精神症狀加速變成失智症


  【24drs.com】兩篇新研究確認,神經精神症狀(NPS)與輕微認知障礙(MCI)更快惡化成阿茲海默氏症(AD)有關。
  
  馬里蘭州巴爾的摩約翰霍普金斯大學博士候選人Sarah Forrester領導的第一篇研究明確指出,NPS和更快速惡化有關。舊金山加州大學R. Scott Mackin博士領導的第二篇研究認為,與腦部結構變化有關的慢性憂鬱症狀,可能會促使病情更快速轉化。
  
  Forrester表示,在臨床上,我們的研究讓醫師知道在實務上要注意哪些人,我們可以明確地指出哪些患者需要更多注意,高風險者可能適用一些預防策略,例如改善一般醫療狀況。
  
  這些研究發表於2月版的美國老年精神病學期刊。
  
  第一篇研究中,Forrester等人探討NPS和惡化成失智症的關聯,研究對象是「Alzheimer's Disease Cooperative Study (ADCS)」研究中、540名偶發MCI的患者,追蹤這些患者2年,每次訪視時,使用神經精神量表問卷評估這些患者。
  
  研究者使用隱藏分類分析將MCI患者根據有無出現各種NPS而分組,他們共分成三組NPS:嚴重組,高燥動率(84%)、焦慮(52%)、淡漠(51%)、夜間行為(48%)、去抑制(44%);情緒組,特徵是高憂鬱率(41%)、焦慮(31%)、易怒(32%)、夜間行為(35%);無症狀組,納入這組是因為不到5%的患者有所有症狀;每個類別的盛行率分別是7%、 37%和56%。
  
  在追蹤期間,121名(22%)患者被判斷已惡化成失智,419人(78%)依舊是MCI,有167人(31%)恢復到正常的認知。研究者報告指出,從MCI惡化到失智的比率,以嚴重組最高、情緒組居中、無症狀組最低。
  
  與無症狀組相比,嚴重組惡化成失智的風險超過2倍以上(風險比[HR]為2.69;95%信賴區間[CI]為1.12 - 2.70);情緒組惡化成失智的風險則是超過1.5倍(HR, 1.79;95% CI, 1.12 - 2.70)。
  
  Forrester等人在文章中指出,根據患者的症狀資料將他們分組,可以更加瞭解哪些症狀會造成失智診斷之風險改變、以及縮短惡化時間。冷漠和憂鬱在情緒組都很常見,這些症狀可能被證明是NPS群組的一部份,最能預測惡化。
  
  他們結論表示,對那些有NPS的人,我們的結果對於及早偵測和治療失智有所影響。因為有較多NPS和特定NPS的患者,更可能惡化成失智診斷,及早預防NPS或許有助於預防MCI和失智。
  
  第二篇研究中,Mackin博士等人檢視了慢性憂鬱症狀對於有惡化成失智之風險者的影響。
  
  他們使用「Alzheimer's Disease Neuroimaging Initiative」的資料檢視慢性憂鬱症狀、區域性腦萎縮和惡化成AD的關聯,研究對象是94名MCI患者,其中32人有慢性憂鬱症狀。
  
  研究者發現,慢性憂鬱症狀和額葉與前扣帶的皮質加速萎縮有關,已知這兩個區域會受到AD影響。
  
  在3年追蹤期間,38名患者(42.7%)惡化成AD,有慢性憂鬱症狀者的偶發AD比率高於沒有慢性憂鬱症狀者(62.1% vs 33.3%);至於有慢性憂鬱症狀者,惡化變成AD的時間比沒有憂鬱症狀者少60% (P = .008)。
  
  研究者指出,慢性憂鬱症狀和偶發AD之間的關聯,與顳葉區的皮質萎縮率無關,和額葉區域的皮質萎縮率有關。整體看來,研究結果認為,和腦部結構改變有關的慢性憂鬱症狀,可能會造成MCI更快速惡化成失智。
  
  編輯評論的共同作者、賓州匹茲堡大學精神病學教授、生物工程副教授Howard Aizenstein博士表示,這兩篇研究一起為更清楚說明MCI患者的情感症狀提供證據。
  
  Aizenstein博士表示,即便沒有失智風險之關聯,依舊建議充分治療情感症狀-但是,越來越多的證據認為,這或許可降低失智風險,為考量心智健康治療選項的患者提供更多資訊。
  
  這兩篇研究支持情感症狀和失智風險增加之關聯,但是都沒有確認因果關係。因此,我們不知道是否是情感症狀促成惡化為AD,也可能是潛在的神經退化變化導致情感症狀和失智。不過,似乎有著因果關係,因為情感症狀的多個路徑會惡化認知與功能,從而加快惡化成AD,因此,緩解情感症狀可能會降低失智症的風險。
  
  資料來源:http://www.24drs.com/
  
  Native link:Psychiatric Symptoms Speed Conversion to Dementia

Psychiatric Symptoms Speed Conversion to Dementia

By Megan Brooks
Medscape Medical News

Neuropsychiatric symptoms (NPS) are associated with more rapid progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), two new studies confirm.

The first study, led by Sarah Forrester, a doctoral candidate at Johns Hopkins University, in Baltimore, Maryland, pinpoints clusters of NPS associated with faster progression. The second study, led by R. Scott Mackin, PhD, University of California, San Francisco, suggests that chronic depressive symptoms are associated with structural brain changes that may contribute to more rapid conversion.

"Clinically," Forrester told Medscape Medical News, "our study gives clinicians an idea of who to keep an eye on in practice. We can definitively say which patients may deserve greater attention than others, and those in the higher-risk groups may be candidates for preventive measures, such as improvement in general medical health."

The studies are published in the February issue of the American Journal of Geriatric Psychiatry.

Predicting the Future

In the first study, Forrester and colleagues explored the association between NPS and progression to dementia in 540 patients with incident MCI from the Alzheimer's Disease Cooperative Study (ADCS). The patients were followed for a period of 2 years. At each visit, participants were assessed with the Neuropsychiatric Inventory Questionnaire.

The researchers used latent class analysis to classify MCI individuals into distinct subgroups on the basis of the presence or absence of different NPS. They identified three clusters of NPS: a severe cluster, marked by high rates of agitation (84%), anxiety (52%), apathy (51%), nighttime behaviors (48%), and disinhibition (44%); an affective cluster, characterized by high rates of depression (41%), anxiety (31%), irritability (32%), and nighttime behaviors (35%); and an asymptomatic cluster, labeled as such because all symptoms were endorsed by fewer than 5% of patients. The prevalence of each class was 7%, 37% and 56%, respectively.

During follow-up, 121 (22%) patients were judged to have progressed to dementia, 419 (78%) remained with MCI, and 167 (31%) reverted to normal cognition. The rate of progression from MCI to dementia was highest in the severe group, intermediate for the affective group, and lowest for the asymptomatic group, the researchers report.

Compared with the asymptomatic class, the severe class had more than twice the risk for progression to dementia (hazard ratio [HR], 2.69; 95% confidence interval [CI], 1.12 - 2.70); the affective class had more than 1.5 times the risk for progression to dementia (HR, 1.79; 95% CI, 1.12 - 2.70).

"Classifying patients based on their symptom profiles might allow a better understanding of how the addition of certain symptoms may change the risk of dementia diagnosis and shorten time to diagnosis," Forrester and colleagues note in their article.

Apathy and depression were common in both the affective and severe classes. "These symptoms may prove to be part of NPS clusters that are most predictive of progression," they write.

"Our results," they conclude, "have implications for early detection and treatment of dementia in those with NPS. Because patients with more NPS and specific NPS are more likely to progress to dementia diagnosis, preventing NPS earlier in life may be an avenue for prevention of MCI and dementia."

Brain Atrophy

In the second study, Dr Mackin and colleagues examined the role of chronic depressive symptoms in the risk for progression to dementia.

They used data from the Alzheimer's Disease Neuroimaging Initiative to characterize the relationship of chronic depressive symptoms, regional brain atrophy, and progression to AD in 94 individuals with MCI, 32 of whom had chronic depressive symptoms.

The investigators found that chronic depressive symptoms were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate, regions known to be affected by AD.

During median follow-up of 3 years, 38 participants (42.7%) progressed to AD. Incident AD was more common in those with than in those without chronic depressive symptoms (62.1% vs 33.3%). For patients with chronic depressive symptoms, the time to conversion to AD was 60% shorter than for those without depressive symptoms (P = .008).

The researchers note that the association between chronic depressive symptoms and incident AD was independent of cortical atrophy rates in the temporal regions but not of cortical atrophy rates in frontal regions. Taken together, the findings suggest that chronic depressive symptoms are associated with structural brain changes that may contribute to more rapid conversion to dementia in MCI, they conclude.

Causal Relationship "Likely"

Howard Aizenstein, MD, PhD, coauthor of an accompanying editorial, said that together, the two studies provide support for fully addressing affective symptoms in patients with MCI. Dr Aizenstein is professor of psychiatry and associate professor of bioengineering at the University of Pittsburgh, in Pennsylvania.

"Even without the link to dementia risk, full treatment of the affective symptoms would be recommended — but the accumulating evidence that this also may lower dementia risk provides additional information for patients in considering mental health treatment options," Dr Aizenstein told Medscape Medical News.

"These two studies support the association of affective symptoms with increased dementia risk. Neither study confirms causation; thus, we don't know if the affective symptoms potentiate the progression to AD. It could be that the underlying neurodegenerative changes lead to both the affective symptoms and dementia.

"However, it seems likely that there is a causal relationship, as there are multiple pathways in which affective symptoms can worsen cognition and function and thus hasten progression to AD. Thus, alleviating the affective symptoms may lower the dementia risk," he said.

The study authors and Dr. Aizenstein report no relevant financial relationships.

Am J Geriatr Psychiatry. 2016;24:105-106,117-125,126-135. Forrester et al,

    
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