multiple ways – socioeconomic, political, medical, psychological, and spiritual. PGD is not a category encompassing all disorders of grief and mourning but refers to a particular form of grief that is debilitating and pernicious (Reynolds et al., Reference Reynolds2023). Clinicians need to understand and navigate the vicissitudes of normal grief and to recognize when adaptation to and acceptance of bereavement have been derailed. Under those circumstances, grief becomes prolonged, with an intensity, a longing for, and a preoccupation with the spousal death that makes the caregiver feel that the loss occurred just recently rather than years or even decades ago.
Assessment of caregivers following bereavement may include the PGD-13 R checklist and the Structured Clinical Interview for PGD (Reynolds et al., Reference Reynolds2023). Early detection of depression in dementia caregivers is highly recommended. Self-reported activity restriction is an established correlate of depression in dementia caregivers. Smagula et al. (Reference Smagula2023) have reported that objectively measured morning activity levels predicted the degree of depression six months later in caregivers of persons with dementia. Strategies for the clinical management of grief and specific treatment for PGD, together with tips on when to refer for specialty care, must be considered. As Crawley et al. (Reference Crawley, Sampson, Moore, Kupeli and West2023) point out, particular demographic features and psychosocial characteristics play a role in development of CG in these family caregivers. Future research should consider the interplay of risk and protective factors and focus on potentially modifiable elements such as social support. There is limited evidence regarding service use in this population, and investigators should also focus on what components of support or service provision are needed for caregivers with regard to CG.
(3) A biomarker predictor of improvement in normal pressure hydrocephalus
Kanemoto et al. (Reference Kanemotothis issue) report a case-control study of cerebrospinal fluid (CSF) amyloid beta biomarkers and response of cognition to a tap test in idiopathic normal pressure hydrocephalus (iNPH). NPH is a potentially treatable disorder resulting from an accumulation of CSF. Its diagnosis is based on the evaluation of clinical symptoms, which consist of a classic Hakim triad: gait disturbances, cognitive impairment, and urinary incontinence (Micchia et al., Reference Micchia2022). In older adults, iNPH has a prevalence rate of 2.1 to 2.8%, and its symptoms are typically relieved following CSF shunt surgery. However, which symptoms improve and the extent of their improvement are variable. A number of tests have been used to predict possible response to surgery, including brain MRI, formalized neuropsychological and gait testing, large-volume lumbar puncture, and prolonged lumbar drainage, but no single test has been validated to rule out potential response to surgery (Shprecher et al., Reference Shprecher, Schwalb and Kurlan2008). Clinically, shunt surgery is considered when at least one of the three above-mentioned symptoms is found to have improved after transient removal of excess CSF (tap test). However, the sensitivity of the tap test is not high enough. The tap test has a high positive value as a predictor of therapeutic response, but a negative test does not rule out a possibility of improvement with the treatment (Passos-Neto et al., Reference Passos-Neto, Lopes, Teixeira, Studart Neto and Spera2022).
Comorbid AD pathology is likely to affect the response to the tap test. Yet, there are few investigations exploring the association between tap test responsiveness and presence of AD pathology in patients with iNPH. Kanemoto et al. Reference Kanemoto(this issue) recruited 108 patients with possible iNPH, divided them into two groups according to their tap test response, and compared CSF AD biomarkers to determine the effects of AD comorbidity on tap test response. While many studies have focused on inflammatory and neuronal injury biomarkers of AD (Wang et al., Reference Wang2022), decreased Aβ42/40 ratio and increased total tau in CSF have been reported to be more useful biomarkers for a diagnosis of AD. The Aβ42/40 ratio has been suggested as a superior measure for the identification of AD pathology compared to concentrations of Aβ1-42 alone. Kanemoto et al. (Reference Kanemoto2023) found that the Aβ42/40 ratio was significantly lower and the total tau concentration was significantly higher in the CSF of iNPH patients who did not show an improvement on the tap test compared to those who did, even after adjusting for the degree and duration of iNPH symptoms. Among the triad symptoms of iNPH, the response in the cognitive domain, but not in the gait or urination domains, was associated with Aβ42/40 ratio. This is the first study to suggest that iNPH patients with concomitant AD pathology were less responsive to the tap test, similar to the association between shunt unresponsiveness and presence of AD pathology in iNPH, even after controlling for disease duration and symptom severity.
This study has several strengths. The total number of iNPH participants was relatively large. A few previous studies have reported an association between AD pathology and tap test responsiveness in iNPH, but the sample sizes were too small to allow for multiple comparison adjustment or multivariate analysis. The authors also point out some limitations to their study. As the concentrations of proteins in the CSF, including Aβ and total tau, have been reported to be different between iNPH patients and healthy subjects, the concentration of Aβ and total tau in the CSF of iNPH patients may not be the best biomarker for AD pathology. No cutoff values of CSF biomarkers to detect AD pathology in the authors’ laboratory were used and so, the exact results may not generalize to other labs. The effect of CSF removal is generally larger in a shunt surgery than in a tap test. Even in the iNPH group that did not improve with the tap test, improvement was seen after shunt surgery in a small proportion of the patients. It will be useful to follow the results of shunting in the patients with a negative tap test.
Appropriately, Kanemoto et al. conclude that the tap test should be used in considering shunt surgery in persons with iNPH, along with CSF biomarkers. The effect of AD comorbidity on tap test response in overall cognition was significant albeit small. Detailed neuropsychological evaluation for memory and frontal lobe function revealed a significant improvement even in those in whom the MMSE did not improve. Thus, a detailed cognitive test battery may be a useful tool to evaluate the cognitive response to a tap test, although the degree of cognitive improvement may be small in iNPH patients with low CSF Aβ42/40 ratio.
Thus, these three articles clearly help advance our understanding and management of patients with different types of dementias and suggest useful pathways to future research.
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This issue of International Psychogeriatrics contains two systematic reviews (Collins et al., Reference Collins, Henley and Suarez-Gonzalez2023; Crawley et al., Reference Crawley, Sampson, Moore, Kupeli and West2023) and a case-control study (Kanemoto et al., Reference Kanemoto2023) focused on specific aspects – that is neuropsychiatric symptoms (NPS), post-bereavement grief in caregivers, and predictor of response to an intervention, in different types of dementias including Alzheimer’s disease (AD), frontotemporal dementia (FTD), primary progressive aphasia, posterior cortical atrophy, young-onset AD (YOAD), and inherited dementias. There is another empirical study comparing survival and mortality in patients with late-onset versus young-onset vascular dementia (Yoo et al., Reference Yoo2023) and a commentary on it (Rodda and Carter, Reference Rodda and Carter2023).
(1) Neuropsychiatric symptoms (NPS) in less common forms of dementia
Dementias are the most common major neuropsychiatric disorders in older adults (Reynolds et al., Reference Reynolds, Jeste, Sachdev and Blazer2022). Much of the research in this area has targeted AD, including its early detection and the occurrence of NPS. Yet, significant predictors of a delayed diagnosis of dementia include younger age at onset, dementia type other than AD, and increased number of services consulted (Giebel, Reference Giebel2022; Loi et al., Reference Loi2022). NPS in dementia are a group of non-cognitive symptoms that occur in over 90% of individuals with dementia (Tampi and Jeste, Reference Tampi and Jeste2022). Apathy is perhaps the most common NPS, occurring in about 70% of persons with AD and related disorders (ADRD). Depression is seen in about 40% of the patients, while approximately 50% of the persons with ADRD have delusions and/or hallucinations. Psychosis of AD may be a distinct subtype of that dementia. Specific diagnostic criteria have been proposed for psychosis of ADRD (Sano et al., Reference Sano, Cummings, Jeste, Finkel and Reichman2022). NPS are also common in persons with Lewy body dementia. However, much less literature is available on NPS in less common forms of dementias such as FTD including its behavioral variant (bv-FTD), primary progressive aphasia, especially its semantic variant (sv-PPA), posterior cortical atrophy, YOAD, and inherited dementias.
Collins et al. (Reference Collins, Henley and Suarez-Gonzalezthis issue), present an excellent systematic review of the prevalence of depression, anxiety, and apathy in FTD, atypical and young-onset AD, and inherited dementia. Apathy was reported to have high prevalence across all phenotypes, especially in bv-FTD (73–100%), overall FTD (50–100% across studies), and YOAD (44–100%). The high prevalence of apathy in bv-FTD is not surprising, since apathy is one of the diagnostic criteria for bv-FTD. Although less common than apathy, symptoms of anxiety and depression were also reported across all phenotypes. Anxiety was observed in FTD (0–100%) and bv-FTD (19–63%). Depression had the highest prevalence in FTD (7–69%) and YOAD (11–55%). These findings suggest that depression and anxiety may be overlapping processes in these dementias, possibly sharing related underlying mechanisms.
As Collins et al. (Reference Collins, Henley and Suarez-Gonzalezthis issue) point out, the individual studies in their review had several limitations. Inconsistency in the tools used to measure symptoms and small sample sizes were common methodological shortcomings. There was also considerable variability in methods such as the severity cutoff at which NPS was considered to be present, location from which participants were recruited, and the sampling procedure used (e.g. random vs. convenience sampling). There was also a risk of information bias depending on which NPS were being studied by each group of investigators. For instance, depression was more frequently measured than anxiety and apathy. A number of the studies were cross-sectional, making any causative interpretations problematic. The average quality of studies was moderate, and very few investigations examined NPS over the course of neurocognitive decline.
The authors make several useful recommendations for future research. Large sample sizes of rare dementias are difficult to gather in a single center; therefore, multicentric collaborations are needed to strengthen the quality of evidence. Expert consensus should be obtained to harmonize research protocols on how to carry out investigations on NPS in general and in rare dementias in particular. This should include agreement about outcome measures to use, optimum sample size, level of description of the sample, and a need for stratification by disease severity. The accuracy of information provided by proxy measures can be improved by combining caregiver and patient-derived measures using purpose-built tools and validated symptom-specific instruments. Quality of life should be added as a secondary outcome measure in these studies. I want to add that research is also needed on the management of NPS in all forms of dementia. Research on NPS in ADRD shows that several nonpharmacological interventions are beneficial and are recommended as first-line treatments (Tampi and Jeste, Reference Tampi and Jeste2022). Pharmacotherapy should be reserved for the treatment of more severe or refractory NPS or where nonpharmacological management is not feasible. Atypical antipsychotics have shown mostly modest benefits in reducing NPS in persons with ADRD, and their use is limited by their adverse effect profiles. Pharmacological and psychosocial interventions should be tested for preventing and treating NPS in less common forms of dementia.
(2) Prolonged grief following bereavement in dementia caregivers
Bereavement and grief are a normal part of life, especially in older adults. Losing a loved one is one of life’s greatest stressors. Although most bereaved individuals navigate through a period of intense acute grief that lessens with time, approximately 10% will develop a prolonged grief condition that interferes with everyday life and involves severe long-term reactions to the loss that impact everyday functioning. In a beautiful book of poems, Natasha Josefowitz (Reference Josefowitz2013) describes the painful first year after her husband’s death. She found herself lonely and felt mentally isolated and unable to live a life without the one she could not live without. Slowly, she realized though that she had to re-invent herself while a vital part of her life was gone forever. She successfully managed to do that, despite knowing that it would be a long and agonizing journey to make herself whole.
There has been growing literature on grief research in family caregivers of people with dementia. Researchers and clinicians have been attempting to differentiate normal bereavement from pathological grief. The terms prolonged grief disorder (PGD) and complicated grief (CG) are being commonly used in recent years. PGD is characterized by symptoms such as longing for and preoccupation with the deceased, emotional distress, and significant functional impairment for at least 6 months after the loss. CG, largely similar to PGD, is characterized by intense grief that lasts longer than would be expected according to social norms and impairment in daily functioning. Crawley et al. (Reference Crawley, Sampson, Moore, Kupeli and Westthis issue) present a systematic review of grief in family caregivers of people with dementia. These reviewers focused on the prevalence of pre-death and post-death grief, and associated factors, the relationship between pre-death factors and post-death grief, and the services used to manage grief in unpaid family caregivers of persons with AD or any other type of dementia. Quantitative data from 55 studies, most of which included only the spouse or adult child caregivers, were analyzed. Eighty percent of these studies were rated as high-quality reports. Being a spouse, lower level of education, caring for a person with advanced dementia, greater burden, and more severe depression were associated with more intense pre-death grief. Lower education level and greater depression were also predictive of higher post-death grief. The authors recommend that awareness of these characteristics, which increase the likelihood of higher grief, can help clinicians identify quickly the individuals who are in clear need of support.
The review has several strengths. It is very well-written, scholarly, comprehensive, and balanced. Its limitations stem mainly from the shortcomings of the individual studies included. For example, despite an abundance of research in this area, it is not possible to determine the precise prevalence of high pre-death grief among family caregivers of individuals with dementia, based on validated grief assessment measures. While the included studies were conducted in a number of different countries, lower and lower-middle-income countries were underrepresented in this research body. There is an obvious need for studies of caregivers of individuals with dementia in different parts of the world as there are important differences in grief experiences across cultures.
The recent publication of the DSM-5-Text Revision, which has included diagnostic criteria for the newly added entity of PGD, could not be more timely or important (American Psychiatric Association, 2022). The COVID-19 pandemic has led to immense societal and individual level disconnection in multiple ways – socioeconomic, political, medical, psychological, and spiritual. PGD is not a category encompassing all disorders of grief and mourning but refers to a particular form of grief that is debilitating and pernicious (Reynolds et al., Reference Reynolds2023). Clinicians need to understand and navigate the vicissitudes of normal grief and to recognize when adaptation to and acceptance of bereavement have been derailed. Under those circumstances, grief becomes prolonged, with an intensity, a longing for, and a preoccupation with the spousal death that makes the caregiver feel that the loss occurred just recently rather than years or even decades ago.
Assessment of caregivers following bereavement may include the PGD-13 R checklist and the Structured Clinical Interview for PGD (Reynolds et al., Reference Reynolds2023). Early detection of depression in dementia caregivers is highly recommended. Self-reported activity restriction is an established correlate of depression in dementia caregivers. Smagula et al. (Reference Smagula2023) have reported that objectively measured morning activity levels predicted the degree of depression six months later in caregivers of persons with dementia. Strategies for the clinical management of grief and specific treatment for PGD, together with tips on when to refer for specialty care, must be considered. As Crawley et al. (Reference Crawley, Sampson, Moore, Kupeli and West2023) point out, particular demographic features and psychosocial characteristics play a role in development of CG in these family caregivers. Future research should consider the interplay of risk and protective factors and focus on potentially modifiable elements such as social support. There is limited evidence regarding service use in this population, and investigators should also focus on what components of support or service provision are needed for caregivers with regard to CG.
(3) A biomarker predictor of improvement in normal pressure hydrocephalus
Kanemoto et al. (Reference Kanemotothis issue) report a case-control study of cerebrospinal fluid (CSF) amyloid beta biomarkers and response of cognition to a tap test in idiopathic normal pressure hydrocephalus (iNPH). NPH is a potentially treatable disorder resulting from an accumulation of CSF. Its diagnosis is based on the evaluation of clinical symptoms, which consist of a classic Hakim triad: gait disturbances, cognitive impairment, and urinary incontinence (Micchia et al., Reference Micchia2022). In older adults, iNPH has a prevalence rate of 2.1 to 2.8%, and its symptoms are typically relieved following CSF shunt surgery. However, which symptoms improve and the extent of their improvement are variable. A number of tests have been used to predict possible response to surgery, including brain MRI, formalized neuropsychological and gait testing, large-volume lumbar puncture, and prolonged lumbar drainage, but no single test has been validated to rule out potential response to surgery (Shprecher et al., Reference Shprecher, Schwalb and Kurlan2008). Clinically, shunt surgery is considered when at least one of the three above-mentioned symptoms is found to have improved after transient removal of excess CSF (tap test). However, the sensitivity of the tap test is not high enough. The tap test has a high positive value as a predictor of therapeutic response, but a negative test does not rule out a possibility of improvement with the treatment (Passos-Neto et al., Reference Passos-Neto, Lopes, Teixeira, Studart Neto and Spera2022).
Comorbid AD pathology is likely to affect the response to the tap test. Yet, there are few investigations exploring the association between tap test responsiveness and presence of AD pathology in patients with iNPH. Kanemoto et al. Reference Kanemoto(this issue) recruited 108 patients with possible iNPH, divided them into two groups according to their tap test response, and compared CSF AD biomarkers to determine the effects of AD comorbidity on tap test response. While many studies have focused on inflammatory and neuronal injury biomarkers of AD (Wang et al., Reference Wang2022), decreased Aβ42/40 ratio and increased total tau in CSF have been reported to be more useful biomarkers for a diagnosis of AD. The Aβ42/40 ratio has been suggested as a superior measure for the identification of AD pathology compared to concentrations of Aβ1-42 alone. Kanemoto et al. (Reference Kanemoto2023) found that the Aβ42/40 ratio was significantly lower and the total tau concentration was significantly higher in the CSF of iNPH patients who did not show an improvement on the tap test compared to those who did, even after adjusting for the degree and duration of iNPH symptoms. Among the triad symptoms of iNPH, the response in the cognitive domain, but not in the gait or urination domains, was associated with Aβ42/40 ratio. This is the first study to suggest that iNPH patients with concomitant AD pathology were less responsive to the tap test, similar to the association between shunt unresponsiveness and presence of AD pathology in iNPH, even after controlling for disease duration and symptom severity.
This study has several strengths. The total number of iNPH participants was relatively large. A few previous studies have reported an association between AD pathology and tap test responsiveness in iNPH, but the sample sizes were too small to allow for multiple comparison adjustment or multivariate analysis. The authors also point out some limitations to their study. As the concentrations of proteins in the CSF, including Aβ and total tau, have been reported to be different between iNPH patients and healthy subjects, the concentration of Aβ and total tau in the CSF of iNPH patients may not be the best biomarker for AD pathology. No cutoff values of CSF biomarkers to detect AD pathology in the authors’ laboratory were used and so, the exact results may not generalize to other labs. The effect of CSF removal is generally larger in a shunt surgery than in a tap test. Even in the iNPH group that did not improve with the tap test, improvement was seen after shunt surgery in a small proportion of the patients. It will be useful to follow the results of shunting in the patients with a negative tap test.
Appropriately, Kanemoto et al. conclude that the tap test should be used in considering shunt surgery in persons with iNPH, along with CSF biomarkers. The effect of AD comorbidity on tap test response in overall cognition was significant albeit small. Detailed neuropsychological evaluation for memory and frontal lobe function revealed a significant improvement even in those in whom the MMSE did not improve. Thus, a detailed cognitive test battery may be a useful tool to evaluate the cognitive response to a tap test, although the degree of cognitive improvement may be small in iNPH patients with low CSF Aβ42/40 ratio.
Thus, these three articles clearly help advance our understanding and management of patients with different types of dementias and suggest useful pathways to future research.
Conflict of interest
None.